Collagen-Based Products in Wound,Skin,and Health Care

Abstract

Collagen, the most abundant structural protein in the human body, plays a vital role in wound healing, tissue repair, and skin integrity. Collagen-based products—ranging from wound dressings, skin substitutes, dental and orthopedic scaffolds, to topical cosmetics and oral supplements—have proliferated rapidly across healthcare and consumer markets. Medical applications leverage collagen’s biocompatibility, biodegradability, and scaffold-forming properties to manage chronic wounds, burns, and bone defects, while emerging technologies such as recombinant collagen and phage-integrated dressings target future innovations. Topical collagen improves skin hydration but is unlikely to replace endogenous collagen; injectable fillers offer temporary cosmetic enhancement with some potential risks. Oral collagen supplements, although marketed for skin, joint, and hair health, primarily serve as incomplete proteins and require cautious interpretation, as rigorous clinical evidence supporting transformative outcomes remains limited. Specific formulations such as undenatured type II collagen show promise for inflammatory joint conditions by promoting immune tolerance. In wound care, collagen-based scaffolds enhance healing by supporting fibroblast proliferation, reducing inflammation, and modulating moisture balance, while novel crosslinked matrices and living skin equivalents push regenerative medicine boundaries. Not all collagen-based products are the same. As the global collagen market surges toward $18.7 billion by 2030, users must distinguish between marketing claims and evidence-based benefits of specific preparations. Proper product selection should be guided by clinical context, molecular source (animal, marine, recombinant), and intended use with awareness of underlying scientific evidence critical to therapeutic success. Continued innovation, rigorous validation, mechanism of action studies and rigorous clinical testing are essential to fully realize collagen’s therapeutic potential across medicine and wellness.

Keywords

collagen wound dressing market

Chandan K. Sen

SCOPE AND SIGNIFICANCE

This article provides an overview of collagen-based products spanning wound care, skin health, regenerative medicine, orthopedics, dentistry, and consumer wellness. It critically examines collagen’s biomaterial properties—biocompatibility, biodegradability, and scaffold-forming capacity—that underpin its widespread applications. Common collagen-based products are systematically categorized based on scientific levels of evidence, offering users an evidence-based framework to navigate a rapidly expanding market. The work highlights emerging innovations such as recombinant collagen, 3D-printed skin grafts, and phage-integrated dressings, while cautioning against unsupported marketing claims. This work is not intended to be a systematic review. This is specifically a critical review (note peer-review process in Acknowledgments). While briefly noting key milestones in product development, the focus remains on technological trends, biomolecular sources, and functional advances. Projected to drive a $18.7 billion global market by 2030, collagen’s future hinges on rigorous validation, innovation, and responsible translation.¹ Serving health care providers, researchers, manufacturers, and informed consumers alike, this article delivers a critical, science-grounded roadmap to understanding collagen’s evolving impact across medical, cosmetic, and biotechnology sectors.

TRANSLATIONAL RELEVANCE

Collagen, the dominant structural protein in the human body (25–30% of total body protein), has been incorporated into a multitude of medical devices designed for wound healing, tissue regeneration, and skin care. Collagen can easily be isolated from animal, plant and marine sources, as well as be produced in a laboratory synthetically or as recombinant protein (Fig. 1). The abundant accessibility and ease of use in clinical applications has led to a global market of patient-accessible products that promote positive healing outcomes compared with more traditional approaches.

Figure 1.

Collagen sources. Collagen is a protein abundantly available from a variety of sources. Collagen can easily be isolated from animal, plant, and marine sources. Collagens can also be produced in a laboratory synthetically or as yeast/fermentation-derived recombinant protein.

CLINICAL RELEVANCE

This article delivers critical insights for health care providers utilizing collagen-based products in clinical and wellness practice. It sketches the biological roles of collagen in wound healing, skin regeneration, orthopedic repair, and dental reconstruction, emphasizing how product-specific properties—such as molecular structure, source, crosslinking, and bioactivity—affect clinical outcomes. By categorizing commonly used collagen products according to levels of scientific evidence, the work offers an essential guide for evidence-based product selection. It highlights the importance of matching the product’s mechanism of action—such as scaffold support, moisture balance, matrix metalloproteinase inhibition, or antimicrobial enhancement—to the patient’s wound type and healing phase. Furthermore, it addresses emerging challenges such as biofilm resistance, impaired vascularization, and chronic wound recurrence, suggesting collagen innovations that may overcome these barriers. Health care providers are encouraged to critically evaluate marketing claims, understand product-specific risks, and prioritize products validated by rigorous clinical trials to optimize patient outcomes.

WOUND HEALING AND CARE

Collagen is the most abundant protein in the human body (25–30% total protein). There are at least 28 types of collagens of which over 90% of the collagen in humans is type I & III. Collagen-based products have proven beneficial, with utility spanning a range of products from medical devices to cosmetic and food applications. In 1981, Collagen Corporation (later Integra LifeSciences), launched CollaDerm, one of the first commercial collagen wound dressings with pre-marketing approval. In 1985, Johnson & Johnson introduced Instat, a collagen sponge indicated for hemostasis.² In 1996, Integra LifeSciences introduced Integra Dermal Regeneration Template (collagen-GAG matrix for burns and complex wounds).³ In 1997 Smith & Nephew released Biostep (collagen-alginate dressing for moist wound healing). In 2000, SouthWest Technologies launched ColActive bovine collagen wound dressing. In 1998 and 2002, Johnson & Johnson received FDA approval for Fibracol (collagen-alginate wound dressing) and Promogran (collagen-oxidized regenerated cellulose matrix for chronic wounds), respectively (originally developed by J&J, now manufactured and sold by Solventum).⁴ These products represent several historical examples showing progressive developments in collagen-based product development. An increasing demand for these products is showing economic impact at the U.S. and global scales. In 2024 U.S. collagen market reached $2.5 billion USD (Global $9.9 billion) and, with compound annual growth rate (CAGR) of 12.9%, is estimated to reach $4.94 billion USD by 2030 (Global CAGR 11.3%, $18.7 billion).¹ Collagen dressings and scaffolds are currently used to manage chronic wounds such as diabetic ulcers, venous stasis ulcers, and pressure ulcers. Useful collagen-based products seem to support wound care by providing a scaffold or matrix for new tissue growth, reducing inflammation, and helping maintain a moist wound environment. This work evaluates the state of scientific evidence on the most common collagen-based products in the market.

Wound care

Wound healing can be defined by four chronological, overlapping phases that include hemostasis, inflammation, proliferation and maturation.^5,6 The hemostasis phase of wound healing consists of platelet hemostatic plug formation and fibrin crosslinking that creates a clot to prevent bleeding.⁷ This response is immediate and can last hours depending on wound size and depth. Once the wound opening has been plugged, initial inflammatory response activates and recruits immune cells, such as neutrophils and macrophages, that in turn, recruit fibroblasts, epithelial and endothelial cells from surrounding tissues through proinflammatory cytokine release.⁸ This initial inflammatory response occurs within hours and may last for days while infection surveillance and removal of bacteria and necrotic tissue is performed. Breached skin barriers allow for the introduction of microorganisms that can begin colonizing the wound surface, without impeding wound healing. However, if bacteria reach critical colonization, wound healing is hindered without triggering acute inflammation. A wound is considered infected when colony counts reach 100,000 organisms per gram of tissue per milliliter of fluid.⁹ Compared with acute wounds, chronic wounds that have been infected are often complicated by a chronic inflammatory response that can disrupt subsequent stages of wound healing and result in impaired wound closure.¹⁰ Overlapping with the resolution of the initial inflammatory phase, the proliferation phase expands and drives the activities of recruited fibroblasts, epithelial and endothelial cells, lasting on a scale of days to weeks.⁵ Fragments from degraded collagen promote infiltrating fibroblast proliferation, deposition of collagen and extracellular matrix (ECM) components during granulation tissue formation. Fibroblast-like cells, originating from wound-macrophages, populate the granulation tissue.¹¹ Immune cells also contribute through the release of growth factors that promote keratinocyte re-epithelialization and endothelial cell angiogenesis programs.¹² The maturation phase of wound healing regulates ECM remodeling, which occurs during new ECM synthesis where fibroblasts, endothelial and epithelial cells release matrix metalloproteases (MMPs) that balance this process with degradation activity.¹³ This balance ultimately defines the barrier functionality and tensile strength of healed skin, which due to differences in glycosylation and organization, can only reach up to 80% of original tissue maximum.¹⁴ Hypertrophic and keloid scars form as this balance shifts toward excessive ECM formation and fibrosis, which continues to undergo remodeling for months or years after wound closure. During the process of wound healing and ECM remodeling, relative abundance of collagen I and collagen III change to support different biological processes. In early wound healing, collagen III is more prevalent to support the inflammatory and proliferative phases. Collagen I, however, becomes more prevalent than collagen III as the wound progresses through ECM remodeling in the late stages of wound healing.¹⁵

Collagen synthesis is a tightly regulated biochemical process that begins with transcription of pro-α1 and pro-α2 chains and translation to pre-pro-polypeptide chains.¹⁶ These chains undergo N-terminal cleavage, lysine and proline hydroxylation, and glycosylation post-translational modifications in the rough endoplasmic reticulum, necessary for the assembly of the procollagen triple helix structure.¹⁷ Processing continues in the Golgi apparatus where procollagen is packaged into vesicles before secretion into extracellular space. Collagen peptidases then cleave the ends of procollagen to produce tropocollagen.¹⁸ Lysyl oxidase facilitates subsequent tropocollagen molecule cross-linking to form collagen fibrils.¹⁹ Molecular oxygen incorporation into nascent collagen is a critical step for collagen escape to extracellular space and proper maturation that provides tensile strength.²⁰ In ascorbate insufficient conditions (e.g., scurvy) collagen molecules do not undergo post-translational hydroxylation by prolyl hydroxylase and lysyl hydroxylase and fail to mature, resulting in weakened vessel formation during angiogenesis and impaired wound healing.^20,21

Wound care is often complicated by factors associated with disease states and comorbidities. For example, diabetes is associated with peripheral arterial disease (PAD), a peripheral vascular disease, that is present in 7–12 million individuals in the United States with a prevalence disproportionately affecting black American patients.²² PAD can result in ischemic peripheral tissues that experience tissue loss, ulcers, and gangrene.²⁰ Venous insufficiency, another peripheral limb ulcer-inducing condition, is a result of inflammatory-induced changes in venous walls and valves that cause retrograde blood flow. Interrupted blood flow in capillaries from hypervolemia or hypertension in veins can cause peripheral edema, deoxygenated venous blood pooling under the skin, venous ischemia and venous hypoxia. Subsequent skin damage in these areas can result in venous leg ulcers (VLUs).²³ These hypoxic conditions are detrimental to wound healing. Hypoxia in wounds can be mild-modest to near-anoxic depending on factors restricting O₂ supply and lead to chronic non-healing or stalled wounds.^24,25 Chronic wounds in the United States continue to be a significant health care burden, affecting upwards of 10.5 million Medicare beneficiaries, and are a major contributing factor to lower extremity amputations.^26,27 Lower extremity amputation mortality rates at 1- and 10-year follow-ups reached staggering rates of 33.7% and 80%, respectively.²⁸

Acute moderate hypoxia, but not severe hypoxia, in wound beds stimulate healing through pro-angiogenic hypoxia inducible factor-1 and vascular endothelial growth factor (VEGF) signaling.²⁰ Severe near-anoxic hypoxia, however, leads to stalled wound healing by downregulating cell signaling and angiogenesis, inhibiting aerobic glycolysis that is required to meet the energy demands of a healing wound as well as by inhibiting collagen synthesis.^20,29,30 Oxygen supply is required for stages of collagen deposition, polymerization, and maturation that are necessary structural components for new capillary tube formation during angiogenesis.^31,32 With poor collagen deposition, weak tensile strength, and immature vessel formation, stalled wound healing exposes the wound bed to greater risk of infection and subsequent complications. Collagen-based dressings can be utilized to improve healing outcomes in ischemic wounds. In recent porcine ischemic full-thickness excisional wound studies, application of a modified collagen gel (MCG) induced monocyte chemoattractant protein-1-1 and VEGF expression, resulting in more endothelial cell infiltration and vascularization during healing.³³ Specifically, the MCG increased the initial transitory inflammation response, proliferative phase, angiogenesis and tissue maturation during remodeling, which showed improvement in three of the four phases of wound healing (inflammation, proliferation, maturation).³⁴ Mechanistically, a MCG dressing improved anti-inflammatory signaling through interleukin (IL)-10 production via the cytokine regulating miR-21-c-Jun N-terminal kinase pathway, increased the ratio of anti-inflammatory/pro-inflammatory macrophage polarization, and promoted angiogenesis through VEGF expression.³⁵ The microRNA miR-200 family has been implicated in hypoxia and ischemic tissue damage.³⁶ In an in vivo diabetic wound healing animal model, topical tissue nanotransfection of anti-miR-200b oligonucleotide promoted therapeutic tissue vascularization with significantly increased collagen deposition at the ischemic wound site.³⁷

Microbes infecting an open wound have the potential to develop a planktonic (free-living) infection, or they may form a polymicrobial aggregate known as biofilm.³⁸ Biofilm aggregates are able to adapt to their environment, as well as evade host immune cells and antimicrobials due to a protective extracellular polymeric layer.³⁹ Treatment of infected wounds is typically a combination of standard of care debridement and topical antimicrobials (such as hypochlorous acid) used in conjunction with systemic antimicrobial therapy. However, the resistant/evasive nature of biofilms coupled with an inability to easily visualize them results in high rates of biofilm recidivism. Biofilm infection not only contributes to open wound chronicity but also undermines the structural integrity of collagen as wound closure occurs. S. aureus biofilm infection, for example, represses miR-143, resulting in an upregulation of collagenolytic matrix metalloproteinase-2 and subsequent degradation of collagen type I as the wound heals. This results in a wound that achieves visual closure; however, the compromised tensile integrity of the newly formed skin means that the wound is likely to recur, seemingly spontaneously over time.⁴⁰ The transepidermal water loss study performed by the NIDDK Diabetic Foot Consortium shows that wounds that close without re-establishing barrier function are likely to recur.^41,42 With 78.2% of chronic wounds showing signs of biofilm infection, identifying or synthesizing wound dressings that not only promote wound healing, but also eradicate biofilms, is a high priority in wound care. The use of biomaterials, including collagen-based dressings and scaffolds, has been beneficial in treating chronic wounds due to their biocompatibility and biodegradability, as well as properties that promote fibroblast infiltration and proliferation.⁴³ Stabilized pericardial collagen matrix, a cross-linked stabilized acellular equine pericardium-derived collagen matrix dressing, has been mechanistically shown to recruit macrophages to wounds and upregulate antimicrobial peptide human keratinocyte β-defensin (HDB-1) during wound healing, as well as calgranulin S100A9. HDB-1 protects the wound from microbial growth by directly disrupting bacterial membranes while S100A9 suppresses bacterial and fungal growth and recruits phagocytic immune cells to the site of injury.⁴⁴

Collagen-based dressings

Collagen serves as the principal structural ECM protein in the skin, tendon, and bone.⁴⁵ The most common collagen types (I–V) are differentially expressed within various tissues throughout the body: collagen I primarily in skin, tendon, bone, muscle, heart, lungs, and vessels; collagen II in cartilage; collagen III in vessels uterus and bowel; collagen IV in basement membranes; and collagen V in hair and nails.^15,46 Because of its biocompatibility, biodegradability, and low immunogenicity, collagen has been used as a biomaterial for a wide range of applications. Collagen has been incorporated into products used for wound dressings, dental surgery, orthopedics, tissue engineering, pharmaceutical therapeutics, as well as food and cosmetic products (Fig. 2).⁴⁷ Traditional dressings composed of inert materials, such as cotton gauze, provide a passive protective barrier to prevent environmental debris and contamination from entering a wound. These dressings provide a layer of protection to promote healing and minimize risk of infection; however, they also have poor absorptive properties and moisture regulation that can cause wounds to dry out or dressings to adhere to wound and result in the need for frequent dressing changes.⁴⁸ Alternatively, semi-permeable wound dressings can adhere tightly to wounds to confine wound exudates and maintain a moist and oxygenated wound healing environment.^48,49 While semi-permeable polyurethane-based dressings permit oxygen, carbon dioxide, and water vapor to pass through, they do not have moisture absorption or MMP neutralizing properties, thus limiting their most effective application to acute wounds and pressure ulcer prevention.⁵⁰ Managing wound exudates, moisture control, MMP neutralizing activity, biocompatibility, low immunogenicity, biodegradability, and antimicrobial activity are desirable properties in wound dressings that have prompted advances in dressing innovation and the development of collagen, alginate, elastin, hyaluronic acid (HA), and chitosan-based bioactive dressings, as well as living skin equivalents.^51–56 Bioactive dressings are often combined with synthetic, chemical, or metallic antimicrobial agents to prevent wound infection during the healing process, which can be essential in the treatment of chronic slow-healing wounds.⁵⁷ Collagen-based bioactive wound care products have been developed for a multitude of applications and come in a variety of forms including dressings, sponges, gels, cross-linked hydrogels, powders, acellular scaffolds, and skin-like substitutes.

Figure 2.

Collagen devices. Collagen, both native and hydrolyzed (image inset), has been used in a multitude of clinical products and devices. These products have shown positive outcomes in patients with regard to wound healing, cardiovascular regeneration, orthopedic repair, dental plugs and regeneration, dietary supplementation, and cosmetic implant and augmentations.

Collagen, as the primary structural protein in extracellular matrices, serves as a base material for wound dressings that are biocompatible, low antigenic, nontoxic, and biodegradable.⁵⁸ Collagen can be sourced from animals, plants or produced as recombinant protein, with porcine collagen being most similar to human collagen. Other animals commonly sourced include bovine, equine, ovine, rodent, poultry, and various marine animals.^59–62 Air-drying or freeze-drying collagen can produce collagen film dressings that easily adhere to wounds and can promote keratinocyte proliferation and epidermal remodeling.⁶³ These films can be combined with growth factors, drugs, or nanoparticles for the slow-release treatment of wounds. However, collagen films are restricted for use on smaller wounds as excessive exudate and leakage can lead to pathogenic infiltration and infection.⁶⁴ Freeze-drying is also used to make collagen sponges that are porous scaffold materials, which retain mechanical strength, plasticity, and absorptive properties.⁶⁵ Collagen sponge properties are arguably more suitable for chronic wounds, dental applications, ulcers, and full-layer burn wounds with high levels of exudate as they are highly absorptive without adhering to wound beds. Native fibrous collagen matrix membranes have been utilized as guided bone regeneration dressings because of claimed better mechanical and osteoinductive properties than collagen sponges.⁶⁶ Collagen membranes combined with growth factors can promote an osteogenic environment that promotes horizontal bone augmentation and regeneration.⁶⁷ With similar activity, collagen plugs have been developed to guide bone regeneration following tooth extractions. Placed in the extraction socket, collagen plugs stabilize blood clots and support an osteogenic environment that can be further promoted with the addition of autologous bone chips.⁶⁶

Crosslinked collagen hydrogels may provide a transparent semi-permeable scaffold with high moisture content to possibly promote wound healing and necrotic tissue autolysis debridement.^68–70 Nonadherence to the wound prevents tissue agitation and damage when the dressing is replaced. Additional crosslinking with HA and chitosan can improve the hydrogel water retention and bacterial barrier function, while also promoting cell migration, proliferation, and adhesion.⁷¹ Collagen hydrogels, like other collagen dressings, can be combined with antibacterial peptides or growth factors to prevent bacterial growth and promote angiogenesis, granulation tissue formation, and tissue regeneration.^72–74

Granulated or powdered hydrolyzed collagen, unlike hydrogels, tends to have minimal crosslinking and can vary in particle size based on methods of preparation (Fig. 3).⁷⁵ Collagen powders can be packed into ulcers, second-degree burns and wounds where they absorb exudate, control minor bleeding, and form a gel-like barrier that protects a moist wound environment.⁵ Collagen powders, similar to hydrogels, can be used as drug delivery systems that are activated upon contact with the wound where high surface area ratio lends rapid delivery for treatments.⁷⁶

Figure 3.

Intact versus hydrolyzed collagen. Intact collagen contains substantial crosslinking necessary for the structural support network it forms in the extracellular matrix. Hydrolyzed collagen peptides (often in granulated or powder products) tend to have minimal crosslinking and can vary in size based on methods of preparation. Receptors on fibroblasts and macrophages can bind hydrolyzed or degraded collagen peptides, which signal for proliferation, infiltration, and immune responses necessary in the wound healing process.

In addition to collagen being used as a bioactive dressing, acellular collagen scaffolds and living skin equivalents are also being utilized as effective skin graft substitutes. Decellularized fish skin, for example, is structurally similar to mammalian skin and exhibits high biocompatibility, porosity, absorptive capacity, biodegradability, and low immunogenicity.⁷⁷ Decellularized marine collagen appears to offer a notable advantage over mammalian-derived collagens by exhibiting a reduced risk of disease transmission when used as a graft in human patients.^78–81 Decellularized collagen grafts from marine or mammalian sources have a structural advantage in the treatment of full thickness wounds and soft tissue augmentation with positive outcomes in thousands of clinical cases dating back to the mid-1990s.⁸² Living skin equivalents are being designed to treat similar severe wounds through tissue engineering. Using a collagen gel, sponge, scaffold, or hydrogel as a common starting material, living skin equivalents are seeded with autologous (patient-derived) or allogenic (neonatal or newborn foreskin-derived) fibroblasts and keratinocytes to create a biocompatible dermal graft equivalent.⁵⁶ These living skin equivalents are applicable to deep wounds where collagen sponges and membranes are insufficient, including diabetic ulcers, venous ulcers, full-thickness burns, and other skin replacement procedures. Decellularized collagen scaffolds are also being used in the development of biological medical devices for hernia and heart valve repair.^83–88

The collagen-based wound care market is evolving rapidly, with several innovative products in the pipeline leveraging advanced biomaterials, bioengineering, and antimicrobial technologies. Rigorous clinical studies are required as new products advance to the market. CollPlant (Israel) is developing rhCollagen (recombinant human collagen) from tobacco plants, expected to enter advanced wound care applications (e.g., 3D-printed skin grafts).⁸⁹ Potential benefits include lower immunogenicity, scalable production, and no animal-derived risks. Yeast/fermentation-derived collagen are under development for the wound care market. Companies such as Geltor (United States)⁹⁰ and Jellatech (Denmark)⁹¹ are working on biosynthetic collagen for medical use, including wound dressings. Phage-integrated collagen comprises bacteriophage-infused dressings designed to target pathogens such as MRSA and Pseudomonas. These dressings are currently in clinical trials by Nextbiotics & Adaptive Phage Therapeutics. In addition, companies such as Pandorum Technologies (India)⁹² are developing 3D-printed collagen-based corneas, while Poietis (France)⁹³ is testing 3D-printed collagen-based living skin for the treatment of burns and chronic ulcers. Drug-eluting collagen dressings are in the pipeline. Platelet-derived growth factor/VEGF-loaded collagen (similar to Regranex but cheaper) are in development by Helix Biomedix.

REGENERATIVE MEDICINE

Regenerative medicine⁹⁴ is a rapidly developing field in health care. This evolving field of study harnesses cells, scaffolds, gene delivery, or their combination to heal damaged or diseased tissue back to their native functional state.⁹⁵ Since the first U.S. FDA approved skin substitute came to market in 1997, tissue engineers have developed multiple approaches to treat a variety of wounds, from mild and severe burns to abrasions and lacerations. While mild wounds may heal in days, severe wounds or wounds with complications from underlying disease or infection require the assistance of a scaffold structure capable of maintaining a moist wound environment, as well as modulating the phases of healing to bring complete closure. Collagen has come to the forefront of many approaches because of its biocompatibility, bioactivity, and low antigenicity.⁵⁸ Often used as a wound dressing, collagen-based products come in sheets, powders, and hydrogels, among others (Tables 1–6).

Table 1.

Level of evidence 1

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action (MoA)	Outcomes study/Trial	References
AlloDerm LifeCell Corporation	Aseptic decellularized human dermal matrix; two forms: freeze-dried or ready to use; contains collagen, elastin, and laminin	Level 1 Level 4 Level 7a	Human skin allograft that has had epidermic and cells removed to prevent tissue rejection	Indicated for soft tissue repair; breast implant reconstruction following mastectomy; skull base reconstruction; periodontal surgeries, dural replacements in neurosurgery, abdominal hernia, head, and neck.	Low levels of fibroblast and blood vessel infiltration compared with other acellular dermal matrices; initial infiltrate of inflammatory macrophages, followed by proliferative phase where endothelial cells can promote revascularization in 7 days (subcutaneous models)	AlloDerm patients showed higher risk of infection and more unplanned operating room visits than other acellular dermal matrices (ADMs)	^96–101
Apligraf ■ Organogenesis Inc.	Bovine type I collagen matrix cultured with allogeneic male neonatal fibroblasts and keratinocytes	Level 1 Level 3 Level 5 Level 7b	Full-thickness skin equivalent used to treat chronic diabetic and venous ulcers; temporary biological dressing, providing growth factors to the wound	Indicated for use with standard therapeutic compression for the treatment of noninfected partial and full thickness skin ulcers due to venous insufficiency of >1 month duration and which have not adequately responded to conventional ulcer therapy	Apligraf application invokes an inflammatory response which is essential for acute wound healing; possibly reverts the chronic inflammatory response in nonhealing wounds to a beneficial acute inflammatory signaling response; hypothesized mechanisms include Apligraf secreting growth factors and cytokines of the prohealing pathways, stimulating venous leg ulcer (VLU) cells to activate healing pathways, or a combination of the two	The use of Apligraf in conjunction with compression therapy is a safe and effective way to treat VLUs; patients were twice as likely to achieve complete wound closure by 6 months, and over 60% more effective in achieving wound closure than active control	^102–112
Biodesign (BioD) ■ Cook Biotech.	Acellular porcine small intestinal submucosa (SIS); contains ECM collagen, glycosaminoglycans, proteoglycans, and glycoproteins	Level 1 Level 4 Level 5 Level 7a	Creates an environment that allows cells in the body to secrete growth factors and replicate; as the body heals, SIS is gradually remodeled and integrated into the body, leaving behind organized tissue that provides long-term strength	Implantation to reinforce soft tissue; chordee correction; Peyronie’s disease; urethral repair; anorectal fistula repair reinforcement, rectal prolapse/rectal intussusception repair; ventral and hiatal hernia repair; dura mater graft; duraplasty graft; tympanic membrane perforation closure	Reduces profibrotic gene and protein expression (thrombospondin-1 and fibronectin-1) in fibroblasts; reduces levels of latent transforming growth factor which, in combination with fibronectin-1 downregulation, suggests a mechanism with which BioD scaffolds hinder normal and keloid fibroblast profibrotic responses during tissue repair	Laparoscopic paraesophageal hernia repair patients had long and durable relief of symptoms and improvement in quality of life with SIS; SIS myringoplasty yielded reduced surgical time with no adverse events	^113–120
Bio-Gide □ Geistlich Pharma AG	Bilayer noncrosslinked porcine collagen membrane with a dense film layer to prevent soft tissue invasion	Level 1 Level 4 Level 5 Level 7a	Collagen membrane for reliable bone regeneration and optimal tissue integration; permits prompt and homogeneous vascularization and so brings about optimal tissue integration and wound stabilization; intended to be used in the treatment of hard and soft tissue defects in oral and maxillofacial surgery	Augmentation around implants placed in immediate or delayed extraction sockets; localized ridge augmentation for later implantation; alveolar ridge reconstruction for prosthetic treatment; filling of bone defects after root resection; cystectomy, removal of retained teeth, guided bone regeneration in dehiscence defects; filling peridontal defects; elevation of the maxillary sinus floor; filling of peri-implant devices; can be used in combination with a void filler, such as Bio-Oss Collagen	Collagen fibers provide an osteophilic matrix that guides bone towards the center of a defect; intrafibrillar mineralization of collagen fibrils occurs spontaneously and presumed independent of osteoblast activity	Long-term data over 12 to 14 years show predictable results of bone augmentations; Bio-Gide use resulted in lower occurrence of wound dehiscence than control; Bio-Oss Collagen and Bio-Gide together limit the loss in alveolar ridge dimensions following tooth extraction	^121–132
Bio-Oss Collagen □ Geistlich Pharma AG	90% Bio-Oss natural bone mineral granules and 10% porcine collagen type I	Level 1 Level 4 Level 5 Level 6b	Designed to stabilize clots, promote bone regeneration, and improve bone quality; intended to be used in the treatment of hard tissue defects in oral-maxillofacial surgery.	For augmentation or reconstructive treatment of the alveolar ridge: filling of periodontal defects; filling of defects after root resection, apicoectomy, and cystectomy; filling of extraction sockets to enhance preservation of the alveolar ridge; elevation of the maxillary sinus floor; filling of periodontal defects in conjunction with products intended for guided tissue regeneration (GTR) and guided bone regeneration (GBR); filling of peri-implant defects in conjunction with products intended for GBR	MoA was not directly stated in peer-reviewed literature. Company claims Bio-Oss Collagen promotes rapid vascularization and epithelial regeneration, as well as encouraging bone regeneration.	Prospective 10-year follow-up demonstrated that the great majority of the implants maintained successful soft tissue health and dimensional buccal stability; Bio-Oss Collagen and Bio-Gide together limit the loss in alveolar ridge dimensions following tooth extraction	^{123,133–141}
CellerateRX Surgical Powder □ Sanara MedTech	Hydrolyzed type I bovine collagen	Level 1 Level 2 Level 5 Level 7a	Hydrolyzed collagen fragments do not have to be broken down by the body before use; soluble; compatible with negative pressure wound therapy	Intended for surgical wounds, traumatic wounds, partial and full thickness wounds, and first- and second-degree burns	CellerateRX differentially induced phagocytosis, efferocytosis, and reactive oxygen species (ROS) production in murine wound macrophages at early and late phases of the inflammatory response; potentiated proinflammatory and anti-inflammatory cytokines at appropriate stages of wound healing; improved wound perfusion and closure; improved the quality of wound healing by improving breaking strength of the closed wound tissue; this predicts fewer wound recurrence in CellerateRX-treated wounds	CellerateRX powder appears to attenuate postoperative lymphorrhea and blood loss in patients; suggests benefits for high-risk patients and blood loss complications	^142–152
EpiFix □ Mimedx	Dehydrated human amnionic/chorionic membrane (dHACM) tissue graft that contains extracellular biomacromolecules including collagen type IV, V, VII, proteins, fibronectins, laminins, proteoglycans, and GAGs	Level 1 Level 3 Level5 Level 7b	Processed via a PURION, a patented approach that preserves the ECM and regulatory proteins while removing the contaminants in the blood through a proprietary cleansing procedure	Placental tissue allograft available in sheet and mesh/fenestrated configurations in a variety of sizes to reduce wastage; indicated for acute and chronic wounds, debridement, dehisced wounds, diabetic foot ulcers, venous leg ulcers, pressure ulcers, Mohs repair	Fibroblast and keratinocyte infiltrates are presumed to result in paracrine signaling to support angiogenesis, tissue homeostasis, as well as regulated cytokine and growth factor expression to facilitate wound healing	Subjects treated with EpiFix had a significantly higher probability of complete healing within 12 weeks versus without EpiFix; results confirm the advantage of EpiFix allograft as an adjunct to multilayer compression therapy for the treatment of nonhealing, full-thickness venous leg ulcers	^{102,153–159}
Fibro-Gide® □ Geistlich Parma AG	Type I/III porcine volume stable collagen matrix	Level 1 Level 4 Level 5 Level 7a Level 7b	Intended to be used as an implantable device for regeneration and augmentation of soft tissue in oral and maxillofacial surgery.	For soft-tissue augmentation; localized gingival augmentation to increase KT around teeth and implants; alveolar ridge reconstruction for prosthetic treatment; recession defects for root coverage	Has mechanical properties appropriate to withstand the mechanical stresses that occur after wound closure in soft-tissue augmentation procedures, i.e., it has good volume stability and it withstands early resorption to allow the formation of new soft-tissue and degrades over time; the matrix is designed with an appropriate thickness to provide sufficient space for the ingrowth of new soft-tissue; the device becomes well integrated into the surrounding soft-tissue	Data show soft-tissue thickening around dental implants (1–2 mm gain buccally, 0.68–1.68 mm vertically); the augmented volume is stable in the long run (5-year data); morbidity is lower and surgery time is shorter than with using an autologous graft; used around teeth (single and multiple recessions), Fibro-Gide improves root coverage and gingival thickness	^160–169
Hemopatch □ Baxter International Inc.	Synthetic, protein-reactive monomer and a collagen backing	Level 1 Level 3 Level 4 Level 5 Level 6a Level 7a	Absorbable collagen pad intended for wound sealing and hemostasis	Hemostatic device and surgical sealant for procedures in which control of bleeding or leakage of other body fluids or air by conventional surgical techniques is either ineffective or impractical; used to close dural defects following traumatic injury, excision, retraction, or shrinkage of the dura mater	When placed on a wound with blood, or other bodily fluids, the hydroxysuccinimide functionalized polyethylene glycol (PEG) becomes activated and hydrolyzed, resulting in covalent amide bonding/affixing between the patch collagen, PEG, and tissue	Hemopatch is demonstrated to be an effective, easy-to-use hemostatic agent in open and minimally invasive surgery of patients with thrombin- or platelet-induced coagulopathies.	^170–182
Mucograft and Mucograft Seal (EU MDR) □ Geistlich Pharma AG	Type I/III porcine collagen matrix	Level 1 Level 3 Level 4 Level 5 Level 7a Level 7b	Faster soft-tissue wound healing compared with autologous grafts; creates predictable soft-tissue dimensions for later soft-tissue management and allows for flexible timing of implant placement; to be used in closed and open healing situations to close wounds of oral mucosa and support wound healing and regeneration processes in case of oral mucosa defects and deficiencies	Covering of implants placed in immediate or delayed extraction sockets; localized gingival augmentation to increase keratinized tissue around teeth and implants; alveolar ridge reconstruction for prosthetic treatment, and recession defects for root coverage	Bilayer collagen structure where mechanism is based on porosity; low-porosity porcine peritoneum-derived layer maintains elastic strength for mucosal suturing; high-porosity porcine skin-derived layer permits tissue adherence, promoting bone-forming cells and tissue growth while also stabilizing blood clot; host tissue infiltrates begin depositing ECM 3 days postimplant; infiltrating macrophages are attributed to degrading the implanted matrix over time	At 6 postoperative months, the computed tomography showed that the bone volume was maintained; it is concluded that Geistlich Mucgraft Seal and Geitlich Bio-Oss are materials that can be used as an excellent possibility of maintenance of the socket structure, postexodontia	^82,183–197
OASIS Wound Matrix □ Smith & Nephew	Porcine type I/III collagen; SIS wound matrix dressing	Level 1 Level 5 Level 7b	Support normal physiological functions via facilitating dermal cell infiltration; used in a variety of settings, including long-term, outpatient, and at-home care; naturally derived structure that supports healing process; incorporated and absorbed into the wound.	Management of wounds including partial- and full-thickness wounds, pressure injuries, venous ulcers, chronic vascular ulcers, tunneling and undermining wounds, diabetic ulcers, trauma wounds (abrasions, lacerations, second-degree burns, skin tears), draining wounds, and surgical wounds (donor sites/grafts, post-Mohs surgery, postlaser surgery, podiatric, wound dehiscence).	Contains GAGs that stimulate angiogenesis, inhibit coagulation, organize collagen deposition, promote differentiation and proliferation; matrix absorbs and protects albumin, heparin, fibronectin, FGF-2, and PDGF to promote infiltration of fibroblasts, vascular endothelial cells, neutrophils, and macrophages to the injured area	Wound closure (55%) in comparison with SOC (34%); 7 of 13 wounds closed fully after 12 weeks.	^198–204
Omnigraft Dermal Regeneration Matrix/Integra Dermal Regeneration Template (IDRT) ■ Integra LifeSciences	Bovine type I collagen/chondroitin-6-sulfate sponge with thin silicone layer on the epidermal surface	Level 1 Level 2 Level 5 Level 6b Level 7b	Provides an environment for new skin and tissue to regenerate and heal diabetic foot ulcer (DFU) wounds	Postexcisional treatment of life-threatening full-thickness or deep partial-thickness thermal injuries; repair of scar contractures; and treatment of partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care	MoA was not directly stated in peer-reviewed literature. Company claims that this two-layer skin regeneration product offers controlled pore size, porosity, and degradation rate allowing for cellular infiltration, neovascularization, and dermal regeneration while the semi-permeable silicone layer provides epidermal-like protection and moisture control	In RCTs with life-threatening burns, patients treated with IDRT needed thinner skin grafts, causing the donor site to heal sooner; patients with pediatric burns treated with IDRT scored better on multiple physiological markers and had better cosmetic outcomes than patients treated with the standard autograft-allograft technique; patients with DFU showed decreased the time to wound closure, improved components of quality of life, and had less adverse events compared with standard of care	^205–212
Promogran Matrix □ Johnson & Johnson	Collagen matrix; 55% bovine collagen and 45% oxidized regenerated cellulose (ORC)	Level 1 level 4 level 5 Level 7b	Oxidized regenerated cellulose and bioactive collagen product that binds to and neutralizes destructive proteases in chronic wound fluid; Reduction of MMP burden in the chronic wound allows endogenous ECM protein cells to proceed to the formation of granulation tissue and normal wound healing	In the presence of exudate, Promogran matrix transforms into a soft, confirmable, biodegradable gel, and thus allows contact with all areas of the wound; the dressing helps create a moist wound bed and an environment that supports wound healing; indicated for non-necrotic chronic wounds without infection including venous and arterial leg ulcers, pressure ulcers, and DFUs	Absorbs wound exudate liquid, forming a biodegradable gel that inhibits MMPs and promotes wound healing; the wound conforming gel binds and protects growth factors in an active state, that are steadily released back into the wound as the collagen matrix is degraded; collagen and oxidized regenerated cellulose bind and inhibit proteases detrimental to the healing process, including MMPs, elastase, and plasmin, likely through steric hinderance	While positive clinical outcomes have been observed, limited evidence exists, and future research is necessary to validate potential clinical and economic benefits	^213–222
Therapeutic Nutrition Powder Juven	L-glutamine, L-arginine, citric acid, hydrolyzed beefcollagen, sugar, calcium beta-hydroxy-beta-methylbutyrate, ascorbic acid, dl-alpha-tocopheryl acetate, aspartame, zinc sulfate, acesulfame potassium, and vitamin B12.	Level 1 Level 3 Level 5	Ingestible Juven contains a unique blend of key ingredients to help support wound healing	Support wound healing by enhancing collagen production in as little as 2 weeks and to help build and maintain LBM in 4 weeks; also intended as a treatment for sarcopenia patients	MoA was not directly stated in peer-reviewed literature. Company claims collagen proteins give structural support to cells, but they also modulate inflammatory cell function; arginine promotes blood flow and protein production, which can contribute to wound healing; glutamine supports new tissue development and the immune system; vitamins C, E, B12, and zinc support the wound healing process; arginine and HMB improve metabolism and reduce inflammatory response	The specialized amino acid supplement led to a significant increase in collagen deposition (as reflected by hydroxyproline content) in subcutaneously implanted polytetrafluoroethylene tubes; oral consumption reduced cesarean scarring and promoted wound healing; no significant improvement in healing DFU	^223–230

Collagen-based products levels of evidence. Level 1 ≥ 3 RCT; Level 2 = 1 well-designed RCT/multi-site study; Level 3 = clinical studies—observational/mechanism of action (MoA); Level 4 = historical cohort (retrospective) or case-control studies (retrospective with control group); Level 5 = other clinical studies (case series or studies as reference treatment, human ex vivo MoA); Level 6a = large animal with MoA; Level 6b = large animal observational; Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Table 2.

Level of evidence 2

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action	Outcomes study/Trial	References
ArteGraft ■ LeMaitre Vascular	Acellular collagen vascular graft of bovine origin	Level 2 Level 3 Level 4 Level 5 Level 6a	Long-term durability and secondary patency rates; easy surgical handling and suturability; strong collagen matrix that retains the original artery cross weave	Intended for use distal to the aorta as a segmental arterial replacement, as an arterial bypass, as an arteriovenous shunt where more conventional methods have proven inadequate, or as an arterial patch graft	ArteGraft is simply to serve as a substitute conduit for blood where bypass or replacement of occluded/diseased arterial segments is required, or to establish a conduit for hemodialysis	Conformity to the applicable requirements and confirmed that the subject device is safe and performs as intended and claimed; is a state-of-the-art device for use for vascular access or in vascular bypass or repair; limb salvage rate at one year was 83.6% and at five years was 86.2% for patients with critical limb ischemia	^231–236
Collagen meniscus implant (CMI) ■ Stryker	99% tendon-derived type I bovine collagen; small quantities of GAGs: chondroitin sulfate, sodium hyaluronate	Level 2 Level 5 Level 7b	CMI implant reinforces soft tissue and provides a resorbable scaffold that is replaced by the patient’s own soft tissue; is not a prosthetic device and is not intended to replace normal body structure	Designed to function as an absorbable template to facilitate host meniscus tissue regeneration in patients who have an irreparable meniscus tear or loss of meniscus tissue, ACL reconstruction, knee realignment, chondral resurfacing	The CMI meniscus tissue implant is slowly absorbed and replaced by patient’s native collagen tissue; can be preseeded with mesenchymal stem cells (MSCs) or meniscus cells before implantation	One year after implantation, hybrid fibrous and meniscus-like fibrochondrocytic matrix have been identified within the collagen implant suggesting its potential to integrate with host tissue; at that time, remnants of the CMI may be present in 10% to 25% of cases; improves short-term outcomes, but tissue deposition is limited and (partial) resorption occurs in several years	^237–240
ColActive Plus an Colactive Plus AG Hartmann USA	Collagen, sodium alginate, EDTA carboxymethyl cellulose, silver chloride	Level 2 Level 5 Level 7b	Dressing maintains a moist wound environment at the wound surface that aids in the formation of granulation tissue and epithelialization; silver chloride provides an effective broad spectrum of antimicrobial activity; helps remove zinc to inhibit matrixins	Management of full- and partial-thickness wounds including: pressure injuries, diabetic ulcers, ulcers caused by mixed vascular etiologies, venous ulcers, donor and graft sites, abrasions, traumatic wounds healing by secondary intention, dehisced surgical wounds, first-, and second-degree burns	Gelatin sheet that directly contacts with wound and exudates; the dressing maintains a moist wound environment at the wound surface that aids in the formation of granulation tissue and epithelialization; EDTA inhibits MMPs; carboxymethyl cellulose and alginate maintain moist wound environment and activate silver ion; antimicrobial silver chloride disrupts bacterial metabolic cycle	The use of Colactive silver dressing has less pain, less itching in the donor area, and a shorter average recovery time than Vaseline gauze	^{221,241–245}
CollaCote ■ Zimmer Biomet	Porous, nonfriable collagen sponge; type1 bovine collagen	Level 2 Level 5 Level 7a level 7b	Aids in wound closure and controls bleeding in palatal donor sites, mucosal flaps; provides matrix for tissue ingrowth	Intended for surgical wounds, periodontal surgical wounds, extraction sites, dental sores, oral ulcers (noninfected or viral), suture sites, burns, traumatic wounds; being used to treat bone defects associated with endodontic treatment complications	Host cell migration from surrounding tissue, osteoinductivity, mediated by collagen structure and homogeneously distributed micropores; absorbs and regulates bleeding and blood clots while also protecting the wound site and promoting healing	CollaCote significantly accelerated palatal wound healing and reduce the patient’s pain and discomfort	^{246–251,252}
CollaGraft ■ Zimmer Biomet	Porous beads; 60% hydroxyapatite and 40% tricalcium phosphate ceramic, fibrillar type I bovine collagen	Level 2 Level 4 Level 6b Level 7a	Bridges segmental long bone defects	Treatment of acute long bone fractures and traumatic osseous defects with bone marrow and rigid fixation; can impregnated with antibiotics	Hydroxyapatite provides a slightly resorbable scaffold to facilitate new bone ingrowth and calcification; tricalcium phosphate is a resorbable component that binds bone material; these components together provide a biodegradable osteoconductive scaffold that promotes new bone ingrowth and remodeling while preserving mechanical strength; can be used with autogenous bone marrow for treating long fractures	Showed the same efficacy as autogenous iliac graft in the treatment of acute long bone fractures over 6–12 months; CollaGraft with bone marrow: at 21 days, new woven bone and osteoblasts were seen in contact with both the collagen and hydroxyapatite/β-tricalcium phosphate components; newly formed bone ossicles were observed in association with the collagen component	^253–259
CosmoDerm □ Abbvie	Human-based collagen	Level 2 Level 4 Level 5	Replenish skin’s lost collagen	Injected into the superficial papillary dermis for correction of soft tissue contour deficiencies, such as wrinkles and acne scars	MoA was not directly stated in peer-reviewed literature. Company claims it is an injectable dermal filler formulated for fine line wrinkles and facial contour defects.	Resulting nonsevere adverse event rate of 33.3% for CosmoDerm (1/3 injections)	^260–262
CosmoPlast □ Abbvie	Human-based collagen crosslinked with glutaraldehyde	Level 2 Level 5 Level 6b	Improves facial appearance by smoothing wrinkles and folds	Injected into the mid to deep dermis for correction of soft tissue contour deficiencies, such as wrinkles and acne scars.	MoA was not directly stated in peer-reviewed literature. Company claims it is an injectable dermal filler formulated for fine line wrinkles and facial contour defects.	Treatment of mid to deep dermal defects lasts for 4–7 months)	^263–267
DermACell ■ LifeNet Health	Acellular human-derived dermal matrix that is decellularized, removing donor DNA, and retains native growth factors, collagen, and elastin	Level 2 Level 4 Level 5 Level 7a	Matracell removes a minimum of 97% of donor DNA, allowing for rapid cellular infiltration and re-vascularization in wound healing	Treatment of chronic nonhealing wounds such as diabetic foot ulcers	Matracell removal of donor DNA allows for rapid cellular infiltration and revascularization; CD31 positive cell infiltration and vessel formation by day 7; high levels of fibroblast and blood vessel infiltration suggest DermACELL tissue incorporates into the host tissue	Significantly higher percentage of completely healed ulcers by the 16-week follow-up compared to the conventional care group	^{98–100,268–271}
Dermagraft ■ Organogenesis	Three-dimensional polymer scaffold containing metabolically active human fibroblasts that secrete collagen, other ECM proteins, growth factors, and cytokines	Level 2 Level 3 Level 7a Level 7b	Diabetic foot ulcer treatment composed of fibroblasts, extracellular matrix, and a bioabsorbable scaffold.	Treatment of full-thickness diabetic foot ulcers greater than six weeks duration which extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure. Indications beyond DFUs, include the treatment of dystrophic epidermolysis bullosa, chronic surgical wounds, and wound dehiscence after amputations.	During manufacturing, human fibroblasts proliferate to fill the interstices of this polyglactin mesh scaffold and secrete collagen, other ECM proteins, growth factors, and cytokines; remains metabolically active following wound bed implantation	At 12 weeks after initiation of therapy, Dermagraft treatment led to a 64% increase in the proportion of patients exhibiting complete wound closure when compared with patients receiving conventional therapy	^272–278
Evolence ■ Johnson and Johnson	Collagen filler; 3.5% type 1 fibrillar porcine collagen crosslinked with d-ribose	Level 2 Level 5 Level 7a	Reduces wrinkles and facial folds; less immunogenic than bovine collagen	Injectable product indicated for the correction of moderate to deep facial wrinkles and folds such as nasolabial folds	Glymatrix crosslinking technology improves clinical persistence by providing resistance to collagenolytic degradation; fibroblast infiltrates colonize the matrix and secrete new collagen; areas of new collagen deposition become vascularized and, after 12–24 months, become integrated in the dermis	6 months post-OCR visit, 91.2% of subjects continued to rate the nasolabial fold treated with Evolence as “better” or “much better” than pretreatment; no hypersensitivity reported; maintained durability for 18 months on average	^279–282
Fibracol Plus □ Johnson & Johnson	Collagen wound dressing with alginate; 90% collagen, 10% calcium alginate	Level 2 Level 5 Level 7a Level 7b	Structural support of collagen with the exudate management of alginate; absorbent alginate composition helps maintain a moist wound environment conducive to granulation tissue formation and epithelialization	Management of exuding wounds including: full- and partial-thickness wounds; pressure injuries; venous ulcers; ulcers caused by mixed vascular etiologies; diabetic ulcers; donor sites and other bleeding surface wounds; traumatic wounds healing by secondary intention; dehisced surgical incisions; pack into deep wounds	Alginate supports a moist wound environment; collagen component promotes cellular and vascular in-growth, as well as fibroblast proliferation, resulting in granulation tissue and neoepithelialization at the wound site	75 foot ulcer patients; 81% wound area reduction (61% control group); complete wound healing outcomes in 48% patients (compared with 36% in the control group)	^{220,283–286}
Gintuit ■ Organogenesis Inc.	Allogeneic cultured keratinocytes and fibroblasts in bovine collagen	Level 2 Level 3	Secretes human growth factors and cytokines and contains extracellular matrix proteins; these factors are known to be involved in wound repair and regeneration.	Indicated for topical (nonsubmerged) application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults	MoA was not directly stated in peer-reviewed literature. Company claims that Gintuit grafting over vascular wound beds creates color and texture matched tissue for treating mucogingival conditions, without providing root coverage	Evaluated in two clinical studies in adults with insufficient gingival tissue; in each of the two studies, Gintuit was associated with an increase of at least 2 mm of gingival tissue in at least 50% of the study subjects	^287–289
Grafix □ Smith & Nephew	Human placental membrane allograft; ECM (collagen, elastin, laminin, fibronectin), mesenchymal stem cells, and growth factors	Level 2 Level 4 Level 5	Includes MSCs in the collagen-rich ECM to enhance and improve wound healing in the clinical setting	Wound cover that can be used for the treatment of both acute and chronic wounds, including but not limited to DFUs, VLUs, pressure ulcers, burns, surgical incisions and dehiscence, pyoderma gangrenosum, and epidermolysis bullosa	MoA was not directly stated in peer-reviewed literature. Company claims National Institute for Health and Care Excellence found Grafix to have the highest overall effect with “no serious risk of bias.” Cryopreservation resulted in 80% cell viability within membrane post-thaw; cells and growth factors are integral components of the membrane ECM, where MSCs were presumed to have most beneficial effects in wound healing in elderly patients.	Complete wound closure at 12 weeks in 62% of the patients with chronic DFU	^290–295
GraftJacket ■ Stryker	Cadaveric skin collagen-based allograft; allogeneic cultured keratinocytes and fibroblasts in bovine collagen; elastin, collagen, hyaluronan, fibronectin, blood vessel channels	Level 2 Level 3 Level 5 Level 6b	GraftJacket can be used to provide supplemental support, protection, and reinforcement of tendon and ligamentous tissues, or other homologous use	Repair or replacement of damaged or inadequate integumental tissue, such as diabetic foot ulcers, venous leg ulcers, pressure ulcers, or for other homologous uses of human integument; rotator cuff injuries; Achilles tendon repair	Acellular scaffold promotes new cellular in-growth that developed a remodeled tendon-like structure 6 months postsurgery; acellularity makes graft less immunogenic; intact collagen ECM strengthens graft; intact blood vessel channels support revascularization and cellular infiltration to promote graft healing	Acellular human dermal matrix augmentation of large (>3 cm) cuff tears involving 2 tendons showed better ASES and Constant scores and more frequent intact cuffs as determined by gadolinium-enhanced magnetic resonance imaging (MRI); intact repairs were found in 85% of the augmented group and 40% of the nonaugmented group; no adverse events related to the acellular human dermal matrix were observed	^296–299
NeuraGen Nerve Guide □ Integra LifeSciences	Nerve conduit; bovine type 1 collagen tube	Level 2 Level 4 Level 5 Level 7a Level 7b	Biocompatible ultra-pure collagen that allows for controlled resorption; the conduit’s precisely engineered porosity supports natural nerve regeneration by allowing nerve growth factors and Schwann cells to infiltrate	Indicated for the repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.	Provides a protective environment across nerve discontinuities, as well as an isolated conduit environment guiding axonal regrowth; has been used safely as a nerve graft seeded with MSCs to further promote motor nerve regeneration	Recovery of sensory and motor functions using collagen conduits was equivalent to direct suture at 24 months after repair when nerve gap inside tube was 6 mm or less; NeuraGen conduit repair also resulted in 40% less time in or than direct suture-repair	^300–304
NuShield Organogenesis Inc.	Dehydrated human placental allograft with growth factors, ECM proteins (collagen type I, III, and high levels of IV, V, and VI), elastin, glycoproteins, proteoglycans including hyaluronic acid, dermatan sulfate, and chondroitin sulfate	Level 2 Level 5 Level 7b	Acts as an adjunct to soft tissue healing with excellent regenerative, anti-inflammatory, and angiogenic properties	Direct application in wrapping or suturing around tendons; on-lay graft to protect tendons, nerves, spine adhesions and fibrosis, acute and chronic wounds	Cytokines and growth factors (EGF, PDGF, transforming growth factor-β [TGF-β], bFGF) released from graft are chemotactic for keratinocytes and fibroblasts, promoting migration and proliferation; paracrine signaling following exposure to NuShield results in expression changes in keratinocytes and fibroblasts for genes that are mitogenic, regulate inflammation, or regulate proliferation	48% greater probability of wound closure in favor of the dACM (NuShield) group	^305–309
Permacol □ Medtronic	Crosslinked porcine dermal collagen surgical mesh	Level 2 Level 3 Level 4 Level 5 Level 7a	Combining the tensile strength of synthetic hernia repair materials with the biocompatibility of an acellular porcine dermal implant; surgical implant delivers proven durability and strength for ventral hernia repair and abdominal wall reconstruction	Support and reinforce soft tissue in surgical procedures including rectal intussusception, congenital diaphragmatic hernia, and abdominal wall hernia repair	Crosslinking is introduced into the structure, making it resistant to the collagenase enzymes responsible for the breakdown and resorption of implanted collagen; crosslinking also protects against bacterial degradation; postimplantation there is an acute inflammatory response that facilitates infiltration and healing; angiogenesis produces capillary ingrowth; implant gradually becomes permanently incorporated into the tissue with well-organized collagen and skeletal muscle	Permacol mesh in BioLIFT is feasible and achieves a high primary healing rate of 80%; trend of lower recurrence rates than competitors	^310–319
PriMatrix and PriMatrix Ag Dermal Repair Scaffold □ Integra LifeSciences	Acellular fetal bovine dermis sheet; type III collagen; PriMatrix Ag contains silver	Level 2 Level 3 Level 4 Level 5 Level 7b	Provides an environment that supports cellular repopulation and revascularization; the silver in PriMatrix Ag is intended to prevent microbial colonization of the device	Indicated for management of wounds including: partial and full thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, second-degree burns, surgical wounds, trauma wounds, tunneled/undermined wounds, and draining wounds; not indicated for third degree burns	Has biocompatibility as well as the ability to trap and bind the patient’s own cells and growth factors within the porous matrix at the time of surgery; implants trigger an initial inflammatory cell infiltrate followed by migration of mesenchymal cells and neovascularization; progressive remodeling by host cell infiltrates replaces graft tissue with histologically normal-appearing host tissue	In a prospective multicenter study, 76% of patients treated with PriMatrix for management of diabetic foot ulcers achieved closure by 12 weeks; a retrospective case series of 43 consecutive partial- or full-thickness wounds treated with either PriMatrix or PriMatrix with negative pressure wound therapy showed that 88.3% of cases achieved wound closure through re-epithelialization of the dermal scaffold	^320–329
Promogran Prisma □ Johnson & Johnson	55% collagen, 44% ORC, 1% silver with 25% w/w ionically bound silver (Promogran ORC +Ag)	Level 2 Level 4 Level 5 Level 7b	In the presence of exudate, matrix transforms into a soft, confirmable, biodegradable gel, and thus allows contact with all areas of the wound; the dressing helps create a moist wound bed and an environment that supports wound healing; addition of silver provides antibiosis to chronic wounds	Indicated for the management of exuding wounds including: pressure injuries, diabetic ulcers, venous ulcers, ulcers caused by mixed vascular etiologies, partial- and full-thickness wounds, donor sites and other bleeding surface wounds, abrasions, traumatic wounds healing by secondary intention, and dehisced surgical wounds	Reduces MMPs and free radicals in wounds; removes excess metal ions; protects growth factors and proteins that promote wound healing and tissue formation	Randomized controlled trial demonstrated that collagen/ORC/silver treatment significantly increased healing compared with the control treatment, using healing criteria of 50% reduction in wound area by week 4	^330–334

Collagen-based products levels of evidence. Level 2 = 1 well-designed RCT/multi-site study; Level 3 = clinical studies—observational/mechanism of action (MoA); Level 4 = historical cohort (retrospective) or case-control studies (retrospective with control group); Level 5 = other clinical studies (case series or studies as reference treatment, human ex vivo MoA); Level 6a = large animal with MoA; Level 6b = large animal observational; Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Table 3.

Level of evidence 3

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action	Outcomes study/Trial	References
ACell MatriStem Matrix □ Integra LifeSciences	Acellularized basement membrane and tunica propria layers of the porcine bladder; ECM proteins that include type I/III collagen, glycosaminoglycans, growth factors	Level 3 Level 4 Level 6a	Wound management solution for irregular, tunneled, or undermined wounds; applied as either a powder or paste; the particulate solution provides intimate contact with all areas of the wound bed	Treat esophagojejunal anastomotic leaks; vesicovaginal fistula; deep partial thickness burns and wounds; esophageal stenosis; seal surgical sites and prevent leakage.	Induces a host-derived tissue remodeling response; stimulates neovascularization through a number of growth factors and functional proteins such as collagen, laminin, and elastin; inflammatory reactions are uncommon, given the acellular, inert nature of urinary bladder matrix	Use in deep partial-thickness burns enabled healing by 29 days on average without requiring autografts; 75% of cases of vesicovaginal fistula treated with MatriStem had no fistula drainage and progressed to full healing; an alternative for the treatment of esophageal stenosis is presented, which uses a biological scaffold and an innovative surgical procedure where all patients had a favorable clinical outcome with immediate recovery from the procedure and reinstated oral intake after 7 days	^335–340
CollaPlug ■ Zimmer Biomet	Type I/III bovine collagen absorbable non-friable sponge	Level 3 Level 5 Level 7b	Material to help promote clotting	Control bleeding and stabilize blood clots as well as protect the wound bed while accelerating the healing process.	MoA was not directly stated in peer-reviewed literature. Company claims that CollaPlug enhances clot formation and accelerates formation of granulation tissue while it absorbs up to 60 times dressing weight in fluids.	Effective local hemostatic material following minor oral surgery in patients under oral anticoagulant therapy; also shows acceleration of soft tissue healing and reduce postoperative pain	^341–345
CopiOs Bone Void Filler □ ZimVie	Calcium phosphate, dibasic (DICAL) and purified type 1 bovine collagen	Level 3 Level 6b Level 7a Level 7b	Synthetic bone graft material consisting of mineralized, lyophilized collagen that has been formed into sponges of various sizes for surgical implantation.	Used for bone grafting and rigid fixation techniques for stabilizing bone voids	During the remodeling process CopiOs Bone Void Filler act as a scaffold that provides a moderately acidic environment that promotes solubility of osteoinductive growth factors for new bone formation. CopiOs promotes aerobic glycolysis and proliferation in cells seeded within its collagen matrix. Seeded cells have fast calcium release and high levels of p38 and ERK phosphorylation, suggesting that CopiOs promotes activation of these pathways.	Patients undergoing spinal fusion with CopiOs bone void filler was used showed a decrease in the volume of bony void at 3- and 6-month follow ups, with no pain reported.	^346–349
Cutimed Epiona □ Essity	90% native bovine collagen, 10% calcium-sodium alginate	Level 3 Level 4 Level 5	Mimics the function of a healthy dermis and boosts the wound healing process; eliminates harmful factors by binding MMPs; enhanced granulation by promoting cell growth	Easy to combine with your current therapies (e.g., compression therapy); broad indication for treatment of all wounds healing by secondary intention, free of necrotic tissue; can be folded or rolled up depending on wound type (deep wounds); indicated for diabetic foot ulcers, donor sites, pressure injuries, surgical wounds, trauma wounds, venous leg ulcers	MoA was not directly stated in peer-reviewed literature. Company claims that contact with wound exudate rehydrates Cutimed Epiona to a gelatinous form that keeps wound environment moist; binds and inhibits MMPs and reduces inflammation	Patients exhibited a decrease and wound exudate and wound area after 3 weeks of treatment with no infection or adverse events reported	^350–353
INSPIRIS RESILIA ■ Edwards Lifesciences	Aortic valve, treated bovine pericardium	Level 3 Level 4 Level 5	Improves heart valve replacement safety and efficacy; significant improvement in calcium-blocking properties	Indicated for aortic valve replacement	MoA was not directly stated in peer-reviewed literature. Company claims that stable-capping permanently blocks free aldehydes to prevent calcium binding within the tissue	Patients showed a reduction of transvalvular pressure gradients and lower trans-prosthetic pressure gradients	^354–358
Integra Bilayer Matrix Wound Dressing (IBWMD) □ Integra LifeSciences	Bovine type I collagen/chondroitin-6-sulfate sponge with thin silicone layer on the epidermal surface	Level 3 Level 4 Level 5	Controlled pore size, porosity and degradation rate of the sponge enables cells to infiltrate, proliferate, and aid in the healing process; the semi-permeable silicone layer provides epidermal-like protection and moisture control	Support the management of wounds including: partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, surgical wounds, trauma wounds, and draining wounds; not indicated for third degree burns	Facilitates neodermal reconstruction with regenerative rather than inflammatory healing; fibroblasts infiltrate by day 7, myofibroblasts infiltrate by week 3 and deposit collagen, by week 4 native collagen replaces Integra collagen and becomes fully vascularized; following vascularization, silicone cover is removed; can provide antibiotic delivery	IBWM demonstrated progressive DFU wound healing, with 95% mean wound reduction at 12 week; complete wound closure was achieved by 70% of patients after 12 weeks; no recurrences were observed at follow-up	^359–364
Integra Wound Matrix □ Integra LifeSciences	Bovine type I collagen/chondroitin-6-sulfate sponge	Level 3 Level 4	Controlled pore size, porosity, and degradation rate enables cells to infiltrate, proliferate, and aid in the healing process	Support the management of wounds including: partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds; not indicated for third degree burns	MoA was not directly stated in peer-reviewed literature. Company claims IWM is an effective method to treat deep skin defects in elderly multimorbid patients with deep facial wounds by promoting dermal regeneration	IWM resulted in favorable take rates, functional and early cosmetic outcomes in deep facial wounds; all but one graft had complete take without any complication, whereas one graft had partial graft loss (30%); all defects showed significant shrinkage of 61%	^365–369
KollaGen II Simple Supplements	Avian sternal collagen type II hydrolysate	Level 3	Nutritional supplement to reduce symptoms of joint damage	A dietary supplement that may be beneficial for patients suffering from degenerative joint diseases, including cartilage injuries, connective tissue disorders, polychondritis, joint defects, osteoarthritis, and rheumatoid arthritis	Some orally administered collagen type II hydrolysate-derived peptides are absorbed by the intestine and are circulated in the blood stream to eventually reach cartilage tissue and, possibly, activate collagen biosynthesis in chondrocytes to alleviate joint pain	Administration of 2,000 mg/day of collagen type II hydrolysate for 60 days improved essential symptoms in individuals suffering from joint diseases, including the range of motion, general pain, and muscle strength	³⁷⁰
SkinTemp II □ Human BioSciences	Collagen sheets; 100% nonhydrolyzed type 1 bovine native collagen	Level 3 Level 5 Level 7b	Kollagen technology process protects and retains significantly more native triple helical protein structure, thus allowing superior stability of the molecule and scaffolding through all four phases of wound healing	Management of burns, scrapes, blisters, sores, ulcers, acute and chronic wounds, superficial, partial- and full-thickness wounds, infected and noninfected wounds, and minimal to heavily exudating wounds	Triple helical structure is more stable, having high tensile modulus in wound environment, providing scaffold to chemotactically attract and guide fibroblast migration for collagen deposition and improved wound healing	Type I bovine collagen matrix provided a safe, readily available alternative to traditional methods of second intention healing; it minimized wound care while reducing the time for complete healing	^371–374

Collagen-based products levels of evidence. Level 3 = clinical studies—observational/mechanism of action (MoA); Level 4 = historical cohort (retrospective) or case-control studies (retrospective with control group); Level 5 = other clinical studies (case series or studies as reference treatment, human ex vivo MoA); Level 6a = large animal with MoA; Level 6b = large animal observational; Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Table 4.

Level of evidence 4

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action	Outcomes study/Trial	References
BriDGE □ Harbor MedTech	Stabilized acellular equine pericardial collagen matrix (sPCM) wound care dressing	Level 4 Level 5 Level 6a Level 7a	Proteolytic enzyme degradation resistant, fully flexible cross-linked tissue that may be used as wound care dressing; a safe and beneficial treatment for neuropathic wounds; accelerates wound healing and reduces biofilm formation	Neuropathic foot wounds, difficult-to-treat and recalcitrant wounds of the lower extremity including diabetic, venous, trauma, vasculitic, and postsurgical wounds	Primary transient inflammatory response followed by wound healing; antimicrobial and antibiofilm properties; enhanced epithelialization and collagen deposition and maturation that promote wound healing	Closed wounds twice as fast as the published results of other skin substitute products; did not require weekly re-application	^44,375–377
Cytal Wound Matrix/MicroMatrix UBM Particulate □ Integra LifeSciences	Porcine urinary bladder matrix (UBM) sheet/porcine UBM particulate	Level 4 Level 5	Enables a shift from an inflammatory wound environment into one that facilitates cellular infiltration and fast formation of site-appropriate, vascularized tissue	Cytal Wound Matrix: indicated for the management of wounds including: partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds; not indicated for third-degree burns. MicroMatrix UBM Particulate: indicated for the management of wounds including: partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds	MoA was not directly stated in peer-reviewed literature. Company claims that Cytal Wound Matrix: Supports a shift from an inflammatory wound environment into one that facilitates cellular infiltration and fast formation of site-appropriate, vascularized tissue MicroMatrix UBM Particulate: Supports a shift from an inflammatory wound environment to one that facilitates rapid revascularization to support wound closure	A prospective case control study assessed wound management with UBM which showed a statistically significant decrease in M1 to M2 scores for both diabetic and nondiabetic patients, which correlated with the rate of wound area reduction; a case series that addresses the utilization of UBM products (both Cytal and MicroMatrix) in a surgical care algorithm for combat injuries in 51 cases; in 86% of cases, there was successful granulation tissue formation or preparation of the wound bed for secondary DRT placement, skin grafting, or flap coverage	^378–381
Healos □ DePuy Synthes	Bone graft substitute; mineralized collagen bone matrix; type 1 bovine collagen and hydroxyapatite particles (strips/pads)	Level 4 Level 7a Level 7b	Provides a bone void filler that is resorbed and remodeled into bone as part of the natural healing process	For use in filling bony voids or gaps that are not intrinsic to the stability of the bony structure; substitute for autologous iliac crest bone graft when used in fusion procedures of the lumbar spine	Healos loaded with connective tissue growth factor (CTGF) and mesenchymal progenitor cells produce progeny cells that differentiate into osteoblasts and osteocytes, which can bridge the bone defect and retained a large marrow compartment	21 patients were included and all patients achieved successful fusion; computed tomography scans showed solid bilateral fusion with bridging bone (Grade I) in all patients, but solid unilateral fusion with bridging bone (Grade II) was detected for one patient at one level	^382–385
SurgiMend Collagen Matrix □ Integra LifeSciences	Acellular fetal bovine dermis sheet	Level 4	Implantation to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes	Indicated for plastic and reconstructive surgery, muscle flap reinforcement, hernia repair including abdominal, inguinal, femoral, diaphragmatic, scrotal, umbilical, and incisional	MoA was not directly stated in peer-reviewed literature. Company claims that SurgiMend supports rapid revascularization and integrates with host tissue for a durable, mechanically robust repair	A retrospective case series of a single surgeon’s experience with abdominal wall reconstruction with reinforcement using Surgimend showed no recurrence in 93% of patients at 18 months, which was significantly better than the authors previous outcomes in a prior series where Surgimend was not used	^386–388

Collagen-based products levels of evidence. Level 4 = historical cohort (retrospective) or case-control studies (retrospective with control group); Level 5 = other clinical studies (case series or studies as reference treatment, human ex vivo MoA); Level 6a = large animal with MoA; Level 6b = large animal observational; Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Table 5.

Level of evidence 5

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action	Outcomes study/Trial	References
Biostep and Biostep AG □ Smith & Nephew	Semi-denatured cross-linked porcine collagen, EDTA, alginate, silver, carboxylmethylcellulose (CMC)	Level 5	Collagen binds excess MMPs while EDTA irreversibly deactivates MMPs; alginate component to absorb a high level of moisture; antibacterial activity of silver to help maintain bacterial balance for contaminated and colonized wounds	Management of full-thickness and partial-thickness acute and chronic wounds including: pressure injuries, diabetic ulcers, ulcers caused by mixed vascular etiologies, venous ulcers, first-, and second-degree burns, donor/graft sites, abrasions, dehisced surgical wounds, and traumatic wounds healing by secondary intention	Crosslinked collagen attracts MMPs so the dressing, and not native collagen, is degraded; EDTA binds zinc to deactivate MMPs; antimicrobial activity of silver ions to inhibit microbial ingress of the dressing and maintain bacterial balance; maximum surface area of collagen dressing, CMC, and physiological pH allows maximum exudate absorption and promotes wound healing	Enhanced granulation, tissue regeneration, and epithelialization were achieved within a relatively short time period (1–2 weeks); a patient presented with a lateral malleolus ulcer secondary to minor trauma that had failed to respond to 4 weeks of conventional wound care. Biostep dressing was applied, and the wound had nearly closed by 21 days of treatment.	^389–391
CollaTape ■ Zimmer Biomet	Type 1 bovine tendon-derived collagen	Level 5 Level 7b	Control bleeding and stabilize blood clots as well as protect the wound bed while accelerating the healing process; porous, absorbable matrix supports delicate new tissue	Intended for localized ridge defects, socket grafting, oral ulcers (noninfected or viral), periodontal surgical wounds, burns	Rough surface, hydrophilicity, and sponge-like structure of collagen promotes osteoblast adhesion, mediated by osteoblast surface fibronectin; newly remodeled bone mass has been mainly attributed to type I collagen-driven angiogenesis; long term ridge preservation following tooth extraction is limited due to Collatape degradation within 5 weeks	Membrane permitted palatal fibroblast and epithelial cell adhesion, proliferation, and distribution which led to formation of mucosa-like tissue	^{248,392–395}
Endoform □ Aroa Biosurgery, Ltd.	Natural dermal template; 90% intact native collagen, 10% ECM components: ovine forestomach, collagen type I, III, IV, elastin, GAGs, proteoglycans, FGF, laminin, fibronectin	Level 5 Level 7b	Rehydrated with exudate or sterile saline, the dermal template transforms into a soft conforming sheet, which is naturally incorporated into the wound over time; retains the native extracellular matrix-associated macromolecules, including fibronectin, glycosaminoglycans, laminin, and elastin; broad-spectrum MMP reduction	Intended for Hidradenitis suppurativa-chronic inflammatory skin disease, pressure ulcers, diabetic foot ulcers, surgical wounds, tunneling, and traumatic wounds	Provides a natural porous bioscaffold for rapid cell infiltration while reducing excess MMP; contains >150 ECM proteins and residual vascular channels to support the establishment of new vasculature	Wound dimensions decreased in 21 of 24 wounds, including patients with multiple comorbidities	^396–398
FACIALGAIN Sunmax Biotechnology	Crosslinked porcine collagen implant with lidocane	Level 5 Level 6b	Crosslinked porcine collagen dermal filler injections can serve as a minimally invasive approach to enhance skin laxity	Dermal filler injections for treating dermatochalasis and periorbital hyperpigmentation; collagen implants for dermal contour correction.	MoA was not directly stated in peer-reviewed literature. Company claims glutaraldehyde cross-linking of collagen fibers increases the product stability and mechanical properties, while lidocaine is added to mitigate pain	Tissue in-growth was observed in the RPC constructs along with neovascularization and granulation tissue; at the 6-month time point, the RPC implant material blended somewhat imperceptibly with native, pre-existent collagen and accurate reaction zone measurements of the implant and associated host tissue response could not be made	^399–402
Gentrix Surgical Matrix □ Integra LifeSciences	Porcine UBM sheet	Level 5 Level 6a Level 6b	Provides mechanical reinforcement; facilitates the body’s ability to remodel site-appropriate tissue	Implantation to reinforce soft tissue where weakness exists in patients requiring gastroenterological or plastic, reconstructive and urological surgery; some Gentrix devices are indicated to minimize tissue attachment to the device in case of direct contact with viscera	MoA was not directly stated in peer-reviewed literature. Company claims that Gentrix devices maintain an intact epithelial basement membrane and facilitates the body’s ability to remodel site-appropriate tissue	Retrospective case series of 64 patients who underwent complex ventral incisional hernia repairs (55% retrorectus and 44% intraperitoneal) reinforced with UBM; at the 36-month follow-up, there was a 15.6% recurrence rate and no cases of erosion, fistula formation, or need for mesh explantation; three patients had a full-thickness fascial biopsy which showed functional remodeling of site-appropriate connective tissue	^403–408
Ossix Plus □ Dentsply Sirona	Porcine-derived type 1 collagen-based sugar cross-linked membrane	Level 5 Level 6a Level 7a Level 7b	Provides true barrier effect for 4–6 months, ossifies and contributes to improved long-term outcomes	Intended for use during the process of guided bone regeneration (GBR) and guided tissue regeneration (GTR) as a biodegradable barrier for: ridge augmentation for later implant insertions; simultaneous ridge augmentation and implant insertions; ridge augmentation around implants inserted in extraction sites; alveolar ridge preservation consequent to tooth extractions; over the window in lateral window sinus elevation procedure; implants with vertical bone loss due to infection, only in cases where satisfactory debridement and implant surface disinfection can be achieved; intra bony defects around teeth; treatment of recession defects, together with coronally positioned flap; in furcation defects in multi-rooted teeth	Promotes mineralized tissue formation around the site of implants; high cellular barrier function of cross-linked collagen and pepsin treatment (prevents host cell infiltration and reduces inflammation; membrane is still permissible for nutrient permeation	Membrane-protected site had formation of well-mineralized tissue at 12 weeks following exodontia, with minimal changes in alveolar ridge dimensions and no signs of membrane ossification	^409–413
PSDV □ Baxter International Inc.	Peri-strip dry staple (PSD) line reinforcement with Veritas collagen matrix; dehydrated bovine pericardium vascular patch	Level 5	Increase the strength of staple-lines and/or reduce the risk of bleeding	Prosthesis for the surgical repair of soft tissue deficiencies using surgical staplers when staple line reinforcement is needed, including laparoscopic gastric bypass	Differs from traditional PSDs in that it is not crosslinked with glutaraldehyde; acellular collagen matrix promotes host fibroblast infiltration and capillary ingrowth; remodeling of this nonpermanent staple line buttress renders it indistinguishable from host tissues	The median duration of air leaks and median drainage time was significantly shorter in the PSDV group	^151,414,415
Puracol □ Medline	Collagen wound dressing; 100% type 1 collagen with a high degree of nativity	Level 5 Level 7b	Jump-starts the wound healing process, making it ideal for wounds that are chronic or stalled; high gel integrity	Ideal for pressure, venous, diabetic ulcers, partial- and full-thickness wounds, ulcers caused by mixed vascular etiologies, burns, donor sites, and other surface wounds, scalp reconstruction, abrasions, traumatic wounds healing by secondary intention and dehisced surgical wounds	MoA was not directly stated in peer-reviewed literature. Company claims that Puracol retains triple-helix structural stability that persists in contact with liquid and aids in wound bed preparation for subsequent skin substitute; fragile collagen laminas within Puracol are reduced to thin collagen fibrils cross-linking wider collagen bundles of fibers, possibly making them inaccessible to collagenase; interaction with lymphocytes showed no appreciable difference in collagen matrix, contributing to matrix resilience during host cell infiltration; porosity of 80% promotes host cell infiltration and adhesion, which aids in wound healing	Can be tethered to antimicrobial peptides (AMP); collagen-tethering of AMPs without the harmful side effects of current approaches (e.g., bacterial resistance, general toxicity, scarring) and utilizing their wound healing functionality have important implications for the future of tethered AMPs	^221,416,417
Puracol Plus and Puracol Plus Ag □ Medline	Collagen dressing with microscaffold; 100% type I native bovine collagen; Puracol Plus Ag+ contains hydrated silver chloride	Level 5 Level 7b	Helps jump-start stalled or chronic wounds when antimicrobial properties of silver are desired and help promote natural healing; Puracol Plus Ag+ silver adds antimicrobial properties	Indicated for pressure, venous, diabetic ulcers, partial- and full-thickness wounds, ulcers caused by mixed vascular etiologies, first- and second-degree burns, donor sites and other surface wounds, abrasions, traumatic wounds healing by secondary intention, and dehisced surgical wounds; solution for tunneling wounds that are difficult to dress because of the tendency of nonbiodegradable dressing materials to be retained in the wound even after their attempted removal	MoA was not directly stated in peer-reviewed literature. Company claims that Puracol Plus retains triple-helix structural stability that persists in contact with liquid and aids in wound bed preparation for subsequent skin substitute; triple helix collagen structure binds MMPs, resolving inflammation and supporting proliferation; hydrated silver chloride provides antibacterial properties	Increased rates of healing were found in the xenograft-treated (Puracol Plus) wounds as compared with previous studies of calvarium-exposed wounds healed by second intention alone; advantages of animal-derived collagen xenografts include immediate coverage of the wound, simple application, low cost, and avoidance of the morbidity associated with local flap, graft, and free flap repairs	^221,341 ^,418,419
RCM6 (resorbable collagen membrane) ■ ACE Surgical Supply	Tendon-derived type 1 bovine collagen; formaldehyde crosslinking	Level 5 Level 7a	Guides healing and regeneration of bone and surrounding tissue	Intended to aid in the wound-healing process of surgical procedures such as dental implants, bone and periodontal defects, and ridge augmentation	When used in conjunction with a bone-grafting particulate, it helps mitigate the migration of the particulate from the surgical site; fully resorbable with a resorption time of up to 6 months; integration of membrane by proliferating soft tissue, stabilization of blood clot, and host cell adhesion to membrane promote soft tissue healing	RCM6 remnants were seen in the biopsy specimen, an expected observation given that the reported resorption time is 6 months or more	^420–423
Simpurity □ SNS Medical	Wound dressing collagen particles; 100% nonbleached, native undigested bovine collagen (Sold in combination packet: Total Wound Care Solution System [TWCSS] for clinical use)	Level 5	Flexible application for wounds of different sizes and shapes; medical grade, lyophilized bovine collagen is a clean, white powder; reduces inflammation and supports tissue healing; can be used as a hemostatic dressing	Medical-grade bovine collagen comes in a clean, white powder form, making it easy to apply directly to wounds; collagen powder helps reduce inflammation and supports the healing process by providing a substrate that diverts matrix metalloproteinases (MMPs) digestion away from healing tissues; can be used as a hemostatic dressing to control bleeding.	MoA was not directly stated in peer-reviewed literature. Company claims the porous structure provides excellent absorption and scaffolding for cell proliferation and migration	Improved wound healing in patients with chronic recalcitrant wounds, infected wounds, and comorbidities	⁴²⁴
Stimulen □ Southwest Technologies Inc.	Collagen gel wound dressing; 52% collagen of long and short polypeptides along with glycerin, water, fragrance	Level 5 Level 6a Level 7a	Can be used in emergency situations not only to cover a wound but also to fill cavity wounds; gel is convenient to use, especially in places that are difficult to apply the powder form, such as the bottom of a foot	Intended for partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, donor sites and other bleeding surface wounds, abrasions, trauma wounds, and first- and second-degree burns	Serves as a substrate for high MMPs in chronic wound environment; induces polarization of healing-like macrophages in the wound, which produce anti-inflammatory and pro-angiogenic responses and promote wound healing	On day 7, histological analysis showed significant increase in the length of rete ridges, suggesting improved biomechanical properties of the healing wound tissue; modified collagen gel significantly accelerated neutrophil and macrophage recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21	^33–35,425
Stimulen Powder □ Southwest Technologies Inc.	Collagen powder; hydrolyzed modified collagens, prepared polypeptides	Level 5	When sprinkled in the wound, it interacts with exudate to form a protective gel on the wound bed; gel protects new cells and tissue from dehydration; nonadherent; does not need to be removed from the wound site; the collagen powder is readily broken down by the natural enzymes present in most wound fluids	Management of wounds including: partial- and full-thickness wounds, pressure injuries (stages I–IV), venous ulcers, diabetic ulcers, partial-thickness burns, acute wounds, abrasions, traumatic wounds healing by secondary intention, and donor sites and other surface wounds	Forms a protective gel on the wound bed that prevents dehydration and provides a scaffolding to promotes cell proliferation and ECM deposition; hydrolyzed collagen forms a better hydrogel with peptides that promotes chemotactic signaling for host cell infiltration	Application of Stimulen collagen powder (applied once daily after wound cleansing) further supported tissue regeneration by providing a scaffold for cell growth and matrix deposition	^426,427
Vergenix FG CollPlant Biotechnologies	Soft-tissue repair device; flowable gel; plant-derived recombinant human type I collagen (rhCollagen)	Level 5 Level 7b	Provides complete coverage, managing wound closure, offers a nonallergenic and a pathogen-free scaffold for safe and successful wound management	Chronic diabetic and venous wounds, pressure ulcers, traumatic injuries, and surgical wounds	Plant-derived human collagen. Scaffolds support primary human cell attachment and proliferation at an equivalent or higher level than bovine material; mixing with saline forms a collagen-fibrin matrix that enhances cell migration and tissue repair; promotes keratinocyte migration and proliferation that coincide with re-epithelialization; inflammation increased at day 1 and decreased by day 6, the induction and resolution of which helps drive the healing process	After 2 weeks of treatment, wound dehiscence was replaced with granulation tissue, and after 4 weeks, the patient was completely healed, with an acceptable aesthetic outcome of the surgical scar	^428–432
Woun’Dres □ Coloplast	Collagen hydrogel; contains polymers including carbomer and collagen; other ingredients including allantoin	Level 5	Rehydrates dry wounds and eschar; promotes moist wound environment and autolytic debridement; latex-free	Intended for dry wounds, pressure ulcers, pressure wounds, pressure sores stages II–IV, venous stasis ulcers, superficial scrapes, second- and third-degree burns, partial-thickness and full-thickness wounds, tunneling wounds, infected wounds, exuding wounds, deep cavity wounds	Dressing rehydrates dry wounds and eschar; promotes moist wound healing environment and autolytic debridement; suppress inflammation and apoptosis	Dressing promoted full-thickness excisional wound healing with scar formation; immune cell accumulation was identified in the remaining biomaterials in the wound bed	^433,434

Collagen-based products levels of evidence. Level 5 = other clinical studies (case series or studies as reference treatment, human ex vivo MoA); Level 6a = large animal with MoA; Level 6b = large animal observational; Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Table 6.

Level of evidence 7

Dressing	Composition	Level of evidence	Purpose/Claim	Use	Mechanism of action	Outcomes study/Trial	References
Collagen Gel Thermo Fisher	Tail-derived type I rat collagen	Level 7b	Clear gel providing a 3D matrix or surface coated on tissue culture plates as a substrate for culturing primary cells	Laboratory use: cell culture, co-culture, transwell assay	MoA was not directly stated in peer-reviewed literature. Company claims that rat tail collagen type I can be prepared as a clear gel providing a 3D matrix or surface coated on tissue culture plates as a substrate for culturing primary cells	TGF-β1 treatment of cultured human Tenon’s fibroblasts in collagen gel showed contraction by reduction in collagen gel size	^435–437
Puracol Ultra ECM □ Medline	Porcine mesothelium; decellularized, lyophilized, and sterilized porcine peritoneal membrane; contains types I, III, IV collagen; other proteins, including fibronectin, proteoglycans, laminin, elastin, fibroblast growth factors (FGF-b)	Level 7b	Has a significantly higher impact on new blood vessel formation compared with leading ovine collagen ECM and leading collagen/ORC	Completely bioabsorbable dressing is naturally incorporated into the wound over time. High retention of growth factors (FGF-basic, vascular endothelial growth factor [VEGF], and TGF-β1) after the decellularization process, high angiogenetic potential in vitro and MMPs-inhibition to modulate inflammation while promoting healing.	MoA was not directly stated in peer-reviewed literature. Company claims that Puracol Ultra ECM inhibits proteolytic activity and retains collagen networks that highly resemble dermis structures that may contribute to positive wound healing outcomes; high elastin content which can induce cell migration and proliferation; retention and slow release of soluble growth factors (FGF-basic, VEGF, and TGF-β1) promotes angiogenic micro-vessel formation; growth factor retention also promotes host cell adhesion and proliferation; matrix MMP binding suppresses inflammatory state and supports proliferation	Showed comparatively high levels collagen and elastin (vs other grafts and biomaterials), and promoted micro-vessel formation; porcine mesothelium has the potential to be used as a wound healing material, considering its composition, resistance to enzymatic degradation, cytocompatibility, and angiogenic potential; a biofilm model showed that nanozeolite-entrapped antimicrobials have potential for alleviating biofilm-infected wounds	^341,418,438

Collagen-based products levels of evidence. Level 7a = small animal with MoA; Level 7b = small animal observational and in vitro. FDA status: □ - cleared; ■ - approved.

Skin substitutes

Natural wound healing re-establishes a barrier between vulnerable inner tissues and an environment full of harmful substances and pathogens. Skin is the body’s first line of defense against environmental factors. Disrupting this barrier through wounds or disease exposes the body to risk of infection, which is exacerbated in individuals with compromising medical conditions such as diabetes and obesity.⁴³⁹ The ability to restore damaged skin with surgical intervention dates back 2,600 years ago. The “father of plastic surgery,” Sushruta, was an innovative surgeon in Kashi, India in the year 600 BCE.⁴⁴⁰ He was renowned for reconstructive surgeries, such as utilizing cheek flaps for nose reconstruction, as well as developing a code of medical ethics. Grafting techniques progressed steadily in the 19th and 20th centuries, leading to a profound breakthrough in 1981 when John Burke and colleagues developed an artificial skin substitute with a top layer of silicone polymer and bottom layer of crosslinked collagen and glycosaminoglycans (GAGs).⁴⁴¹ This provided the foundation for tissue engineering techniques that led to modern collagen-based products designed for biocompatibility, while establishing a structural framework to promote more efficient tissue growth, reduce inflammatory response, maintain a moist environment, and inhibit microbial infection.

The first U.S. FDA approved skin substitutes were TransCyte (Advanced Tissue Science, La Jolla, CA) and Dermagraft (developed by Advanced Tissue Sciences, now marketed by Organogenesis Inc., Canton, MA). These products consisted of a polymer mesh scaffold on which human fibroblasts were cultured which secreted collagen, along with other ECM proteins, growth factors, and cytokines, to support skin wound healing. In the case of TransCyte, the scaffold includes a silicone membrane and the tissue was frozen to kill the cells and allow storage.⁴⁴² Dermagraft was cryopreserved and the cells retained some viability.⁹⁵ As dressings, they are indicated for partial thickness burns, surgical wounds, and diabetic foot ulcers without tendon, muscle, or bone exposure, providing improved patient wound healing outcomes compared with standard of care.^272,442 More recent dressings have drifted away from the necessity of culturing live human fibroblasts, rather, developing dressings comprised of collagen has increased the shelf-life, long-term stability, and shortened preparation time prior to use, while still promoting wound healing outcomes. Combining modern collagen-based biomaterials with growth factors is an approach being used to support tissue regeneration in chronic wounds. For example, VEGF fused with a collagen-binding domain has been incorporated into a collagen-based biomaterial to essentially create a slow-release drug delivery system that promotes angiogenesis and revascularization of chronic diabetic wounds.⁴⁴³ Similar methods have been developed for collagen-B-cell leukemia/lymphoma 2-adipose-derived stem cell scaffolds,⁴⁴⁴ collagen-copper/cobalt bioactive microfibrous glass mats,⁴⁴⁵ and collagen matrix hydrogel delivery of basic fibroblast growth factor (bFGF).⁴⁴⁶ Puracol Ultra ECM has also been used to deliver FGF to promote regenerative wound healing in a small animal aortic ring assay.⁴⁴⁷

Cardiovascular collagen

Defects in collagen from mutations in the collagen type I/III genes can be responsible for cardiovascular diseases and abnormalities such as aortic dilation, aortic aneurysms, arterial dissection, and rupture.⁴⁴⁸ While defects in collagen can result in cardiovascular abnormalities, tissue engineered collagen products can be used to treat them in vivo. The most common surgical treatments for atherosclerosis, for example, still include vascular bypass and replacement. Patents with atherosclerosis, however, often have poor vein and artery health, making them poor candidates for autograft harvesting. Collagen-based vascular grafts have become alternative materials for transplantation when combined with other natural (fibrin, elastin) or synthetic (polyurethane, polydioxanone, polycaprolactone) materials, which can bolster collagen’s mechanical properties without diminishing the beneficial biocompatibility, cell adhesion, biodegradability, hydrophilicity, and weak immunogenicity properties of collagen.⁴⁴⁹ Dacron vascular grafts, for example, when coated with collagen have long-term secondary corrected 8-year patency rates >90%.⁴⁵⁰ Collagen engineered vascular products can also be utilized as drug delivery systems with VEGF and bFGF, promoting post-transplant endothelialization while limiting thrombosis and intimal hyperplasia.⁴⁵¹ In the case of bFGF delivery, heparinized collagen-coated vascular grafts (with embedded heparin) resulted in long term patency by mimicking the mechanism of heparin sulfate present in native ECM of endothelial cells that binds and stabilizes bFGF, releasing it upon vascular wall damage, resulting in localized bFGF release and proliferation of endothelial cells.⁴⁵¹ Antibiotics and antimicrobial peptides have also been incorporated into collagen-based vascular grafts to prevent perioperative infection.⁴⁵² Collagen-based hydrogels have also been used as an injectable therapeutic to prevent myocardial infarction by providing ventricular wall thickness and mechanical support without hindering myocardial contraction. Studies have shown, however, that there is a therapeutic window post-myocardial infarction when this treatment is most beneficial because of pathophysiological stages of necrosis, inflammation, proliferation, and maturation.^453,454 These collagen hydrogels have also been used as delivery systems for therapeutic drugs and stem cells to treat cardiovascular disease.⁴⁴⁹ Akin to hydrogels, collagen-based patch scaffolds have been developed to serve as epicardial dressings for reconstruction of large cardiovascular defects. These dressings can be loaded with conductive material, bioactive drugs, stem cells, and exosomes to facilitate the reconstruction and regeneration of large cardiac and vascular defects.⁴⁴⁹

SKIN HEALTH

Skin collagen synthesis

Skin, the body’s largest organ, structurally serves as a protective barrier against environmental stressors and damage. The importance of maintaining skin health throughout one’s lifetime has become a more widely accepted practice as awareness has spread of skin cancer as being the most diagnosed cancer in the world that is also preventable.⁴⁵⁵ Evidence for age-related weakened barrier functions has also supported the need for healthy skin practices.⁴⁵⁶ Photoaging, caused by prolonged exposure to extrinsic ultraviolet (UV) radiation, has not only been identified as one of the main risk factors for melanoma, but also has a profoundly detrimental effect on ECM deposition in the dermis.⁴⁵⁷ Photoaging causes fragmentation and degradation of collagen, the main structural component of ECM.^458,459 Disruptions in collagen synthesis have been correlated with a spectrum of diseases that have been traced back to over 1,000 mutations in patients.⁴⁶⁰ Heritable genetic disorders have been identified that cause disrupted collagen fibril formation in skin biopsies.⁴⁶¹ Ehlers-Danlos Syndrome, for example, is one such disorder mostly attributed to mutations in COL5A1 and COL5A2 genes, and in rare cases COL3A1. Resulting haploinsufficiency of type V collagen can manifest symptoms in varying degrees of severity from mild to fatal, including skin hyperextensibility, joint hypermobility, tissue fragility, delayed wound healing and atrophic scarring, and vascular ruptures.^462–467

Skin collagen is primarily derived from triple helix procollagen produced by fibroblasts.¹⁵ Collagen turnover occurs at different rates in different tissues, with a half-life of skin collagen (insoluble) of approximately 15 years, whereas cartilage collagen half-life can reach 117 years.⁴⁶⁸ Endogenous synthesis of skin collagen studies in 1964 revealed glycine as the most abundant amino acid making up its triple helical structure.^469,470 Further study has shown that collagen’s amino acid composition is roughly 1/3 glycine, 0.7/3 proline (+hydroxyproline), and 1.3/3 other amino acids, and that limiting glycine and proline limits maximal collagen synthesis,⁴⁷¹ with proline biosynthesis as a rate limiting factor.⁴⁷² Glycine, proline, and hydroxyproline have now made their way into global markets in the form of hydrolyzed collagen peptides present in wound dressings, as well as skin care and food products.

Topical collagen applications

Topically applied collagen products are becoming more popular in skin care markets. However, topical applications of intact collagen capable of replacing endogenous collagen within the skin is a common misconception. Native collagen that has been topically applied has poor permeability and cannot penetrate the skin barrier.⁴⁷³ When hydrolyzed, even collagen peptides larger than six to seven amino acids cannot be efficiently absorbed (Fig. 3).⁴⁷⁴ One of the most common used topical collagen products is hydrolyzed collagen tripeptide (CTP) sequence Gly-X-Y (often Gly-prolyl-hydroxyproline [Pro-Hyp]). It is an abundantly available biological material that has low allogeneic properties, making it a desirable component for topical and oral collagen-based products.⁴⁷⁵ The application of CTP has been considered to contribute to smoothing of facial wrinkles and improving skin elasticity; however, these observations are also coupled with increased moisture content. Collagen is hygroscopic (attracts water), so when applied topically, it forms a moisturizing film that plumps the skin, reducing fine lines temporarily. It may also temporarily strengthen the skin barrier, preventing moisture loss (e.g., in dry or aged skin). High-molecular-weight collagen (in creams/sheets) may sit on the skin’s surface, creating an optical smoothing effect—similar to silicone scar sheets.⁴⁷⁶ Some hydrolyzed collagen peptides (small fragments) can arguably signal fibroblasts (skin cells) to boost collagen and elastin synthesis (via transforming growth factor-β [TGF-β] and other growth factors).⁴⁷⁶ Some collagen products may have antioxidant properties that neutralize free radicals (reducing UV-induced damage).⁴⁷⁴ Most of these plausible mechanisms require rigorous testing in appropriately designed clinical trials. The hype for such cosmetic and aesthetic products in the market seems to be frequently generated by aggressive marketing strategies not supported by rigorous science. Appropriate consumer caution and due diligence are thus warranted.

Collagen-based fillers

Collagen injections have been a trend in cosmetic research to fill facial voids, enhance volume and remove wrinkles. Conceptually, collagen injections in the mid-to-deep layers of the skin act as support structures that remove wrinkles and skin folds. Products claim that injected collagen is absorbed within a month of injection and replaced by native de novo synthesized collagen by 3 months postinjection.^477,478 Rigorous clinical studies are necessary to support these claims. Recent retrospective analysis of clinical data for facial wrinkles treated with collagen type III injections showed significant improvement in experimental subjects compared to control subjects at 30 days postinjection.⁴⁷⁹ Ninety days postinjection, however, there was no significant difference between the groups, suggesting that the collagen filler was broken down and resorbed rather than replaced.⁴⁷⁹ Individuals considering use of collagen dermal fillers should also be cautioned that mild to severe complication risks have been associated with their use, including discoloration, necrosis, infection, vision loss, granuloma formation, foreign body reaction, and biofilm formation.^480,481 Because of potential adverse events, including autoimmune response, which required sensitivity reaction testing, several collagen fillers (including Zyderm, Zyplast, Cosmoderm, Cosmoplast) have been discontinued.^399,400 Noncollagen dermal fillers have also been developed as potentially safer or longer lasting alternatives. Injectable poly-L-lactic acid (PLLA), HA, calcium hydroxyapatite (CaHA), polymethyl methacrylate (PMMA), polyalkylimide, and silicone implants have been used to varying degrees of success.^263,482 Challenges and complications vary depending on biodegradable (PLLA, HA, CaHA) and nonbiodegradable (PMMA, polyalkylimide, silicone) properties.⁴⁸³ Because of the short-term effects of collagen fillers that are typically depleted 3–4 months postinjection, HA has become a more commonly used alternative which can last 12–24 months.⁴⁸⁴ Collagen and HA dermal fillers currently have in vivo mechanisms of action that are not fully understood, as well as short and long-term complication risks that should be discussed with physicians before injection procedures. Additional rigorous scientific studies are required.

ORTHOPEDICS AND DENTAL APPLICATIONS

Tendon repair

Collagen-based scaffolds and matrices are used in bone grafts, cartilage repair, and tendon or ligament reconstruction (Fig. 2). They serve as a scaffold that promotes the regeneration of bone and soft tissues in joint repairs and spinal surgeries. Sports injuries, for example, are often associated with bone and tendon injury as a result of overuse or trauma. Tendons are connective tissues with a multitude of organized collagen fiber bundles.⁴⁸⁵ Tendon injuries are painful and typically slow to heal, even when treated with nonsurgical drug, stem cell, or physical therapies.⁴⁸⁶ bFGF can aid in accelerated tendon healing by promoting neovascularization during the pro-inflammatory phase, while also stimulating fibroblast production of type III/I collagens during the cell proliferation phase of healing. Overuse of bFGF can overstimulate these processes however, leading to fibrotic scar formation and potential tendon adhesions.⁴⁸⁷ A common musculoskeletal disability that occurs in approximately 8% of adults is rotator cuff damage, resulting from acute tear injuries or age-related degeneration.⁴⁸⁸ The use of acellular scaffolding, such as GraftJacket, retains intact collagen ECM and blood vessel channels with low immunogenicity.^296,297 These acellular dermal matrices show promising results in repairing large rotator cuff tears in patients, with little to no adverse events.²⁹⁷ Another application of collagen-based products to support orthopedic regeneration comes from the use of dehydrated human placental allograft amnion-chorion membrane material (NuShield) that retains collagens, ECM proteins, growth factors, elastin, glycoproteins, and proteoglycans.³⁰⁵ When applied to tendon, spinal or nerve damage, placental allografts release growth factors and cytokines to promote fibroblast and keratinocyte migration and proliferation, while paracrine signaling subsequently regulates localized inflammatory responses.³⁰⁵ This dehydrated placental allograft material has shown promising results as regenerative treatments for tendons, nerves, spinal adhesions, and fibrosis, as well as treatment for chronic wounds.^489,490

Bone grafting

Bone repair is a major challenge in the musculoskeletal regenerative therapy field. Common bone defects are the result of osteoporosis weakening of bones, traumatic fractures and breaks, osteomyelitis, periodontitis, congenital defects, and hereditary diseases.⁴⁹¹ Mutations in the COL1A1 and COL1A2 genes can result in multiple subtypes of osteogenesis imperfecta or “brittle bone disease.”⁴⁶⁷ The lack of suitable donors for bone grafting is compounded by the risk of immune rejection, while autologous bone grafting is limited by the patient’s own available donor material, which also carries the risk of causing irreversible damage when harvested. The application of collagen-based biomaterials provides a matrix for cell infiltration and proliferation that, when combined with porous material and factors such as connective tissue growth factor (CTGF) or bone morphogenic proteins (BMP), establish an osteogenic microenvironment that promotes osteoblast deposition of bone matrix.^492,493 Recent clinical trials have shown that the use of calcium phosphate cement is useful in reducing fractures and pain while improving functional outcomes.⁴⁹⁴ However, limited osteoinductivity and resulting tensile strength make it an undesirable void filler for larger defects.⁴⁹⁴ Biomaterials have been making significant progress as alternative bone void filler options that contain collagen to promote bone healing processes. A combination of calcium phosphate, dibasic (DICAL), and purified type 1 bovine collagen (CopiOs) has been used as an osteoconductive sponge scaffold to promote regeneration of bone voids (Table 3). The DICAL-collagen product, when coated with BMP, has shown success in filling post-harvest iliac crest donor sites in spinal fusion surgery and in promoting bone growth in large tibial defects in animal models by creating a microenvironment that supports osteogenesis.³⁴⁶ This approach is designed to mitigate donor site risk complications of morbidity (9.4 − 49%) and chronic pain at iliac crest autograft harvest sites.^495–499 Combining collagen-based biomaterial (Healos) with bone marrow aspirate (BMA), that has undergone selective cell retention of mesenchymal stem cells (MSCs), has produced a substitute for autologous iliac crest bone grafts in lumbar spinal fusion procedures.³⁸² Strips of this biomaterial loaded with MSCs and CTGF have been implanted in posterolateral fusion procedures in 21 patients, 100% of which achieved successful solid bilateral fusions.³⁸² For the treatment of long bone fractures, porous beads comprised of hydroxyapatite, tricalcium phosphate ceramic, and fibrillar type 1 bovine collagen (CollaGraft) have been developed to create a biodegradable osteoconductive scaffold.²⁵³ When preloaded with BMA, this biodegradable scaffold has been used successfully to promote bone repair in patients with long bone fractures.^253,254 This combination has also shown promise as an autologous bone graft substitute in large animal models.²⁵⁵ The use of collagen-based biomaterials for treatment of bone damage has proven to be beneficial in repairing small bony voids and long bone fractures, as well as providing scaffold and osteogenic support for bone fusion procedures (Tables 1–6). These same principles have been used to promote wound healing and bone regeneration in oral and maxillofacial surgeries.

Dental applications

Collagen membranes and graft materials are used in oral surgery, particularly for periodontal regeneration and guided bone regeneration (Fig. 2). Periodontal disease, or gum disease, commonly refers to inflammatory disorders ranging from mild reversible gingivitis to the more severe irreversible periodontitis gum infection that causes loss of connective tissue and bone support, often leading to tooth loss.⁵⁰⁰ Beyond causes such as plaque buildup, periodontal disease has been defined as a systemic disease associated with a host of other morbidities.⁵⁰¹ Severe periodontitis reached a prevalence of 23.6% in dentate adults in 2020, which is striking when considering that periodontitis is the medical basis for roughly 25–38% of tooth extractions.⁵⁰² To promote better healing and recovery following dental surgery procedures, researchers have been developing collagen-based materials that promote clotting, tissue regeneration, and bone preservation. The use of bioabsorbable collagen membranes in periodontal regeneration procedures also prevents the need for membrane removal surgery while also limiting the risks of bacterial colonization.⁵⁰³

An absorbable porous collagen sponge material (CollaCote) is beneficial as a collagen-based product that can be packed into a root canal space following debridement, along with a barrier of mineral trioxide aggregates (Table 2). This collagen matrix is fully absorbed in 10–12 days and promotes obturation, or closure, of the canal space through host cell migration and osteoinductivity into homogeneously spaced micropores.^246,247 After tooth extraction, applying a biodegradable collagen plug (CollaPlug) before socket suturing has been shown to reduce postoperative bleeding and pain. The plug acts as a hemostatic material by absorbing fluids, enhancing clot formation, and accelerating granulation tissue development.³⁴¹ The same collagen plug has demonstrated, with the addition of platelet rich fibrin, that it contributes to alveolar ridge preservation in extraction sockets, preserving bone width for up to 4 months.³⁴² Animal studies have shown that fibrillar collagen (CollaTape) promotes early phases of bone healing through osteoblast surface fibronectin-mediated adhesion and collagen-driven angiogenesis.²⁴⁸ This effect was limited by the degradation of collagen dressing within 5 weeks of application. Longer-term ridge preservation could be achieved by adding synthetic bone particles to the extraction socket prior to closing the wound with collagen dressing.

Other collagen products used in oral surgery are applied to cover socket void fillers as a membranous sheet. For example, a non-crosslinked bilayer collagen membrane osteophilic matrix (Bio-Gide) has a film layer designed to prevent soft tissue invasion into the socket, thus promoting alveolar ridge preservation and bone regeneration.^133,504 A comparable product with a sugar crosslinked collagen membrane (Ossix Plus) prevented host cell infiltration⁴⁰⁹ (Tables 1, 5). The noncrosslinked structure of collagen membranes (Bio-Gide) promoted angiogenesis and vascularization in the wound; whereas crosslinked collagen membranes (Ossix Plus) were not permissive for angiogenesis, yet still allowed nutrient permeation.⁴¹⁰ Filling extraction sockets with deproteinized bovine bone mineral and 10% porcine type 1 collagen (Bio-Oss) prior to sealing with extraction sockets with noncrosslinked bilayer collagen membrane (Bio-Gide) significantly improved bone height and width preservation for 6 months postextraction.¹³³ The use of collagen products singly, or in combination, can preserve alveolar bone which otherwise would undergo the healing-induced remodeling and volumetric loss of socket contour post-tooth extraction.¹³³ Thus, use of these collagen products may preserve alveolar ridge necessary for subsequent dental implants without the need for additional bone grafting.

COLLAGEN AS DIETARY SUPPLEMENT

The greatest proportion of collagen products currently resides with the food industry, reaching just over 55% of the total U.S. collagen market in 2024, followed by medical products. The food industry use of collagen shows up in a variety of forms from the casings around sausages, to thickening agents such as gelatin that are used to increase viscosity or as a way of regulating flavor release.^505,506 Collagen is also used in the food preservation industry to prevent water loss from meat during freezing/thawing and even shows up in ice cream products to prevent ice crystal formation. With such a large portion of the multi-billion-dollar collagen market being dedicated to the food industry, an important question comes to the forefront: Is collagen beneficial to eat?

Collagen supplements are showing up in food and beverage products across the globe, with claims of a variety of health benefits (Fig. 2). Predominantly found in connective tissues such as skin, cartilage, and bone, cartilage is recognized as source of fiber and protein. Protein Digestibility-Corrected Amino Acid Score evaluation following World Health Organization guidelines marks collagen as an incomplete protein source because of lack of tryptophan. Even so, peptides can substitute up to 36% of the daily protein requirements in the Western diet.⁵⁰⁷ This means that, while collagen cannot be used as a complete protein substitute, it may be a safe dietary supplement when used up to approximately one-third of a mixed protein diet.

One of the common health benefits advertised for ingested collagen products is healthier, more elastic skin with reduced wrinkle lines. It is unclear, however, what direct mechanisms of action may be responsible for these proclaimed benefits. There have been studies that make correlations between ingesting collagen bioactive dipeptides (Pro-Hyp and Hyp-Gly) or tripeptides (Gly-X-Y) and increased skin water content.^508–511 There is also evidence that oral ingestion of collagen peptides increases natural moisturizing factors in the stratum corneum including urea, lactic acid, filaggrin-derived amino acids, pyrrolidone carboxylic acid, and urocanic acid.^512,513 However, these observations did not show that ingestion of bioactive collagen peptides have an effect on collagen production, or retention of native collagen, within the skin.

Randomized controlled trials (RCTs) have shown that the ingestion of collagen hydrolysates and hydrolyzed collage-based supplements have a beneficial effect on wound healing for patients with burn wounds or pressure ulcers, respectively.^514,515 More recently, collagen peptides administered in combination with omega-3 fatty acids have been suggested as oral supplements with the potential to improve inflammatory responses and dysbiosis in burn patients. An RCT was performed on burn patients to determine if ingested collagen peptides were beneficial to regulate gut microbiome colonization, acting as a preventative treatment for dysbiosis. Patients did not, however, have any significant changes in Lactobacillus, Enterobacteriaceae, or F. prausnitzii concentrations between treatment groups.⁴⁴⁷ The mechanism for how ingested collagen is utilized for therapeutic benefit in wound healing or skin elasticity has not yet been defined, yet there are still strong correlative findings in experimental trials.^{475,514–516} Rigorous scientific studies are needed. It is unlikely that ingested collagen is incorporated directly, for example, into the dermis to supplant and replace regions of damaged or degrading collagen. It seems much more likely that once ingested, collagen is digested down to amino acids and short peptides that can circulate and be utilized by regenerative processes as base material for de novo collagen synthesis.

Oral collagen consumption has also been investigated for benefits independent of skin elasticity and wound healing. Ingestion of undenatured type II collagen can result in an oral immune tolerance response that can serve as a therapeutic treatment for autoimmune inflammatory disease, such as rheumatoid arthritis.⁵¹⁷ Oral immune tolerance can occur through multiple mechanisms, which begin with microfold epithelial cells (in Peyer’s patches of the gut-associated lymphoid tissue) transporting ingested antigens across the mucosal barrier.^518,519 Antigen presenting cells in the Peyer’s patches associate with T cells, which in turn circulate to mesenteric lymph nodes and, subsequently, to the peripheral immune system.⁵²⁰ T cells activated by type II collagen enter the blood stream and secrete anti-inflammatory cytokines TGF-β, IL-4, and IL-10 when in contact with articular cartilage.⁵¹⁸ This mechanism may result in a bystander effect that inhibits T helper (Th)1 response in arthritic lesions. Rigorous RCTs are required. Oral collagen has also shown potential benefits in cartilage degenerative conditions such as osteoarthritis. In a canine model of osteoarthritis, ingestion of undenatured type II collagen markedly reduced arthritic pain through a mechanism of action independent from glucosamine hydrochloride and chondroitin sulfate.⁵²¹ In a clinical trial, osteoarthritis patients receiving undenatured type II collagen oral doses over a 12-week period exhibited significant improvement in knee flexibility and mobility as well as reduced knee and back pain.⁵²² This same principle has held true in clinical studies with healthy individuals that have activity-related joint discomfort. Treatment with undenatured type II collagen oral supplements resulted in improved knee joint range of motion flexibility and extensibility.⁵²³

Oral consumption of enzymatically decomposed collagen peptides and tripeptides have also been correlated with improvement in hair condition (Fig. 3). In ex vivo human culture and in vivo animal models, oral collagen peptides activated the tissue homeostasis regulating canonical Wingless-related integration site (Wnt) (Wnt/glycogen synthase kinase-3β/β-catenin) signaling pathways and stimulated growth factor (insulin-like growth factor binding protein-6, PDGF-AB, placental growth factor, VEGF, keratin27, Gprc5d, Ki67) expression.^524,525 This mechanism was associated with proliferation of human dermal papilla and outer root sheath cells, as well as human hair follicle elongation and increased hair growth. While this mechanism has not been shown in patients, it does provide insight into collagen peptide signaling mechanisms and the broader range of impacts oral collagen supplements may have in the body. These findings are promising but not definitive. Rigorous clinical studies are required.

TAKE HOME MESSAGES

Wound Healing and Collagen-Based Products

Collagen is the dominant structural protein (25–30% of total body protein), with types I and III being most abundant in skin (80–85% and 8–11%, respectively).⁵⁴⁹

Mechanisms of Action

Historical Milestones: ◦

1981: First commercial collagen dressing (CollaDerm, Integra LifeSciences).

◦

1985: Instat (collagen sponge for hemostasis, J&J).

◦

1996: Integra dermal regeneration template (DRT) (collagen-GAG template for burns).

◦

2000: ColActive (bovine collagen dressing by SouthWest Technologies).

◦

2002: Promogran (collagen-cellulose matrix for chronic wounds, J&J, now Solventum).

Mechanisms of Action ◦

Provides scaffold for tissue growth, reduces inflammation, maintains moist wound environment.

◦

Regulates mechanisms associated with diabetic ulcers, venous stasis ulcers, and pressure ulcers.

Collagen-Based Dressings and Innovations

Types of Collagen Dressings: ◦

Films (adherent, for small wounds)

◦

Sponges (absorbent, for high-exudate wounds)

◦

Hydrogels (moisture-retentive, nonadherent)

◦

Powders (for exudate absorption)

◦

Acellular scaffolds (e.g., fish skin grafts—low immunogenicity).

Emerging Technologies ◦

3D-printed collagen skin (Pandorum Tech).

◦

Recombinant human collagen (CollPlant’s plant-based rhCollagen).

◦

Phage-integrated dressings (target MRSA/Pseudomonas).

Regenerative Medicine and Skin Substitutes

Skin Substitutes: ◦

Dermagraft (living fibroblast scaffold) and Integra DRT (collagen-GAG matrix) improve healing in burns/diabetic ulcers.

◦

Growth factor–collagen combos (e.g., VEGF + collagen) enhance angiogenesis.

Cardiovascular: ◦

Collagen-coated vascular grafts (e.g., Dacron) show >90% patency at 8 years

◦

Injectable collagen hydrogels support post-heart attack repair.

Topical and Injectable Collagen

⚠ Topical Collagen Does NOT Replace Skin Collagen ◦

Large molecules cannot penetrate skin but may: ▪

Hydrate (temporarily plumps skin)

▪

Signal fibroblasts (via peptides like Gly-Pro-Hyp).

▪

Provide antioxidant protection

Injectable fillers ◦

Short-term effects (absorbed in 1–3 months)

◦

Risks: Granulomas, necrosis, biofilm formation

◦

Alternatives: Hyaluronic acid (lasts 12–24 months)

Orthopedics and Dental Applications

Tendon/Bone Repair ◦

Acellular collagen scaffolds (e.g., GraftJacket) aid rotator cuff healing

◦

Collagen + BMP promotes bone growth in spinal fusion/tibial defects

Dental Uses ◦

CollaPlug: Reduces postextraction bleeding/pain

◦

Collagen membranes (e.g., Bio-Gide) preserve alveolar bone for implants.

Collagen as a Food Supplement

Limited Protein Value ◦

Incomplete protein (lacks tryptophan); max 36% of daily protein intake

◦

Claimed Benefits: skin hydration (via peptides like Pro-Hyp), but no proven collagen synthesis

◦

Joint health: Undenatured Type II collagen may reduce arthritis pain (oral tolerance mechanism).

⚠

Marketing Hype: Many claims lack rigorous clinical evidence.

Future Directions

Pipeline Innovations ◦

Biosynthetic collagen (yeast/fermentation-derived)

◦

Drug-eluting dressings (e.g., VEGF/PDGF-loaded collagen)

◦

Artificial intelligence-monitored collagen scaffolds (Integra LifeSciences).

When considering oral undenatured type II collagen supplements for personal therapeutic use, it is worth noting that not all products are created equal. Physiochemical and analytical characteristics can differ between products, with appreciable differences in color, coarseness, molecular size, and proportion of undenatured collagen to hydrolyzed collagen peptides per dose.⁵²⁶ These differences can be attributed to the mechanical processes and milling approaches used by the manufacturer.⁵²⁷ The difference in undenatured collagen per dose could have direct effects on pharmacological therapeutic benefit. Collagen as an oral supplement or therapeutic is not harmful and has several potential health-related benefits for malnutrition and inflammatory joints. However, specific uses for oral collagen supplements can often be overshadowed or sensationalized by media and advertising that boast outcomes that are not supported by rigorous science.⁵²⁸

FUTURE PERSPECTIVES

By 2030, collagen will no longer be seen as just a cosmetic ingredient—it will be a cornerstone of regenerative medicine and personalized health care. The transformation is already underway.

Wound Healing: From Passive Dressings to Bioactive Therapies: Companies are pioneering the next generation of wound care with collagen-infused calcium alginate dressings that not only protect wounds but actively accelerate healing.^529,530 These dressings maintain a moist environment, reduce scarring, and are increasingly used outside hospital settings—empowering patients to manage recovery at home. Products enriched in specific hydrolysis of collagen will serve wound dressing functions with outcomes far superior to anything we know of today. Hydrolyzed collagen hydrogels, nanofibers, and sponges will promote angiogenesis, reduce inflammation, and stimulate tissue regeneration.^529,531 These materials are being tailored for chronic wounds, burns, and surgical recovery, with smart dressings on the horizon that can release drugs or signal infection in real time.^532,533

Skincare: From Anti-Aging to Skin Regeneration: In the consumer space, collagen is evolving from a buzzword to a bioactive ingredient with clinically validated benefits. Topical formulations are being enhanced with collagen peptides, encapsulated delivery systems, and synergistic compounds like HA and vitamin C to improve skin elasticity, hydration, and repair.^{474,534–536} The next frontier is personalized collagen skincare, where products are tailored to an individual’s skin microbiome, genetic profile, and environmental exposures.^537,538 Artificial intelligence-driven diagnostics and 3D skin printing may soon allow consumers to “print” collagen patches at home for targeted treatment.^539–541

Healthcare and Regenerative Medicine: Beyond skin, collagen is being integrated into tissue scaffolds, injectable fillers, and implant coatings to support healing in joints, bones, and internal organs.^{121,382,542–544} Innovations in recombinant collagen production and production of hydrolyzed collagen active principles—using yeast, bacteria, or even plants—are making it safer, more sustainable, and customizable for medical use.^545–547 In the near future, collagen-based biosensors may monitor healing progress or detect early signs of infection.^532,548 Combined with wearable tech, this could revolutionize postoperative care and chronic disease management.

Sustainability and Ethical Sourcing: As demand grows, the industry is shifting toward non-animal sources of collagen, including marine collagen and lab-grown alternatives.^{61,77,545,546} These options reduce the risk of disease transmission, align with ethical consumer values, and open doors for vegan-certified products.

Footnotes

ACKNOWLEDGMENTS AND FUNDING SOURCES

The authors thank the 13 peer reviewers for their critical comments that were helpful in improving this work. Relevant work in C.K.S. laboratory is supported by grants awarded to C.K.S. as PI by the U.S. Department of Defense [Grants MTEC/2019-447, MTEC/2021-425]; the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Grants DK119099, DK125835, DK128845, DK135447, DK143282, DK141513]; and the Biotech 2023-2024 PACommonwealth BT McGowan Grant.

AUTHOR DISCLOSURE AND GHOSTWRITING

Chandan K Sen serves as a paid consultant for Sanara MedTech Inc as well as for SouthWest Technologies.

ABOUT THE AUTHORS

Dr. Chandan K. Sen, PhD, FNAI, is a University Endowed Professor of Surgery at the University of Pittsburgh School of Medicine. He is the director of the McGowan Institute of Regenerative Medicine and serves as the Chief Scientific Officer of the UPMC Health System’s wound care service line. He has a Google Scholar H-index of 117. Dr. Andrew Friday, PhD, is a senior scientist at the McGowan Institute of Regenerative Medicine at the University of Pittsburgh School of Medicine. Dr. Savita Khanna, PhD, is a Professor at the at the McGowan Institute of Regenerative Medicine at the University of Pittsburgh School of Medicine. Her laboratory specializes on neurodegeneration and neuropathy with emphasis on rescue. Dr. Sashwati Roy, PhD, is a tenured Professor at the at the McGowan Institute of Regenerative Medicine at the University of Pittsburgh School of Medicine. Her program focuses on wound inflammation and biofilm infection. She is a principal investigator of the NIDDK-Diabetic Foot Consortium.

Abbreviations and Acronyms

References

GrandViewResearch. Collagen Market Size To Reach $18.7 Billion By 2030. Press Release. February, 2025. Available from: https://www.grandviewresearch.com/press-release/global-collagen-market

Hawthorne

, Simmons

, Stuart

, et al. Enhancing wound healing dressing development through interdisciplinary collaboration. J Biomed Mater Res B Appl Biomater, 2021; 109(12):1967–1985; doi: 10.1002/jbm.b.34861

Taupin

, Gandhi

, Saini

. Integra(R) dermal regeneration template: From design to clinical use. Cureus, 2023; 15(5):e38608; doi: 10.7759/cureus.38608

Greer

, Foman

, Dorrian

, et al. Advanced wound care therapies for non-healing diabetic, venous, and arterial ulcers: a systematic review. In: Appendix A, Therapy Descriptions and References. Department of Veterans Affairs (US): Washington (DC); 2012.

Mathew-Steiner

, Roy

, Sen

. Collagen in wound healing. Bioengineering (Basel), 2021; 8(5):63; doi: 10.3390/bioengineering8050063

Pena

, Martin

. Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol, 2024; 25(8):599–616; doi: 10.1038/s41580-024-00715-1

Xue

, Jackson

. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. Adv Wound Care (New Rochelle), 2015; 4(3):119–136; doi: 10.1089/wound.2013.0485

Landen

, Li

, Stahle

. Transition from inflammation to proliferation: A critical step during wound healing. Cell Mol Life Sci, 2016; 73(20):3861–3885; doi: 10.1007/s00018-016-2268-0

White

, Cutting

. Critical colonization--the concept under scrutiny. Ostomy Wound Manage, 2006; 52(11):50–56.

10.

Roy

, Sen

. MiRNA in innate immune responses: Novel players in wound inflammation. Physiol Genomics, 2011; 43(10):557–565; doi: 10.1152/physiolgenomics.00160.2010

11.

Sinha

, Sen

, Singh

, et al. Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nat Commun, 2018; 9(1):936; doi: 10.1038/s41467-018-03208-w

12.

Roy

, Sen

. miRNA in wound inflammation and angiogenesis. Microcirculation, 2012; 19(3):224–232; doi: 10.1111/j.1549-8719.2011.00156.x

13.

Caley

, Martins

, O’Toole

. Metalloproteinases and Wound Healing. Adv Wound Care (New Rochelle), 2015; 4(4):225–234; doi: 10.1089/wound.2014.0581

14.

Broughton

2nd , Janis

, Attinger

. The basic science of wound healing. Plast Reconstr Surg, 2006; 117(7 Suppl):12S–34S; doi: 10.1097/01.prs.0000225430.42531.c2

15.

Singh

, Rai

, Agrawal

. Regulation of Collagen I and Collagen III in Tissue Injury and Regeneration. Cardiol Cardiovasc Med, 2023; 7(1):5–16; doi: 10.26502/fccm.92920302

16.

Onursal

, Dick

, Angelidis

, et al. Collagen biosynthesis, processing, and maturation in lung ageing. Front Med (Lausanne), 2021; 8:593874; doi: 10.3389/fmed.2021.593874

17.

Ishikawa

, Bachinger

. A molecular ensemble in the rER for procollagen maturation. Biochim Biophys Acta, 2013; 1833(11):2479–2491; doi: 10.1016/j.bbamcr.2013.04.008

18.

Kadler

, Holmes

, Trotter

, et al. Collagen fibril formation. Biochem J, 1996; 316 (Pt 1)(Pt 1):1–11; doi: 10.1042/bj3160001

19.

Vallet

, Ricard-Blum

. Lysyl oxidases: From enzyme activity to extracellular matrix cross-links. Essays Biochem, 2019; 63(3):349–364; doi: 10.1042/EBC20180050

20.

Sen

. Wound healing essentials: Let there be oxygen. Wound Repair Regen, 2009; 17(1):1–18; doi: 10.1111/j.1524-475X.2008.00436.x

21.

Hopf

, Gibson

, Angeles

, et al. Hyperoxia and angiogenesis. Wound Repair Regen, 2005; 13(6):558–564; doi: 10.1111/j.1524-475X.2005.00078.x

22.

Allison

, Armstrong

, Goodney

, et al.; American Heart Association Council on Peripheral Vascular Disease; Council on Hypertension; and Council on Lifestyle and Cardiometabolic Health. Health disparities in peripheral artery disease: A scientific statement from the American Heart Association. Circulation, 2023; 148(3):286–296; doi: 10.1161/CIR.0000000000001153

23.

Krizanova

, Penesova

, Hokynkova

, et al. Chronic venous insufficiency and venous leg ulcers: Aetiology, on the pathophysiology-based treatment. Int Wound J, 2023; 21(2):e14405; doi: 10.1111/iwj.14405

24.

Kalani

, Brismar

, Fagrell

, et al. Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers. Diabetes Care, 1999; 22(1):147–151; doi: 10.2337/diacare.22.1.147

25.

Sen

, Roy

. OxymiRs in cutaneous development, wound repair and regeneration. Semin Cell Dev Biol, 2012; 23(9):971–980; doi: 10.1016/j.semcdb.2012.09.012

26.

Carter

, DaVanzo

, Haught

, et al. Chronic wound prevalence and the associated cost of treatment in Medicare beneficiaries: Changes between 2014 and 2019. J Med Econ, 2023; 26(1):894–901; doi: 10.1080/13696998.2023.2232256

27.

Sen

. Human wound and its burden: Updated 2022 compendium of estimates. Adv Wound Care (New Rochelle), 2023; 12(12):657–670; doi: 10.1089/wound.2023.0150

28.

Meshkin

, Zolper

, Chang

, et al. Long-term mortality after nontraumatic major lower extremity amputation: A systematic review and meta-analysis. J Foot Ankle Surg, 2021; 60(3):567–576; doi: 10.1053/j.jfas.2020.06.027

29.

Castilla

, Liu

, Velazquez

. Oxygen: Implications for wound healing. Adv Wound Care (New Rochelle), 2012; 1(6):225–230; doi: 10.1089/wound.2011.0319

30.

Han

, Ju

, Irudayaraj

. Oxygenated wound dressings for hypoxia mitigation and enhanced wound healing. Mol Pharm, 2023; 20(7):3338–3355; doi: 10.1021/acs.molpharmaceut.3c00352

31.

Berthod

, Germain

, Tremblay

, et al. Extracellular matrix deposition by fibroblasts is necessary to promote capillary-like tube formation in vitro. J Cell Physiol, 2006; 207(2):491–498; doi: 10.1002/jcp.20584

32.

Gordillo

, Sen

. Revisiting the essential role of oxygen in wound healing. Am J Surg, 2003; 186(3):259–263; doi: 10.1016/s0002-9610(03)00211-3

33.

Elgharably

, Roy

, Khanna

, et al. A modified collagen gel enhances healing outcome in a preclinical swine model of excisional wounds. Wound Repair Regen, 2013; 21(3):473–481; doi: 10.1111/wrr.12039

34.

Elgharably

, Ganesh

, Dickerson

, et al. A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds. Wound Repair Regen, 2014; 22(6):720–729; doi: 10.1111/wrr.12229

35.

Das

, Abas

, Biswas

, et al. A modified collagen dressing induces transition of inflammatory to reparative phenotype of wound macrophages. Sci Rep, 2019; 9(1):14293; doi: 10.1038/s41598-019-49435-z

36.

Zhang

, Yang

, Meng

, et al. Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats. Biochem Biophys Res Commun, 2020; 523(4):931–938; doi: 10.1016/j.bbrc.2020.01.029

37.

Pal

, Ghatak

, Singh

, et al. Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair. Nat Commun, 2023; 14(1):1129; doi: 10.1038/s41467-023-36665-z

38.

Sen

, Roy

, Mathew-Steiner

, et al. Biofilm management in wound care. Plast Reconstr Surg, 2021; 148(2):275e–288e; doi: 10.1097/PRS.0000000000008142

39.

Ganesh

, Sinha

, Mathew-Steiner

, et al. Chronic wound biofilm model. Adv Wound Care (New Rochelle), 2015; 4(7):382–388; doi: 10.1089/wound.2014.0587

40.

Roy

, Santra

, Das

, et al. Staphylococcus aureus biofilm infection compromises wound healing by causing deficiencies in granulation tissue collagen. Ann Surg, 2020; 271(6):1174–1185; doi: 10.1097/SLA.0000000000003053

41.

Schmidt

, Spino

, Roy

, et al. 311-OR: High Transepidermal Water Loss (TEWL) Associates with failure to maintain wound closure in diabetic foot ulcers. Diabetes, 2024; 73(Supplement_1); doi: 10.2337/db24-311-OR

42.

Jones

TLZ

, Holmes

, Katona

, et al. The NIDDK Diabetic foot consortium. J Diabetes Sci Technol, 2023; 17(1):7–14; doi: 10.1177/19322968221121152

43.

La Monica

, Campora

, Ghersi

. Collagen-based scaffolds for chronic skin wound treatment. Gels, 2024; 10(2):137; doi: 10.3390/gels10020137

44.

El Masry

, Chaffee

, Das Ghatak

, et al. Stabilized collagen matrix dressing improves wound macrophage function and epithelialization. FASEB J, 2019; 33(2):2144–2155; doi: 10.1096/fj.201800352R

45.

Ricard-Blum

. The collagen family. Cold Spring Harb Perspect Biol, 2011; 3(1):a004978; doi: 10.1101/cshperspect.a004978

46.

Wang

. A review of the effects of collagen treatment in clinical studies. Polymers (Basel), 2021; 13(22):3868; doi: 10.3390/polym13223868

47.

Sionkowska

, Adamiak

, Musiał

, et al. Collagen based materials in cosmetic applications: A review. Materials (Basel), 2020; 13(19):4217; doi: 10.3390/ma13194217

48.

Ghomi

, Niazi

, Ramakrishna

. The evolution of wound dressings: From traditional to smart dressings. Polymers for Advanced Techs, 2023; 34(2):520–530.

49.

Liang

, Ni

, Huang

, et al. An advanced review: Polyurethane-related dressings for skin wound repair. Polymers (Basel), 2023; 15(21):4301; doi: 10.3390/polym15214301

50.

Kaiser

, Hafner

, Mayer

, et al. Alginate dressing and polyurethane film versus paraffin gauze in the treatment of split-thickness skin graft donor sites: A randomized controlled pilot study. Adv Skin Wound Care, 2013; 26(2):67–73; doi: 10.1097/01.ASW.0000426715.57540.8d

51.

Xiao

, Chen

, Liu

, et al. Recent advances in decellularized biomaterials for wound healing. Mater Today Bio, 2023; 19:100589; doi: 10.1016/j.mtbio.2023.100589

52.

Gao

, Tan

BKJ

, Teo

JYY

, et al. Hyaluronic acid for sinonasal surgery: A systematic review and meta-analysis. Int Forum Allergy Rhinol, 2025; 15(6):616–625; doi: 10.1002/alr.23537

53.

da Silva

, Reis

, Correlo

, et al. The efficient role of sodium alginate-based biodegradable dressings for skin wound healing application: A systematic review. J Biomater Sci Polym Ed, 2024; 35(3):397–414; doi: 10.1080/09205063.2023.2289247

54.

Brumberg

, Astrelina

, Malivanova

, et al. Modern wound dressings: Hydrogel dressings. Biomedicines, 2021; 9(9):1235; doi: 10.3390/biomedicines9091235

55.

Zhang

, Geng

, Qin

, et al. Research progress and application of chitosan dressings in hemostasis: A review. Int J Biol Macromol, 2024; 282(Pt 1):136421; doi: 10.1016/j.ijbiomac.2024.136421

56.

Riabinin

, Pankratova

, Rogovaya

, et al. Ideal living skin equivalents, from old technologies and models to advanced ones: The prospects for an integrated approach. Biomed Res Int, 2024; 2024:9947692; doi: 10.1155/2024/9947692

57.

Parham

, Kharazi

, Bakhsheshi-Rad

, et al. Antimicrobial synthetic and natural plymeric nanofibers as wound dressing: A review. Adv Eng Mater, 2022; 24(6):2101460; doi: 10.1002/adem.202101460

58.

Shi

, Wang

, Song

, et al. Recent Progresses of collagen dressings for chronic skin wound healing. Collagen & Leather, 2023; 5(1); doi: 10.1186/s42825-023-00136-4

59.

Zhang

, Zha

, Huang

, et al. Sourcing, extracting, and processing collagen raw materials. In: Collagen-Based Biotextiles for Tissue Engineering. Springer; 2024; pp. 11–15; doi: 10.1007/978-3-031-71563-1_2

60.

Rezvani Ghomi

, Nourbakhsh

, Akbari Kenari

, et al. Collagen-based biomaterials for biomedical applications. J Biomed Mater Res B Appl Biomater, 2021; 109(12):1986–1999; doi: 10.1002/jbm.b.34881

61.

Cruz

, Araujo

, Avanzi

, et al. Collagen from marine sources and skin wound healing in animal experimental studies: A systematic review. Mar Biotechnol (NY), 2021; 23(1):1–11; doi: 10.1007/s10126-020-10011-6

62.

Jayaprakash

, Mohamad Abdul Razeen

, Naveen Kumar

, et al. Enriched characteristics of poultry collagen over other sources of collagen and its extraction methods: A review. Int J Biol Macromol, 2024; 273(Pt 1):133004; doi: 10.1016/j.ijbiomac.2024.133004

63.

Cheng

, Li

, Huang

, et al. Hybrid freeze-dried dressings composed of epidermal growth factor and recombinant human-like collagen enhance cutaneous wound healing in rats. Front Bioeng Biotechnol, 2020; 8:742; doi: 10.3389/fbioe.2020.00742

64.

, Jia

, Fu

, et al. The emerging progress on wound dressings and their application in clinic wound management. Heliyon, 2023; 9(12):e22520; doi: 10.1016/j.heliyon.2023.e22520

65.

Katrilaka

, Karipidou

, Petrou

, et al. Freeze-drying process for the fabrication of collagen-based sponges as medical devices in biomedical engineering. Materials (Basel), 2023; 16(12):4425; doi: 10.3390/ma16124425

66.

Buser

, Urban

, Monje

, et al. Guided bone regeneration in implant dentistry: Basic principle, progress over 35 years, and recent research activities. Periodontol 2000, 2023; 93(1):9–25; doi: 10.1111/prd.12539

67.

Qin

, Wang

, You

, et al. Collagen-based biocomposites inspired by bone hierarchical structures for advanced bone regeneration: Ongoing research and perspectives. Biomater Sci, 2022; 10(2):318–353; doi: 10.1039/d1bm01294k

68.

Merryweather

, Weston

, Roe

, et al. Exploring the microstructure of hydrated collagen hydrogels under scanning electron microscopy. J Microsc, 2023; 290(1):40–52; doi: 10.1111/jmi.13174

69.

Liang

, Huang

, Liu

, et al. Natural hydrogel dressings in wound care: Design, advances, and perspectives. Chinese Chemical Letters, 2024; 35(10):109442.

70.

, Liao

. Hydrogel wound dressings for diabetic foot ulcertreatment: Status‐quo, challenges, and future perspectives. BMEMat, 2023; 1(3):e12037; doi: 10.1002/bmm2.12037

71.

Lei

, Zhu

, Fan

. Optimization of human-like collagen composite polysaccharide hydrogel dressing preparation using response surface for burn repair. Carbohydr Polym, 2020; 239:116249; doi: 10.1016/j.carbpol.2020.116249

72.

Feng

, Zhang

, Li

, et al. Preparation of aminated fish scale collagen and oxidized sodium alginate hybrid hydrogel for enhanced full-thickness wound healing. Int J Biol Macromol, 2020; 164:626–637; doi: 10.1016/j.ijbiomac.2020.07.058

73.

Guo

, Xu

, Wang

, et al. Dramatic promotion of wound healing using a recombinant human-like collagen and bFGF cross-linked hydrogel by transglutaminase. J Biomater Sci Polym Ed, 2019; 30(17):1591–1603; doi: 10.1080/09205063.2019.1652416

74.

Shan

, Wu

. Hydrogel-based growth factor delivery platforms: Strategies and recent advances. Adv Mater, 2024; 36(5):e2210707; doi: 10.1002/adma.202210707

75.

Kallis

, Friedman

. Collagen powder in wound healing. J Drugs Dermatol, 2018; 17(4):403–408.

76.

Emami

, Ebrahimi

. Bioactive wound powders as wound healing dressings and drug delivery systems Powder. Technology, 2023:423:118501; doi: 10.1016/j.powtec.2023.118501

77.

Rakers

, Gebert

, Uppalapati

, et al. ‘Fish matters’: The relevance of fish skin biology to investigative dermatology. Exp Dermatol, 2010; 19(4):313–324; doi: 10.1111/j.1600-0625.2009.01059.x

78.

Ibrahim

, Fahmy

, Mahmoud

, et al. New strategies for sterilization and preservation of fresh fish skin grafts. Sci Rep, 2024; 14(1):1253; doi: 10.1038/s41598-024-51608-4

79.

Subhan

, Hussain

, Tauseef

, et al. A review on recent advances and applications of fish collagen. Crit Rev Food Sci Nutr, 2021; 61(6):1027–1037; doi: 10.1080/10408398.2020.1751585

80.

Kotronoulas

, de Lomana

ALG

, Karvelsson

, et al. Lipid mediator profiles of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators following seven days of treatment. Prostaglandins Leukot Essent Fatty Acids, 2021; 175:102358; doi: 10.1016/j.plefa.2021.102358

81.

Yoon

, Yoon

, Lee

, et al. Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn patients: Characterization of acellular grafts and clinical application. Int J Biol Macromol, 2022; 205:452–461; doi: 10.1016/j.ijbiomac.2022.02.055

82.

Parker

, Kaushik

, Bansal

, et al. Safety and Efficacy of Mucograft porcine collagen bioengineered acellular dermal matrix as a spacer graft in lower eyelid elevation surgery. Plast Reconstr Surg Glob Open, 2024; 12(1):e5562; doi: 10.1097/GOX.0000000000005562

83.

Liang

, Ding

, Li

, et al. A review of advanced abdominal wall hernia patch materials. Adv Healthc Mater, 2024; 13(10):e2303506; doi: 10.1002/adhm.202303506

84.

Zhong

, Chen

, Xie

, et al. A Novel UBM/SIS composite biological Scaffold for 2-year abdominal defect repairing and strength recovery in canine model. Adv Biol (Weinh), 2025; 9(1):e2400131; doi: 10.1002/adbi.202400131

85.

Skepastianos

, Mallis

, Kostopoulos

, et al. Assessment of decellularization strategy and biocompatibility testing of full-thickness abdominal wall to produce a tissue-engineered graft. Biomed Mater Eng, 2025; 36(1):43–53; doi: 10.3233/BME-240144

86.

Liu

, Lin

, Ruan

, et al. Safety and tissue remodeling assay of small intestinal submucosa meshes using a modified porcine surgical hernia model. Sci Rep, 2024; 13(1):23108; doi: 10.1038/s41598-023-50425-5

87.

Snyder

, Jana

. Strategies for development of decellularized heart valve scaffolds for tissue engineering. Biomaterials, 2022; 288:121675; doi: 10.1016/j.biomaterials.2022.121675

88.

Tuladhar

, Mulderrig

, Della Barbera

, et al. Bioengineered percutaneous heart valves for transcatheter aortic valve replacement: A comparative evaluation of decellularised bovine and porcine pericardia. Mater Sci Eng C Mater Biol Appl, 2021; 123:111936; doi: 10.1016/j.msec.2021.111936

89.

Zhang

, Tucker

, Tipton

, et al. 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside. Wiley; 2024.

90.

Willis

. Out of this W out of this world inno orld innovations - But at what cost? Inno ations - But at What Cost? Innovations in ations in Synthetic Biology Disrupt Billion-Dollar Industries. The Synapse: Intercollegiate Science Magazine, 2023; 35(1).

91.

da Gama Ferreira

, Misailidis

, Petrides

. Manufacturing of Human Collagen via Fermentation (Bio-Collagen). 2024.

92.

Aminabee

. Printing organs with 3D technology. In: Integrating Metaheuristics in Computer Vision for Real‐World Optimization Problems. Wiley: 2024;pp. 55–70.

93.

Andre-Frei

, Cadau

, Rival

, et al. Laser-Assisted bioprinted skin equivalent for cosmetic efficacy evaluation. 2019.

94.

Kaiser

. The future of multihospital systems. Top Health Care Financ, 1992; 18(4):32–45.

95.

Petit-Zeman

. Regenerative medicine. Nat Biotechnol, 2001; 19(3):201–206; doi: 10.1038/85619

96.

Parikh

, Tenenbaum

, Yan

, et al. Cortiva versus AlloDerm ready-to-use in prepectoral and submuscular breast reconstruction: Prospective randomized clinical trial study design and early findings. Plast Reconstr Surg Glob Open, 2018; 6(11):e2013; doi: 10.1097/GOX.0000000000002013

97.

Hinchcliff

, Orbay

, Busse

, et al. Comparison of two cadaveric acellular dermal matrices for immediate breast reconstruction: A prospective randomized trial. J Plast Reconstr Aesthet Surg, 2017; 70(5):568–576; doi: 10.1016/j.bjps.2017.02.024

98.

Stein

, Arnaout

, Lichtenstein

, et al. A comparison of patient-reported outcomes between Alloderm and Dermacell in immediate alloplastic breast reconstruction: A randomized control trial. J Plast Reconstr Aesthet Surg, 2021; 74(1):41–47; doi: 10.1016/j.bjps.2020.08.018

99.

Greig

, Roller

, Ziaziaris

, et al. A retrospective review of breast reconstruction outcomes comparing AlloDerm and DermaCELL. JPRAS Open, 2019; 22:19–26; doi: 10.1016/j.jpra.2019.07.005

100.

Capito

, Tholpady

, Agrawal

, et al. Evaluation of host tissue integration, revascularization, and cellular infiltration within various dermal substrates. Ann Plast Surg, 2012; 68(5):495–500; doi: 10.1097/SAP.0b013e31823b6b01

101.

Taufique

, Bhatt

, Zagzag

, et al. Revascularization of AlloDerm used during endoscopic skull base surgery. J Neurol Surg B Skull Base, 2019; 80(1):46–50; doi: 10.1055/s-0038-1666851

102.

Zelen

, Gould

, Serena

, et al. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J, 2015; 12(6):724–732; doi: 10.1111/iwj.12395

103.

Falanga

, Sabolinski

. A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen, 1999; 7(4):201–207; doi: 10.1046/j.1524-475x.1999.00201.x

104.

Stone

, Stojadinovic

, Rosa

, et al. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci Transl Med, 2017; 9(371):eaaf8611; doi: 10.1126/scitranslmed.aaf8611

105.

Falanga

, Margolis

, Alvarez

, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol, 1998; 134(3):293–300; doi: 10.1001/archderm.134.3.293

106.

Veves

, Falanga

, Armstrong

, et al.; Apligraf Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: A prospective randomized multicenter clinical trial. Diabetes Care, 2001; 24(2):290–295; doi: 10.2337/diacare.24.2.290

107.

Eudy

, Eudy

, Roy

. Apligraf as an alternative to skin grafting in the pediatric population. Cureus, 2021; 13(7):e16226; doi: 10.7759/cureus.16226

108.

Hiscox

, Li

, Gao

, et al. Nondestructive mechanical characterization of bioengineered tissues by digital holography. ACS Biomater Sci Eng, 2025; 11(2):1051–1059; doi: 10.1021/acsbiomaterials.4c01503

109.

Waymack

, Duff

, Sabolinski

. The effect of a tissue engineered bilayered living skin analog, over meshed split-thickness autografts on the healing of excised burn wounds. The Apligraf Burn Study Group. Burns, 2000; 26(7):609–619; doi: 10.1016/s0305-4179(00)00017-6

110.

Medina

, de Brugerolle de

, Chibout

, et al. Use of human skin equivalent Apligraf for in vitro assessment of cumulative skin irritation potential of topical products. Toxicol Appl Pharmacol, 2000; 164(1):38–45; doi: 10.1006/taap.1999.8875

111.

Sams

, Chen

, King

. Graftskin treatment of difficult to heal diabetic foot ulcers: One center’s experience. Dermatol Surg, 2002; 28(8):698–703; doi: 10.1046/j.1524-4725.2002.02019.x

112.

Brem

, Balledux

, Bloom

, et al. Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: A new paradigm in wound healing. Arch Surg, 2000; 135(6):627–634; doi: 10.1001/archsurg.135.6.627

113.

Oelschlager

, Pellegrini

, Hunter

, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: Long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg, 2011; 213(4):461–468; doi: 10.1016/j.jamcollsurg.2011.05.017

114.

Nockolds

, Hodde

, Rooney

. Abdominal wall reconstruction with components separation and mesh reinforcement in complex hernia repair. BMC Surg, 2014; 14:25; doi: 10.1186/1471-2482-14-25

115.

Lee

HSH

, Kwok

HHC

, Xiao

MLQ

, et al. Biosynthetic graft versus autologous graft tympanoplasty: A prospective randomized controlled trial. Eur Arch Otorhinolaryngol, 2025; 282(6):2971–2975; doi: 10.1007/s00405-024-09166-y

116.

Aho Falt

, Zawadzki

, Starck

, et al. Long-term outcome of the Surgisis((R)) (Biodesign((R))) anal fistula plug for complex cryptoglandular and Crohn’s fistulas. Colorectal Dis, 2021; 23(1):178–185; doi: 10.1111/codi.15429

117.

Sun

, Chen

, Shen

. Randomized controlled trial of lichtenstein repair of indirect inguinal hernias with two biologic meshes from porcine small intestine submucosa. Ther Clin Risk Manag, 2019; 15:1277–1282; doi: 10.2147/TCRM.S208185

118.

Jayne

, Scholefield

, Tolan

, et al.; FIAT Trial Collaborative Group. A multicenter randomized controlled trial comparing safety, efficacy, and cost-effectiveness of the surgisis anal fistula plug versus surgeon’s preference for transsphincteric fistula-in-ano: The FIAT trial. Ann Surg, 2021; 273(3):433–441; doi: 10.1097/SLA.0000000000003981

119.

Jamin

, Karam

, Marmouset

, et al. Tongue reconstruction after oncological resection: Analysis of the functional outcomes. J Stomatol Oral Maxillofac Surg, 2024; 125(3):101707; doi: 10.1016/j.jormas.2023.101707

120.

Sou

, Perng

, Ma

, et al. The Effect of Biological scaffold (biodesign) in postmastectomy direct-to-implant breast reconstruction: A 5-year single-institution experience. Ann Plast Surg, 2022; 88(Suppl 1):S92–S98; doi: 10.1097/SAP.0000000000003104

121.

Lai

, Yu

, Huang

, et al. Bone alteration and esthetics associated with implant-supported prostheses in the anterior maxilla under different implant placement timing: A retrospective clinical study of 1 to 3 years. J Prosthet Dent, 2024:S0022; doi: 10.1016/j.prosdent.2024.04.032

122.

Apaza Alccayhuaman

, Heimel

, Tangl

, et al. Active and passive mineralization of Bio-Gide((R)) membranes in rat calvaria defects. J Funct Biomater, 2024; 15(3):54; doi: 10.3390/jfb15030054

123.

, Xiang

, Liu

, et al. Combigraft versus Bio-Oss/Bio-Gide in alveolar ridge preservation: A prospective randomized controlled trial. Oral Surgery, 2022; 15(2):163–169.

124.

, Yuen

, Martin

, et al. A comparative study of a new porcine collagen membrane to bio-gide®. Science, Technology, Innovation, 2015:1–5.

125.

Kozlovsky

, Aboodi

, Moses

, et al. Bio-degradation of a resorbable collagen membrane (Bio-Gide) applied in a double-layer technique in rats. Clin Oral Implants Res, 2009; 20(10):1116–1123; doi: 10.1111/j.1600-0501.2009.01740.x

126.

Tawil

, Mawla

. Sinus floor elevation using a bovine bone mineral (Bio-Oss) with or without the concomitant use of a bilayered collagen barrier (Bio-Gide): A clinical report of immediate and delayed implant placement. Int J Oral Maxillofac Implants, 2001; 16(5):713–721.

127.

Palachur

, Prabhakara Rao

, Murthy

, et al. A comparative evaluation of bovine-derived xenograft (Bio-Oss Collagen) and type I collagen membrane (Bio-Gide) with bovine-derived xenograft (Bio-Oss Collagen) and fibrin fibronectin sealing system (TISSEEL) in the treatment of intrabony defects: A clinico-radiographic study. J Indian Soc Periodontol, 2014; 18(3):336–343; doi: 10.4103/0972-124X.134572

128.

Liang

, Wang

, Li

, et al. Evaluation of the effects of the small intestine submucosa biological membrane on guided bone regeneration and early loading of dental implants in the maxillary anterior region: A randomized controlled trial. J Prosthet Dent, 2025:S0022; doi: 10.1016/j.prosdent.2025.02.030

129.

Meijndert

, Raghoebar

, Meijndert

, et al. Single implants in the aesthetic region preceded by local ridge augmentation; a 10-year randomized controlled trial. Clin Oral Implants Res, 2017; 28(4):388–395; doi: 10.1111/clr.12811

130.

Meschi

, Vanhoenacker

, Strijbos

, et al. Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane. Clin Oral Investig, 2020; 24(12):4439–4453; doi: 10.1007/s00784-020-03309-1

131.

Djurkin

, Toma

, Brecx

, et al. Treatment of mandibular Class II furcations using bovine-derived bone xenograft with or without a collagen membrane: A randomized controlled trial. Quintessence Int, 2019; 50(8):652–660; doi: 10.3290/j.qi.a42957

132.

Tawil

, El-Ghoule

, Mawla

. Clinical evaluation of a bilayered collagen membrane (Bio-Gide) supported by autografts in the treatment of bone defects around implants. Int J Oral Maxillofac Implants, 2001; 16(6):857–863.

133.

Jung

, Sapata

, Hammerle

CHF

, et al. Combined use of xenogeneic bone substitute material covered with a native bilayer collagen membrane for alveolar ridge preservation: A randomized controlled clinical trial. Clin Oral Implants Res, 2018; 29(5):522–529; doi: 10.1111/clr.13149

134.

Scheyer

, Heard

, Janakievski

, et al. A randomized, controlled, multicentre clinical trial of post-extraction alveolar ridge preservation. J Clin Periodontol, 2016; 43(12):1188–1199; doi: 10.1111/jcpe.12623

135.

Araujo

, Lindhe

. Ridge preservation with the use of Bio-Oss collagen: A 6-month study in the dog. Clin Oral Implants Res, 2009; 20(5):433–440; doi: 10.1111/j.1600-0501.2009.01705.x

136.

Roccuzzo

, Gaudioso

, Bunino

, et al. Long-term stability of soft tissues following alveolar ridge preservation: 10-year results of a prospective study around nonsubmerged implants. Int J Periodontics Restorative Dent, 2014; 34(6):795–804; doi: 10.11607/prd.2133

137.

Keil

, Gollmer

, Zeidler-Rentzsch

, et al. Histological evaluation of extraction sites grafted with Bio-Oss Collagen: Randomized controlled trial. Ann Anat, 2021; 237:151722; doi: 10.1016/j.aanat.2021.151722

138.

Starch-Jensen

, Bruun

, Spin-Neto

. Endo-sinus bone gain following osteotome-mediated sinus floor elevation with Bio-Oss Collagen compared with no grafting material: A one-year single-blind randomized controlled trial. Int J Oral Maxillofac Surg, 2023; 52(11):1205–1215; doi: 10.1016/j.ijom.2023.03.009

139.

, Zhou

, Li

, et al. Comparison of the osteogenic effectiveness of an autogenous demineralised dentin matrix and Bio-Oss(R) in bone augmentation: A systematic review and meta-analysis. Br J Oral Maxillofac Surg, 2022; 60(7):868–876; doi: 10.1016/j.bjoms.2022.03.009

140.

Puvvada

, Chittamuru

, Raju

, et al. Efficacy of autologous cortico-cancellous bone graft and platelet-rich plasma with or without Bio-Oss in bone regeneration for unilateral alveolar cleft defects: A randomized controlled trial. J Stomatol Oral Maxillofac Surg, 2025:102256; doi: 10.1016/j.jormas.2025.102256

141.

Cordaro

, Bosshardt

, Palattella

, et al. Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: Histomorphometric results from a randomized controlled multicenter clinical trial. Clin Oral Implants Res, 2008; 19(8):796–803; doi: 10.1111/j.1600-0501.2008.01565.x

142.

Dang

, Peden

, Roy

, et al. Evaluation of CellerateRX Surgical Powder utility in reducing groin complications after femoral exposure. JVS-Vascular Insights, 2025; 3:100165; doi: 10.1016/j.jvsvi.2024.100165

143.

Kumar

, Banerjee

, Das

, et al. Hydrolyzed collagen powder dressing improves wound inflammation, perfusion, and breaking strength of repaired tissue. Adv Wound Care (New Rochelle), 2024; 13(2):70–82; doi: 10.1089/wound.2023.0065

144.

Nowrouzi

, Samir

. activated collagen powder significantly reduces surgical site infections in patients undergoing elective surgery. J Surg, 2023; 8; doi: 10.29011/2575-9760.001918

145.

Gitelman

. The use of sterile bovine Type 1 hydrolyzed collagen to support surgical wound management: A case series. JSM Neurosurgery and Spine, 2022; 9(1):1108; doi: 10.47739/2373-9479/1108

146.

Hotchkiss

. Retrospective study to evaluate the use of Type 1 bovine hydrolyzed collagen to support surgical wound healing after spinal surgery. JSM Neurosurgery and Spine, 2021; 8(1):1103.

147.

Evans

, Evans

. The effects of platelet-rich plasma and activated collagen on wound healing in primary total joint arthroplasty. Orthopedics, 2018; 41(2):e262–e267; doi: 10.3928/01477447-20180213-05

148.

Dickerman

, Reynolds

, Winters

. Operative closure technique utilizing bovine collagen fragments in a prospective analysis of 102 consecutive neurosurgery patients. JSM Neurosurgery and Spine, 2017; 5(2):1088.

149.

Hochstein

, Savage

. Examining the effectiveness of Type 1 activated hydrolyzed collagen in wound care. Today’s Wound Clinic, 2013.

150.

Hochstein

, Bhatia

. Collagen: Its role in wound healing. Podiatry Management, 2014:103–110.

151.

Newman

, Baratta

, Swartz

. Activated, type I collagen (CellerateRx) and its effectiveness in healing recalcitrant diabetic wounds: A case presentation. Adv Skin Wound Care, 2008; 21(8):370–374; doi: 10.1097/01.ASW.0000323535.51368.91

152.

Stafyla

, Dimakakos

, Koureas

, et al. Effect of collagen powder on lymphorrhea after modified radical mastectomy. A randomized controlled trial. Eur J Gynaecol Oncol, 2011; 32(2):185–187.

153.

Zelen

, Serena

, Denoziere

, et al. A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. Int Wound J, 2013; 10(5):502–507; doi: 10.1111/iwj.12097

154.

Zelen

, Serena

, Gould

, et al. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: A prospective, randomised, controlled, multi-centre comparative study examining clinical efficacy and cost. Int Wound J, 2016; 13(2):272–282; doi: 10.1111/iwj.12566

155.

Koob

, Rennert

, Zabek

, et al. Biological properties of dehydrated human amnion/chorion composite graft: Implications for chronic wound healing. Int Wound J, 2013; 10(5):493–500; doi: 10.1111/iwj.12140

156.

Bianchi

, Cazzell

, Vayser

, et al.; EpiFix VLU Study Group. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix((R))) allograft for the treatment of venous leg ulcers. Int Wound J, 2018; 15(1):114–122; doi: 10.1111/iwj.12843

157.

Chen

, Lopez

, Girard

, et al. Dehydrated human amnion/chorion membrane allografts for myelomeningocele and wound reconstruction. Childs Nerv Syst, 2021; 37(12):3721–3731; doi: 10.1007/s00381-021-05352-z

158.

Serena

, Carter

, Le

, et al.; EpiFix VLU Study Group. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen, 2014; 22(6):688–693; doi: 10.1111/wrr.12227

159.

Simman

, Abbas

. Foot wounds and the reconstructive ladder. Plast Reconstr Surg Glob Open, 2021; 9(12):e3989; doi: 10.1097/GOX.0000000000003989

160.

Thoma

, Gasser

TJW

, Hammerle

CHF

, et al. Soft tissue augmentation with a volume-stable collagen matrix or an autogenous connective tissue graft at implant sites: Five-year results of a randomized controlled trial post implant loading. J Periodontol, 2023; 94(2):230–243; doi: 10.1002/JPER.22-0226

161.

Posessor

, Vasilyev

, Badalyan

, et al. Gingival morphology after using Fibro-Gide and FibroMATRIX collagen matrices and connective tissue grafts around dental implants. Genes & Cells, 2024; 10(4):473–484; doi: 10.17816/gc634195

162.

Ibrahim

, Saymeh

. Alveolar ridge preservation with fibro-gide or connective tissue graft: A randomized controlled trial of soft and hard tissue changes. Clin Exp Dent Res, 2024; 10(4):e929; doi: 10.1002/cre2.929

163.

Harris

, Navya

, Rajasekar

. Efficacy of Fibro-Gide® in coronally advanced flap for the treatment of multiple gingival recession: A prospective clinical study. Jioh, 2024; 16(2):145–149.

164.

dos Santos

, Elias

, Lemos

, et al. In Vitro evaluation of two tissue substitutes for gingival augmentation. J Biomater Nanobiotechnol, 2023; 14(02):23–34.

165.

Tabanella

, Viale

. Porcine cross-linked collagen matrix for peri-implant vertical soft tissue augmentation: A randomized prospective observational study. J Funct Biomater, 2024; 15(9):261; doi: 10.3390/jfb15090261

166.

Billings

, Bow

, Newby

, et al. Effects on tissue integration of collagen scaffolds used for local delivery of gentamicin in a rat mandible defect model. Bioengineering (Basel), 2022; 9(7):275; doi: 10.3390/bioengineering9070275

167.

Tokpam

, Bains

, Chandra

, et al. Management of single tooth gingival recession using free gingival grafting followed by coronally advanced flap with cross-linked collagen matrix: A case report. AJOHAS, 2022; 12(7):7.

168.

Dadlani

, Joseph

, Anil

. Efficacy of xenogeneic collagen matrices in augmenting peri-implant soft tissue: A systematic review and meta-analysis. Clin Exp Dent Res, 2024; 10(4):e937; doi: 10.1002/cre2.937

169.

Mathes

, Wohlwend

, Uebersax

, et al. A bioreactor test system to mimic the biological and mechanical environment of oral soft tissues and to evaluate substitutes for connective tissue grafts. Biotechnol Bioeng, 2010; 107(6):1029–1039; doi: 10.1002/bit.22893

170.

Fingerhut

, Uranues

, Ettorre

, et al. European initial hands-on experience with HEMOPATCH, a novel sealing hemostatic patch: Application in general, gastrointestinal, biliopancreatic, cardiac, and urologic surgery. Surg Technol Int, 2014; 25:29–35.

171.

Lewis

, Kuntze

, Gulle

. Control of bleeding in surgical procedures: Critical appraisal of HEMOPATCH (Sealing Hemostat). Med Devices (Auckl), 2016; 9:1–10; doi: 10.2147/MDER.S90591

172.

Uranues

, Fingerhut

, Levin

, et al. Effectiveness of Hemopatch(R) versus Surgicel(R) Original to control mild and moderate liver bleeding. BMC Surg, 2022; 22(1):316; doi: 10.1186/s12893-022-01747-0

173.

Uranues

, Fingerhut

, Belyaev

, et al. Clinical impact of stump closure reinforced with hemopatch on the prevention of clinically relevant pancreatic fistula after distal pancreatectomy: A multicenter randomized trial. Ann Surg Open, 2021; 2(1):e033; doi: 10.1097/AS9.0000000000000033

174.

Teoh

, Liu

, Yuen

, et al. Hemopatch to prevent lymphatic leak after robotic prostatectomy and pelvic lymph node dissection: A randomized controlled trial. Cancers (Basel), 2022; 14(18):4476; doi: 10.3390/cancers14184476

175.

Montera

, Ficarola

, Plotti

, et al. The use of sealing hemostat patch (HEMOPATCH((R))) in laparotomic myomectomy: A prospective case-control study. Arch Gynecol Obstet, 2023; 307(5):1521–1528; doi: 10.1007/s00404-023-06957-2

176.

Schebesch

, Hrbac

, Jancalek

, et al. Real-world data on the usage of Hemopatch(R) as a hemostat and dural sealant in cranial and spinal neurosurgery. Cureus, 2023; 15(1):e34387; doi: 10.7759/cureus.34387

177.

Hupe

, Buttner

, Tabrizi

, et al. Hemopatch((R)) as a hemostatic agent is safe in partial nephrectomy: A large, single-surgeon retrospective evaluation. Adv Ther, 2021; 38(2):1024–1034; doi: 10.1007/s12325-020-01584-8

178.

Bubis

, Behman

, Roke

, et al.; HPB CONCEPT team. PATCH-DP: A single-arm phase II trial of intra-operative application of HEMOPATCH to the pancreatic stump to prevent post-operative pancreatic fistula following distal pancreatectomy. HPB (Oxford), 2022; 24(1):72–78; doi: 10.1016/j.hpb.2021.05.007

179.

Baumgartner

, Draxler

, Lewis

. Treatment of severe aortic bleeding using hemopatch in swine on dual antiplatelet therapy. J Invest Surg, 2016; 29(6):343–351; doi: 10.3109/08941939.2016.1154627

180.

Weltert

, D’Aleo

, Chirichilli

, et al. Prospective randomized clinical trial of HEMOPATCH topical sealant in cardiac surgery. Surg Technol Int, 2016;XXIX:sti29/756.

181.

Buch-Villa

, Castaner-Puga

, Delgado-Garcia

, et al. Polyethylene glycol-coated collagen patch (Hemopatchtm) versus axillary drainage. In patients undergoing axillary lymphadenectomy: Interim analysis of a multicentre, prospective, randomized and controlled study. Br J Cancer Res, 2022; 5(2):558–567.

182.

Lewis

, Ikeme

, Olubunmi

, et al. Clinical effectiveness and versatility of a sealing hemostatic patch (HEMOPATCH) in multiple surgical specialties. Expert Rev Med Devices, 2018; 15(5):367–376; doi: 10.1080/17434440.2018.1464909

183.

Ghanaati

, Schlee

, Webber

, et al. Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic. Biomed Mater, 2011; 6(1):015010; doi: 10.1088/1748-6041/6/1/015010

184.

Menceva

, Dimitrovski

, Popovska

, et al. Free gingival graft versus mucograft: Histological evaluation. Open Access Maced J Med Sci, 2018; 6(4):675–679; doi: 10.3889/oamjms.2018.127

185.

Schmitt

, Moest

, Lutz

, et al. Long-term outcomes after vestibuloplasty with a porcine collagen matrix (Mucograft((R))) versus the free gingival graft: A comparative prospective clinical trial. Clin Oral Implants Res, 2016; 27(11):e125–e133; doi: 10.1111/clr.12575

186.

Rokn

, Zare

, Haddadi

. Use of Mucograft Collagen Matrix((R)) versus free gingival graft to augment keratinized tissue around teeth: A randomized controlled clinical trial. Front Dent, 2020; 17(5):1–8; doi: 10.18502/fid.v17i1.3965

187.

Rotundo

, Pini-Prato

. Use of a new collagen matrix (mucograft) for the treatment of multiple gingival recessions: Case reports. Int J Periodontics Restorative Dent, 2012; 32(4):413–419.

188.

Al-Maawi

, Rother

, Halfter

, et al. Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft(R) enhances scaffold stability and reduces proinflammatory macrophage activation in vivo. Bioact Mater, 2022; 8:420–434; doi: 10.1016/j.bioactmat.2021.06.008

189.

Basudan

, Babay

, Ramalingam

, et al. Efficacy of Mucograft vs Conventional Resorbable collagen membranes in guided bone regeneration around standardized calvarial defects in rats: An in vivo microcomputed tomographic analysis. Int J Periodontics Restorative Dent, 2016; 36 Suppl:s109–s21; doi: 10.11607/prd.2261

190.

Vieira da

, Pagnoncelli

, Paes

, et al. The use of geistlich mucograft seal and geistlich bio-oss membranes in the post-exodontial alveolar sealing clinical case report. J Dental Health, Oral Disorders & Therapy, 2018; 2.

191.

Clementini

, Agostinelli

, Castelluzzo

, et al. The effect of immediate implant placement on alveolar ridge preservation compared to spontaneous healing after tooth extraction: Radiographic results of a randomized controlled clinical trial. J Clin Periodontol, 2019; 46(7):776–786; doi: 10.1111/jcpe.13125

192.

MacBeth

, Donos

, Mardas

. Alveolar ridge preservation with guided bone regeneration or socket seal technique. A randomised, single-blind controlled clinical trial. Clin Oral Implants Res, 2022; 33(7):681–699; doi: 10.1111/clr.13933

193.

Helio

, Daiane

, Elizabeth

, et al. Peri-implant soft tissue augmentation with palate subepitelial connective tissue graft compared to porcine collagen matrix: A randomized controlled clinical study and histomorphometric analysis. Int J Applied Dent Sci, 2019; 5(3):319–325.

194.

Farina

, Franceschetti

, Travaglini

, et al. Morbidity following transcrestal and lateral sinus floor elevation: A randomized trial. J Clin Periodontol, 2018; 45(9):1128–1139; doi: 10.1111/jcpe.12985

195.

Maiorana

, Pivetti

, Signorino

, et al. The efficacy of a porcine collagen matrix in keratinized tissue augmentation: A 5-year follow-up study. Int J Implant Dent, 2018; 4(1):1; doi: 10.1186/s40729-017-0113-3

196.

Rocchietta

, Schupbach

, Ghezzi

, et al. Soft tissue integration of a porcine collagen membrane: An experimental study in pigs. Int J Periodontics Restorative Dent, 2012; 32(1):e34–e40.

197.

Bergamo

ETP

, Balderrama

, Ferreira

, et al. Osteogenic differentiation and reconstruction of mandible defects using a novel resorbable membrane: An in vitro and in vivo experimental study. J Biomed Mater Res B Appl Biomater, 2023; 111(11):1966–1978; doi: 10.1002/jbm.b.35299

198.

Mostow

, Haraway

, Dalsing

, et al.; OASIS Venus Ulcer Study Group. Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: A randomized clinical trial. J Vasc Surg, 2005; 41(5):837–843; doi: 10.1016/j.jvs.2005.01.042

199.

Brown-Etris

, Milne

, Hodde

. An extracellular matrix graft (Oasis((R)) wound matrix) for treating full-thickness pressure ulcers: A randomized clinical trial. J Tissue Viability, 2019; 28(1):21–26; doi: 10.1016/j.jtv.2018.11.001

200.

Yeh

, Nazarian

, Demetri

, et al. Histopathological assessment of OASIS Ultra on critical-sized wound healing: A pilot study. J Cutan Pathol, 2017; 44(6):523–529; doi: 10.1111/cup.12925

201.

Rando

. Use of a biological extracellular matrix wound therapy to heal complex, chronic wounds. J Wound Care, 2009; 18(2):70–74; doi: 10.12968/jowc.2009.18.2.38746

202.

Hodde

, Badylak

, Brightman

, et al. Glycosaminoglycan content of small intestinal submucosa: A bioscaffold for tissue replacement. Tissue Eng, 1996; 2(3):209–217; doi: 10.1089/ten.1996.2.209

203.

Nihsen

, Zopf

, Ernst

, et al. Absorption of bioactive molecules into OASIS wound matrix. Adv Skin Wound Care, 2007; 20(10):541–548; doi: 10.1097/01.ASW.0000294756.97425.c9

204.

Kellar

, Diller

, Tabor

, et al. Improved wound closure rates and mechanical properties resembling native skin in murine diabetic wounds treated with a tropoelastin and collagen wound healing device. J Diabetes Clin Res, 2020; 2(3):86–99; doi: 10.33696/diabetes.1.024

205.

Heimbach

, Luterman

, Burke

, et al. Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg, 1988; 208(3):313–320; doi: 10.1097/00000658-198809000-00008

206.

Driver

, Lavery

, Reyzelman

, et al. A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair Regen, 2015; 23(6):891–900; doi: 10.1111/wrr.12357

207.

Branski

, Herndon

, Pereira

, et al. Longitudinal assessment of Integra in primary burn management: A randomized pediatric clinical trial. Crit Care Med, 2007; 35(11):2615–2623; doi: 10.1097/01.CCM.0000285991.36698.E2

208.

Lagus

, Sarlomo-Rikala

, Bohling

, et al. Prospective study on burns treated with Integra(R), a cellulose sponge and split thickness skin graft: Comparative clinical and histological study--randomized controlled trial. Burns, 2013; 39(8):1577–1587; doi: 10.1016/j.burns.2013.04.023

209.

Correa

, Castro

JCD

, Almeida

, et al. Evaluation of contraction of the split-thickness skin graft using three dermal matrices in the treatment of burn contractures: A randomised clinical trial. Wound Repair Regen, 2022; 30(2):222–231; doi: 10.1111/wrr.13002

210.

Almeida

, Gonqalves

, Correa

, et al. Evaluation of clinical and biomechanical features of scars resulting from the treatment of burn contractures comparing acellular dermal matrices: A randomized clinical trial. Ann Surg, 2023; 277(2):198–205; doi: 10.1097/SLA.0000000000005371

211.

Wang

, Mithieux

, Kong

, et al. Tropoelastin incorporation into a dermal regeneration template promotes wound angiogenesis. Adv Healthc Mater, 2015; 4(4):577–584; doi: 10.1002/adhm.201400571

212.

Shah

, Budania

, Shah

, et al. Unique way of chest wall reconstruction using Integra Dermal Regeneration Template (IDRT) in a patient with post traumatic mucormycosis: A case report. Int J Surg Case Rep, 2022; 95:107229; doi: 10.1016/j.ijscr.2022.107229

213.

Veves

, Sheehan

, Pham

. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg, 2002; 137(7):822–827; doi: 10.1001/archsurg.137.7.822

214.

Vin

, Teot

, Meaume

. The healing properties of Promogran in venous leg ulcers. J Wound Care, 2002; 11(9):335–341; doi: 10.12968/jowc.2002.11.9.26438

215.

Wollina

, Schmidt

, Kronert

, et al. Some effects of a topical collagen-based matrix on the microcirculation and wound healing in patients with chronic venous leg ulcers: Preliminary observations. Int J Low Extrem Wounds, 2005; 4(4):214–224; doi: 10.1177/1534734605283001

216.

Nisi

, Brandi

, Grimaldi

, et al. Use of a protease-modulating matrix in the treatment of pressure sores. Chir Ital, 2005; 57(4):465–468.

217.

Lobmann

, Ambrosch

, Schultz

, et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia, 2002; 45(7):1011–1016; doi: 10.1007/s00125-002-0868-8

218.

Kakagia

, Kazakos

, Xarchas

, et al. Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial. J Diabetes Complications, 2007; 21(6):387–391; doi: 10.1016/j.jdiacomp.2007.03.006

219.

Lazaro-Martinez

, Garcia-Morales

, Beneit-Montesinos

, et al. Randomized comparative trial of a collagen/oxidized regenerated cellulose dressing in the treatment of neuropathic diabetic foot ulcers. Cir Esp, 2007; 82(1):27–31; doi: 10.1016/s0009-739x(07)71657-3

220.

Chen

, Sivaraj

, Davitt

, et al. Pullulan-Collagen hydrogel wound dressing promotes dermal remodelling and wound healing compared to commercially available collagen dressings. Wound Repair Regen, 2022; 30(3):397–408; doi: 10.1111/wrr.13012

221.

Karr

, Taddei

, Picchietti

, et al. A morphological and biochemical analysis comparative study of the collagen products Biopad, Promogram, Puracol, and Colactive. Adv Skin Wound Care, 2011; 24(5):208–216; doi: 10.1097/01.ASW.0000397897.18003.ce

222.

Cullen

, Smith

, McCulloch

, et al. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen, 2002; 10(1):16–25; doi: 10.1046/j.1524-475x.2002.10703.x

223.

Armstrong

, Hanft

, Driver

, et al.; Diabetic Foot Nutrition Study Group. Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: A prospective randomized controlled trial. Diabet Med, 2014; 31(9):1069–1077; doi: 10.1111/dme.12509

224.

Narang

, Narang

, et al. Management of bronchopleural fistula with the nutritional supplement-juven, Vitamins A, and C, Zinc Gluconate, and Folic Acid. Chest Journal, 2016; 150(4):567A.

225.

Berk

, James

, Schwartz

, et al.; RTOG. A randomized, double-blind, placebo-controlled trial of a beta-hydroxyl beta-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122). Support Care Cancer, 2008; 16(10):1179–1188; doi: 10.1007/s00520-008-0403-7

226.

Kuhls

, Rathmacher

, Musngi

, et al. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients. J Trauma, 2007; 62(1):125–131; discussion 131-2; doi: 10.1097/TA.0b013e31802dca93

227.

Setliff

, Russell

, Wawrose

, et al. Focused nutritional supplementation reduces wound complications in patients undergoing spinal fusion. The Spine Journal, 2023; 23(9):S137.

228.

Moore

, Dobson

, Castelllino

, et al. Phase angle, an alternative physiological tool to assess wound treatment in chronic nonhealing wounds. J Am Col Certif Wound Spec, 2011; 3(1):2–7; doi: 10.1016/j.jcws.2011.06.001

229.

Williams

, Abumrad

, Barbul

. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg, 2002; 236(3):369–374; discussion 374-5; doi: 10.1097/00000658-200209000-00013

230.

Hicks-Roof

. The use of an arginine-enriched oral nutrition supplement to enhance wound healing from a Cesarean section. Case Rep Clin Nutr, 2018; 1(1–3):1–7.

231.

Anz

, Jordan

, Ostrander

3rd , et al. Augmentation of ACL autograft reconstruction with an amnion collagen matrix wrap and bone marrow aspirate concentrate: A pilot randomized controlled trial with 2-year follow-up. Orthop J Sports Med, 2023; 11(11):23259671231210035; doi: 10.1177/23259671231210035

232.

GnanaDev

, Malkoc

, Jeney

, et al. A multicenter analysis of revision of aneurysmal dialysis access using bovine carotid artery conduit. Ann Vasc Surg, 2023; 97:399–404; doi: 10.1016/j.avsg.2023.05.030

233.

Dyer-Kindy

, Heelan Gladden

, Gralla

, et al. Relationship between bovine carotid artery grafts for hemodialysis access and human leukocyte antigen sensitization. Hemodial Int, 2020; 24(1):36–42; doi: 10.1111/hdi.12784

234.

Lindsey

, Echeverria

, Cheung

, et al. Lower extremity bypass using bovine carotid artery graft (artegraft): An analysis of 124 cases with long-term results. World J Surg, 2018; 42(1):295–301; doi: 10.1007/s00268-017-4161-x

235.

Abdoli

, Mahajan

, Han

, et al. Early cannulation of bovine carotid artery grafts (Artegraft) after primary vascular access and fistula revision procedures. J Vasc Surg, 2018; 68(6):1865–1871; doi: 10.1016/j.jvs.2018.04.061

236.

Fang

, Ellman

, Andersen

. Review: Tissue engineering of small-diameter vascular grafts and their in vivo evaluation in large animals and humans. Cells, 2021; 10(3):713; doi: 10.3390/cells10030713

237.

Linke

, Ulmer

, Imhoff

. Replacement of the meniscus with a collagen implant (CMI). Oper Orthop Traumatol, 2006; 18(5–6):453–462; doi: 10.1007/s00064-006-1188-9

238.

Duarte-Silva

, Guerra-Pinto

, Camelo-Barbosa

, et al. Integration and vascular ingrowth of a collagen meniscal implant: A case report. Malays Orthop J, 2019; 13(2):38–41; doi: 10.5704/MOJ.1907.007

239.

Hagmeijer

, Vonk

, Kouwenhoven

, et al. Surgical feasibility of a one-stage cell-based arthroscopic procedure for meniscus regeneration: A cadaveric study. Tissue Eng Part C Methods, 2018; 24(12):688–696; doi: 10.1089/ten.TEC.2018.0240

240.

Winkler

, Rothrauff

, Buerba

, et al. Meniscal substitution, a developing and long-awaited demand. J Exp Orthop, 2020; 7(1):55; doi: 10.1186/s40634-020-00270-6

241.

Dahmardehei

, Moin Ara

, Akbari Ahmadabadi

. Comparison of the effect of using collective plus ag dressing and vaseline gauze dressing in the donor of split-thickness burn grafts. World J Plast Surg, 2023; 12(3):57–63; doi: 10.61186/wjps.12.3.57

242.

Salehi

, Momeni

, Ebrahimi

, et al. Comparing the effect of colactive plus ag dressing versus nitrofurazone and vaseline gauze dressing in the treatment of second-degree burns. Ann Burns Fire Disasters, 2018; 31(3):204–208.

243.

Farhani

, Forooshani

, Roshanbin

, et al. Treatment of traumatic wounds with new dressings in an patient: A case report. Journal of Modern Family Medicine, 2021; 1(E101).

244.

Alavi

, Archer

, Coutts

. Use of an advanced collagen matrix dressing on patients with complex chronic lower extremity ulcers: A case series. SAGE Open Med Case Rep, 2021; 9:2050313X211013684; doi: 10.1177/2050313X211013684

245.

Tajalli

, Hamzekhani

, Farzi

, et al. Successful topical treatment of a gunshot wound: A case report. Trauma Case Rep, 2023; 44:100787; doi: 10.1016/j.tcr.2023.100787

246.

Pandey

, Kumar

. Single visit apexification in a replanted tooth with CollaCote And MTA - A case report. Int J Res Health and Allied Sciences, 2016; 2(1).

247.

Sharma

, Kumar

, Puri

, et al. Application of platelet-rich fibrin membrane and collagen dressing as palatal bandage for wound healing: A randomized clinical control trial. Indian J Dent Res, 2019; 30(6):881–888; doi: 10.4103/ijdr.IJDR_370_17

248.

Moustafa

, Omar

, Osman

, et al. Effect of CollaTape collagen wound dressing alone and combined with ingenios synthetic bone graft on the socket healing in rabbits. Alexandria Dental Journal, 2015; 40(1):27–32; doi: 10.21608/adjalexu.2015.58731

249.

Johnson

, Britto

, Guelmann

. Impact of a biological barrier in pulpectomies of primary molars. Pediatr Dent, 2006; 28(6):506–510.

250.

, Baumgartner

, Marshall

. Cardiovascular effects and efficacy of a hemostatic agent in periradicular surgery. J Endod, 2004; 30(6):379–383; doi: 10.1097/00004770-200406000-00001

251.

Ahn

, Lee

, Ji

, et al. Decellularized human adipose tissue as an alternative graft material for bone regeneration. Tissue Eng Regen Med, 2022; 19(5):1089–1098; doi: 10.1007/s13770-022-00451-7

252.

Ansari

, Ahmed

, Abdulaziz

, et al. Wound healing of cyanoacrylate vs collagen among patients undergoing oral surgery; a systematic review. Ann Dent Spec, 2023; 11(4):56–61.

253.

Cornell

, Lane

, Chapman

, et al. Multicenter trial of Collagraft as bone graft substitute. J Orthop Trauma, 1991; 5(1):1–8.

254.

Hagen

, Gorenoi

, Schonermark

. Bone graft substitutes for the treatment of traumatic fractures of the extremities. GMS Health Technol Assess, 2012; 8:Doc04; doi: 10.3205/hta000102

255.

Walsh

, Harrison

, Loefler

, et al. Mechanical and histologic evaluation of Collagraft in an ovine lumbar fusion model. Clin Orthop Relat Res, 2000; 375(375):258–266; doi: 10.1097/00003086-200006000-00031

256.

Chapman

, Bucholz

, Cornell

. Treatment of acute fractures with a collagen-calcium phosphate graft material. A randomized clinical trial. J Bone Joint Surg Am, 1997; 79(4):495–502; doi: 10.2106/00004623-199704000-00004

257.

Eyckmans

, Roberts

, Schrooten

, et al. A clinically relevant model of osteoinduction: A process requiring calcium phosphate and BMP/Wnt signalling. J Cell Mol Med, 2010; 14(6B):1845–1856; doi: 10.1111/j.1582-4934.2009.00807.x

258.

Bansal

, Chauhan

, Sharma

, et al. Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute for posterolateral spinal fusion. Indian J Orthop, 2009; 43(3):234–239; doi: 10.4103/0019-5413.49387

259.

DeLustro

, Dasch

, Keefe

, et al. Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. Clin Orthop Relat Res, 1990; 260(260):263–279.

260.

Salvatore

, Natali

, Brunetti

, et al. An update on the clinical efficacy and safety of collagen injectables for aesthetic and regenerative medicine applications. Polymers (Basel), 2023; 15(4):1020; doi: 10.3390/polym15041020

261.

Dhinsa

, Bowman

, Morar

, et al. The use of collagen injections in the treatment of metatarsalgia: A case report. J Foot Ankle Surg, 2010; 49(6):565.e5–565.e7; doi: 10.1053/j.jfas.2010.07.013

262.

Mathison

, Villari

, Klein

, et al. Comparison of outcomes and complications between awake and asleep injection laryngoplasty: A case-control study. Laryngoscope, 2009; 119(7):1417–1423; doi: 10.1002/lary.20485

263.

Narins

, Baumann

, Brandt

, et al. A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles. J Am Acad Dermatol, 2010; 62(3):448–462; doi: 10.1016/j.jaad.2009.07.040

264.

Thioly-Bensoussan

. Non-hyaluronic acid fillers. Clin Dermatol, 2008; 26(2):160–176; doi: 10.1016/j.clindermatol.2007.09.017

265.

Man

, Rao

, Goldman

. A double-blind, comparative study of nonanimal-stabilized hyaluronic acid versus human collagen for tissue augmentation of the dorsal hands. Dermatol Surg, 2008; 34(8):1026–1031; doi: 10.1111/j.1524-4725.2008.34201.x

266.

England

, Tan

, Shumaker

, et al. Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model. Lasers Surg Med, 2005; 37(5):356–365; doi: 10.1002/lsm.20253

267.

Shumaker

, England

, Dover

, et al. Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: Part 2. Lasers Surg Med, 2006; 38(3):211–217; doi: 10.1002/lsm.20292

268.

Chen

, Tzeng

, Wang

. Treatment of severe burn with DermACELL((R)), an acellular dermal matrix. Int J Burns Trauma, 2012; 2(2):105–109.

269.

Vashi

. Clinical outcomes for breast cancer patients undergoing mastectomy and reconstruction with use of DermACELL, a sterile, room temperature acellular dermal matrix. Plast Surg Int, 2014; 2014:704323; doi: 10.1155/2014/704323

270.

Jeon

, Ha

, Jin

. Direct comparison of CGCRYODERM and DermACELL in the same patient for outcomes in bilateral implant-based breast reconstruction: A retrospective case series. Gland Surg, 2021; 10(7):2113–2122; doi: 10.21037/gs-21-149

271.

Bullocks

. DermACELL: A novel and biocompatible acellular dermal matrix in tissue expander and implant-based breast reconstruction. Eur J Plast Surg, 2014; 37(10):529–538; doi: 10.1007/s00238-014-0995-8

272.

Marston

, Hanft

, Norwood

, et al.; Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: Results of a prospective randomized trial. Diabetes Care, 2003; 26(6):1701–1705; doi: 10.2337/diacare.26.6.1701

273.

Marston

. Dermagraft, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer. Expert Rev Med Devices, 2004; 1(1):21–31; doi: 10.1586/17434440.1.1.21

274.

Sibbald

, Zuker

, Coutts

, et al. Using a dermal skin substitute in the treatment of chronic wounds secondary to recessive dystrophic epidermolysis bullosa: A case series. Ostomy Wound Manage, 2005; 51(11):22–46.

275.

Joncas

, Prado

, Price Ritchie

, et al. The closure of a large chronic abdominal wound in a neonate utilizing a biologic dressing. Adv Skin Wound Care, 2010; 23(9):404–405; doi: 10.1097/01.ASW.0000383212.95911.f5

276.

Naughton

, Mansbridge

, Gentzkow

. A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. Artif Organs, 1997; 21(11):1203–1210; doi: 10.1111/j.1525-1594.1997.tb00476.x

277.

Hansbrough

, Dore

, Hansbrough

. Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin grafts on excised burn wounds. J Burn Care Rehabil, 1992; 13(5):519–529; doi: 10.1097/00004630-199209000-00004

278.

Hansbrough

, Morgan

, Greenleaf

, et al. Composite grafts of human keratinocytes grown on a polyglactin mesh-cultured fibroblast dermal substitute function as a bilayer skin replacement in full-thickness wounds on athymic mice. J Burn Care Rehabil, 1993; 14(5):485–494; doi: 10.1097/00004630-199309000-00001

279.

Narins

, Brandt

, Lorenc

, et al. A randomized, multicenter study of the safety and efficacy of Dermicol-P35 and non-animal-stabilized hyaluronic acid gel for the correction of nasolabial folds. Dermatol Surg, 2007; 33 Suppl 2:S213–S221; discussion S221; doi: 10.1111/j.1524-4725.2007.33364.x

280.

Shoshani

, Markovitz

, Cohen

, et al. Skin test hypersensitivity study of a cross-linked, porcine collagen implant for aesthetic surgery. Dermatol Surg, 2007; 33 Suppl 2:S152–S8; doi: 10.1111/j.1524-4725.2007.33355.x

281.

Braun

, Braun

. Nodule formation following lip augmentation using porcine collagen-derived filler. J Drugs Dermatol, 2008; 7(6):579–581.

282.

Pitaru

, Noff

, Blok

, et al. Long-term efficacy of a novel ribose-cross-linked collagen dermal filler: A histologic and histomorphometric study in an animal model. Dermatol Surg, 2007; 33(9):1045–1054; discussion 1054; doi: 10.1111/j.1524-4725.2007.33218.x

283.

Armstrong

, Orgill

, Galiano

, et al. A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial. Int Wound J, 2024; 21(4):e14882; doi: 10.1111/iwj.14882

284.

Millan

, Da Silva

, Coltro

, et al. Wound management of partial-thickness skingraft donor areas with a collagen and alginate dressing (Fibracol®): Findings in 35 patients. Rev Bras Cir Plast, 2015; 30(2); doi: 10.5935/2177-1235.2015RBCP0148

285.

Sharma

, Dheer

, Puri

, et al. Insights of biopolymeric blended formulations for diabetic wound healing. Int J Pharm, 2024; 656:124099; doi: 10.1016/j.ijpharm.2024.124099

286.

Shi

, Ermis

, Kiedaisch

, et al. The effect of various wound dressings on the activity of debriding enzymes. Adv Skin Wound Care, 2010; 23(10):456–462; doi: 10.1097/01.ASW.0000383224.64524.ae

287.

Tavelli

, Barootchi

, Rodriguez

, et al. Living cellular constructs for keratinized tissue augmentation: A 13-year follow-up from a split-mouth randomized, controlled, clinical trial. J Periodontol, 2023; 94(11):1302–1314; doi: 10.1002/JPER.23-0040

288.

McGuire

, Scheyer

, Nunn

, et al. A pilot study to evaluate a tissue-engineered bilayered cell therapy as an alternative to tissue from the palate. J Periodontol, 2008; 79(10):1847–1856; doi: 10.1902/jop.2008.080017

289.

Lopez-Navas

, Torrents

, Sanchez-Pernaute

, et al. Compliance in non-clinical development of cell-, gene-, and tissue-based medicines: Good practice for better therapies. Stem Cells Transl Med, 2022; 11(8):805–813; doi: 10.1093/stcltm/szac046

290.

Lavery

, Fulmer

, Shebetka

, et al.; Grafix Diabetic Foot Ulcer Study Group. The efficacy and safety of Grafix((R)) for the treatment of chronic diabetic foot ulcers: Results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J, 2014; 11(5):554–560; doi: 10.1111/iwj.12329

291.

Lavery

, Fulmer

, Shebetka

, et al. Open-label extension phase of a chronic diabetic foot ulcer multicenter, controlled, randomized clinical trial using cryopreserved placental membrane. Wounds, 2018; 30(9):283–289.

292.

Fang

, Vangsness

CT.

Jr ., Orthobiologic products: Preservation options for orthopedic research and clinical applications. J Clin Med, 2024; 13(21):6577; doi: 10.3390/jcm13216577

293.

Regulski

, Jacobstein

, Petranto

, et al. A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds. Ostomy Wound Manage, 2013; 59(12):38–43.

294.

Gibbons

. Grafix((R)), a cryopreserved placental membrane, for the treatment of chronic/stalled wounds. Adv Wound Care (New Rochelle), 2015; 4(9):534–544; doi: 10.1089/wound.2015.0647

295.

Farivar

, Toursavadkohi

, Monahan

, et al. Prospective study of cryopreserved placental tissue wound matrix in the management of chronic venous leg ulcers. J Vasc Surg Venous Lymphat Disord, 2019; 7(2):228–233; doi: 10.1016/j.jvsv.2018.09.016

296.

Adams

, Zobitz

, Reach

Jr , et al. Rotator cuff repair using an acellular dermal matrix graft: An in vivo study in a canine model. Arthroscopy, 2006; 22(7):700–709; doi: 10.1016/j.arthro.2006.03.016

297.

Barber

, Burns

, Deutsch

, et al. A prospective, randomized evaluation of acellular human dermal matrix augmentation for arthroscopic rotator cuff repair. Arthroscopy, 2012; 28(1):8–15; doi: 10.1016/j.arthro.2011.06.038

298.

Sharma

, El Refaiy

, Sibly

. Short-term results of rotator cuff repair using GraftJacket as an interpositional tissue-matched thickness graft. J Orthop, 2018; 15(2):732–735; doi: 10.1016/j.jor.2018.05.037

299.

Bond

, Dopirak

, Higgins

, et al. Arthroscopic replacement of massive, irreparable rotator cuff tears using a GraftJacket allograft: technique and preliminary results. Arthroscopy, 2008; 24(4):403–409 e1; doi: 10.1016/j.arthro.2007.07.033

300.

Boeckstyns

, Sorensen

, Vineta

, et al. Collagen conduit versus microsurgical neurorrhaphy: 2-year follow-up of a prospective, blinded clinical and electrophysiological multicenter randomized, controlled trial. J Hand Surg Am, 2013; 38(12):2405–2411; doi: 10.1016/j.jhsa.2013.09.038

301.

Bedar

, van Wijnen

, Shin

. Safety of allogeneic mesenchymal stem cell seeding of NeuraGen nerve guides in a Rabbit model. Tissue Eng Part C Methods, 2023; 29(2):43–53; doi: 10.1089/ten.TEC.2022.0159

302.

Pinzon-Herrera

, Magness

, Apodaca-Reyes

, et al. Surface modification of nerve guide conduits with ECM coatings and investigating their impact on schwann cell response. Adv Healthc Mater, 2024; 13(14):e2304103; doi: 10.1002/adhm.202304103

303.

Rbia

, Bulstra

, Saffari

, et al. Collagen nerve conduits and processed nerve allografts for the reconstruction of digital nerve gaps: A single-institution case series and review of the literature. World Neurosurg, 2019; 127:e1176–e1184; doi: 10.1016/j.wneu.2019.04.087

304.

Wilson

, Chuang

, Ziccardi

. Lingual nerve microsurgery outcomes using 2 different conduits: A retrospective cohort study. J Oral Maxillofac Surg, 2017; 75(3):609–615; doi: 10.1016/j.joms.2016.09.022

305.

McQuilling

, Kammer

, Kimmerling

, et al. Characterisation of dehydrated amnion chorion membranes and evaluation of fibroblast and keratinocyte responses in vitro. Int Wound J, 2019; 16(3):827–840; doi: 10.1111/iwj.13103

306.

Cazzell

, Caporusso

, Vayser

, et al. Dehydrated amnion chorion membrane versus standard of care for diabetic foot ulcers: A randomised controlled trial. J Wound Care, 2024; 33(Sup7):S4–S14; doi: 10.12968/jowc.2024.0139

307.

Moore

, Van De Walle

, Chang

, et al. Human perinatal-derived biomaterials. Adv Healthc Mater, 2017; 6(18); doi: 10.1002/adhm.201700345

308.

Koenig

, Burns

, Hayes

. Necrotic granulomatous inflammation after use of small intestine submucosa matrix for recurrent compression neuropathy. Plast Reconstr Surg Glob Open, 2022; 10(6):e4378; doi: 10.1097/GOX.0000000000004378

309.

McQuilling

, Sanders

, Poland

, et al. Dehydrated amnion/chorion improves achilles tendon repair in a diabetic animal model. Wounds, 2019; 31(1):19–25.

310.

Rydningen

, Dehli

, Wilsgaard

, et al. Sacral neuromodulation compared with injection of bulking agents for faecal incontinence following obstetric anal sphincter injury—a randomized controlled trial. Colorectal Dis, 2017; 19(5):O134–O144; doi: 10.1111/codi.13632

311.

Cheng

, Abbas

, Tejirian

. Outcome of abdominal wall hernia repair with biologic mesh: Permacol versus Strattice. Am Surg, 2014; 80(10):999–1002.

312.

Chand

, Indeck

, Needleman

, et al. A retrospective study evaluating the use of Permacol surgical implant in incisional and ventral hernia repair. Int J Surg, 2014; 12(4):296–303; doi: 10.1016/j.ijsu.2014.01.025

313.

Gaertner

, Bonsack

, Delaney

. Experimental evaluation of four biologic prostheses for ventral hernia repair. J Gastrointest Surg, 2007; 11(10):1275–1285; doi: 10.1007/s11605-007-0242-8

314.

Parker

, Armstrong

, Frizzi

, et al. Porcine dermal collagen (Permacol) for abdominal wall reconstruction. Curr Surg, 2006; 63(4):255–258; doi: 10.1016/j.cursur.2006.05.003

315.

MacLeod

, Cambrey

, Williams

, et al. Evaluation of Permacol as a cultured skin equivalent. Burns, 2008; 34(8):1169–1175; doi: 10.1016/j.burns.2008.01.013

316.

MacLeod

, Williams

, Sanders

, et al. Prefabricated skin flaps in a rat model based on a dermal replacement matrix Permacol. Br J Plast Surg, 2003; 56(8):775–783; doi: 10.1016/s0007-1226(03)00383-7

317.

Simon

, Johnson

, Naig

, et al. Permacol interposition graft as an alternative to vein in contaminated wounds using a rabbit model. Ann Vasc Surg, 2015; 29(6):1307–1314; doi: 10.1016/j.avsg.2015.05.001

318.

McGrath

, Hardy

, McNab

. Efficacy of porcine acellular dermal matrix in the management of lower eyelid retraction: Case series and review of the literature. Graefes Arch Clin Exp Ophthalmol, 2020; 258(9):1999–2006; doi: 10.1007/s00417-020-04660-5

319.

Hunter

. Cartilage sparing septal perforation repair using rotation flaps and a collagen interposition graft: A case series. Ann Otol Rhinol Laryngol, 2021; 130(7):745–751; doi: 10.1177/0003489420970592

320.

Cornwell

, Landsman

, James

. Extracellular matrix biomaterials for soft tissue repair. Clin Podiatr Med Surg, 2009; 26(4):507–523; doi: 10.1016/j.cpm.2009.08.001

321.

Rennert

, Sorkin

, Garg

, et al. Cellular response to a novel fetal acellular collagen matrix: Implications for tissue regeneration. Int J Biomater, 2013; 2013:527957; doi: 10.1155/2013/527957

322.

Lullove

. Acellular fetal bovine dermal matrix in the treatment of nonhealing wounds in patients with complex comorbidities. J Am Podiatr Med Assoc, 2012; 102(3):233–239; doi: 10.7547/1020233

323.

Neill

, Lineaweaver

. Tissue response to bovine fetal collagen extracellular matrix in full-thickness skin wounds. Am J Clin Pathol, 2013; 140(2):248–252; doi: 10.1309/AJCPMF3B9XJAKXKM

324.

Neill

, James

, Lineaweaver

. Utilizing biologic assimilation of bovine fetal collagen in staged skin grafting. Ann Plast Surg, 2012; 68(5):451–456; doi: 10.1097/SAP.0b013e31824189ed

325.

Kavros

. Acellular fetal bovine dermal matrix for treatment of chronic ulcerations of the midfoot associated with Charcot neuroarthropathy. Foot Ankle Spec, 2012; 5(4):230–234; doi: 10.1177/1938640012449037

326.

Karr

. Retrospective comparison of diabetic foot ulcer and venous stasis ulcer healing outcome between a dermal repair scaffold (PriMatrix) and a bilayered living cell therapy (Apligraf). Adv Skin Wound Care, 2011; 24(3):119–125; doi: 10.1097/01.ASW.0000395038.28398.88

327.

Hayn

. Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix. Int Wound J, 2014; 11(6):675–680; doi: 10.1111/iwj.12028

328.

Kavros

, Dutra

, Gonzalez-Cruz

, et al. The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: A prospective multicenter study. Adv Skin Wound Care, 2014; 27(8):356–362; doi: 10.1097/01.ASW.0000451891.87020.69

329.

Strauss

, Brietstein

. Fetal Bovine dermal repair scaffold used for the treatment of difficult-to-heal complex wounds. Wounds, 2012; 24(11):327–334.

330.

Gottrup

, Cullen

, Karlsmark

, et al. Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment. Wound Repair Regen, 2013; 21(2):216–225; doi: 10.1111/wrr.12020

331.

Loh

, Goh

BKL

, Kong

, et al. Combination therapy of oxidised regenerated cellulose/collagen/silver dressings with negative pressure wound therapy for coverage of exposed critical structures in complex lower-extremity wounds. Int Wound J, 2020; 17(5):1356–1365; doi: 10.1111/iwj.13406

332.

Chowdhry

. Use of Oxidized Regenerated Cellulose (ORC)/collagen/silver-ORC dressings to help manage skin graft donor site wounds. JPRAS Open, 2019; 22:33–40; doi: 10.1016/j.jpra.2019.08.001

333.

Fletcher

, Dhoonmoon

, Chadwick

, et al. Use of Oxidised Regenerated Cellulose (ORC) and collagen dressings (PROMOGRAN™ Protease Modulating Matrix and PROMOGRAN PRISMA™ Wound Balancing Matrix) to kick-start the treatment of chronic wounds. The Diabetic Foot Journal, 2020; 23(1):62–9.

334.

Bourdillon

, Delury

, Cullen

. Biofilms and delayed healing - an in vitro evaluation of silver- and iodine-containing dressings and their effect on bacterial and human cells. Int Wound J, 2017; 14(6):1066–1075; doi: 10.1111/iwj.12761

335.

Vos

, Nakauchi

, Capanu

, et al. Phase II Trial evaluating esophageal anastomotic reinforcement with a biologic, degradable, extracellular matrix after total gastrectomy and esophagectomy. J Am Coll Surg, 2022; 234(5):910–917; doi: 10.1097/XCS.0000000000000113

336.

Capella-Monsonis

, De Pieri

, Peixoto

, et al. Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: A comparative study between a collagen scaffold and two xenografts. Stem Cell Res Ther, 2020; 11(1):510; doi: 10.1186/s13287-020-02021-x

337.

Kim

, Kaminsky

, Summitt

, et al. New innovations for deep partial-thickness burn treatment with ACell MatriStem matrix. Adv Wound Care (New Rochelle), 2016; 5(12):546–552; doi: 10.1089/wound.2015.0681

338.

Huen

, Macaraeg

, Davis-Dao

, et al. Single-layer acellular porcine bladder matrix as graft in corporoplasty for ventral curvature in pediatric proximal hypospadias repair: An initial experience. Urology, 2022; 169:196–201; doi: 10.1016/j.urology.2022.07.025

339.

Frykberg

, Cazzell

, Arroyo-Rivera

, et al. Evaluation of tissue engineering products for the management of neuropathic diabetic foot ulcers: An interim analysis. J Wound Care, 2016; 25(Sup7):S18–S25; doi: 10.12968/jowc.2016.25.Sup7.S18

340.

Liang

, Knight

, Barone

, et al. Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque. Am J Obstet Gynecol, 2017; 216(2):153e1–153e9; doi: 10.1016/j.ajog.2016.09.073

341.

Abdelaziz

, Shaaban

, Abdelhalim

, et al. Effect of CollaPlug on the healing of extraction sockets in patients under oral anticoagulant therapy (clinical study). Alexandria Dental Journal, 2015; 40(2):166–172; doi: 10.21608/adjalexu.2015.58743

342.

Ahmed

, Gopalakrishna

, Shetty

, et al. Efficacy of PRF vs PRF + Biodegradable collagen plug in post-extraction preservation of socket. J Contemp Dent Pract, 2019; 20(11):1323–1328.

343.

Singh

, Madhan

. Comparison of ability of platelet-rich Fibrin vs CollaPlug in maintaining the buccal bone height of sockets following extractions in 20 patients. Journal of Health Sciences & Research, 2017; 8(1):1–6.

344.

Gupta

, Chaudhary

, Khurana

, et al. Preservation of soft tissue architecture in anterior maxillary region using Colla-Plug in conjunction with immediate implant placement – a case report. Journal of Prosthodontics Dentistry, 2022; 17(1):1–5.

345.

Zou

, Liu

, Yin

, et al. In vitro evaluation of the sealing ability of MTA used for the repair of furcation perforations with and without the use of an internal matrix. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2008; 105(6):e61–e65; doi: 10.1016/j.tripleo.2008.01.038

346.

Lammens

, Marechal

, Delport

, et al. A cell-based combination product for the repair of large bone defects. Bone, 2020; 138:115511; doi: 10.1016/j.bone.2020.115511

347.

Hendrich

, Franz

, Waertel

, et al. Safety of autologous bone marrow aspiration concentrate transplantation: Initial experiences in 101 patients. Orthop Rev (Pavia), 2009; 1(2):e32; doi: 10.4081/or.2009.e32

348.

Kerckhofs

, Chai

, Luyten

, et al. Combining microCT-based characterization with empirical modelling as a robust screening approach for the design of optimized CaP-containing scaffolds for progenitor cell-mediated bone formation. Acta Biomater, 2016; 35:330–340; doi: 10.1016/j.actbio.2016.02.037

349.

, Kerckhofs

, Geeroms

, et al. Deciphering the combined effect of bone morphogenetic protein 6 and calcium phosphate on bone formation capacity of periosteum derived cells-based tissue engineering constructs. Acta Biomater, 2018; 80:97–107; doi: 10.1016/j.actbio.2018.09.046

350.

Verdolino

, Thomason

, Fotticchia

, et al. Wound dressings: Curbing inflammation in chronic wound healing. Emerg Top Life Sci, 2021; 5(4):523–537; doi: 10.1042/ETLS20200346

351.

Bosque

, Frampton

, Chaffin

, et al. Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers. Int Wound J, 2022; 19(4):741–753; doi: 10.1111/iwj.13670

352.

Sabo

, Le

, Yaakov

, et al. A post-marketing surveillance study of chronic wounds treated with a native collagen calcium alginate dressing. Owm, 2018; 64(4):38–43.

353.

Ranganathan

, Balaji

, Krishnaraj

, et al. Assessment of regeneration of bone in the extracted third molar sockets augmented using xenograft (CollaPlug(TN) Zimmer) in comparison with the normal healing on the contralateral side. J Pharm Bioallied Sci, 2017; 9(Suppl 1):S180–S186; doi: 10.4103/jpbs.JPBS_176_17

354.

Porto

, Stolpe

, Badaoui

, et al. One-year clinical outcomes following Edwards INSPIRIS RESILIA aortic valve implantation in 487 young patients with severe aortic stenosis: A single-center experience. Front Cardiovasc Med, 2023; 10:1196447; doi: 10.3389/fcvm.2023.1196447

355.

Shala

, Niclauss

. Early results of the Resilia Inspiris aortic valve in the old age patients - a retrospective comparison with the Carpentier Edwards Magna Ease. J Cardiovasc Thorac Res, 2020; 12(3):222–226; doi: 10.34172/jcvtr.2020.38

356.

Bernard

, Georges

, Hecht

, et al. Mid-term clinical and echocardiographic results of the INSPIRIS RESILIA aortic valve: A retrospective comparison to the Magna Ease. Interdiscip Cardiovasc Thorac Surg, 2023; 37(1); doi: 10.1093/icvts/ivad117

357.

Maeda

, Shimamura

, Yoshioka

, et al. Midterm outcomes after surgical aortic valve replacement with the INSPIRIS RESILIA from a multicenter AVR registry. J Cardiol, 2023; 82(4):261–267; doi: 10.1016/j.jjcc.2023.05.012

358.

Mehdiani

, Chekhoeva

, Klein

, et al. The first report of transcatheter aortic valve-in-valve implantation within the expandable Inspiris Resilia(R) bioprosthetic valve. Eur J Cardiothorac Surg, 2022; 62(2):ezac394; doi: 10.1093/ejcts/ezac394

359.

Yao

, Attalla

, Ren

, et al. Ease of use, safety, and efficacy of integra bilayer wound matrix in the treatment of diabetic foot ulcers in an outpatient clinical setting: A prospective pilot study. J Am Podiatr Med Assoc, 2013; 103(4):274–280; doi: 10.7547/1030274

360.

Iacomino

, Fratini

, Sollima

, et al. Surgical resection and immediate reconstruction with a bilayer wound collagen matrix of a rare oral angiosarcoma: A case report. Diseases, 2024; 12(6):117; doi: 10.3390/diseases12060117

361.

Gonzalez

, Castagno

, Carter

, et al. Negative pressure wound therapy on complex extremity wounds requiring coverage with a meshed bilayer wound matrix: A retrospective analysis. J Wound Care, 2022; 31(Sup9):S8–S15; doi: 10.12968/jowc.2022.31.Sup9.S8

362.

Othman

, Lukowiak

, Shakir

, et al. Bilayer wound matrix-based cutaneous scalp reconstruction: A multidisciplinary case control analysis of factors associated with reconstructive success and failure. J Plast Reconstr Aesthet Surg, 2021; 74(11):3008–3014; doi: 10.1016/j.bjps.2021.03.080

363.

Bascone

, Deitermann

, Lin

, et al. Using integra for reconstruction of facial defects after mohs micrographic surgery. Plast Reconstr Surg Glob Open, 2023; 11(12):e5474; doi: 10.1097/GOX.0000000000005474

364.

Shores

, Hiersche

, Gabriel

, et al. Tendon coverage using an artificial skin substitute. J Plast Reconstr Aesthet Surg, 2012; 65(11):1544–1550; doi: 10.1016/j.bjps.2012.05.021

365.

Gabriel

, Thimmappa

, Rubano

, et al. Evaluation of an ultra-lightweight, single-patient-use negative pressure wound therapy system over dermal regeneration template and skin grafts. Int Wound J, 2013; 10(4):418–424; doi: 10.1111/j.1742-481X.2012.00999.x

366.

Koenen

, Felcht

, Vockenroth

, et al. One-stage reconstruction of deep facial defects with a single layer dermal regeneration template. J Eur Acad Dermatol Venereol, 2011; 25(7):788–793; doi: 10.1111/j.1468-3083.2010.03863.x

367.

Muller

, Schiekofer

, Korner

, et al. Improved patient-centered care with effective use of Integra(R) in dermatologic reconstructive surgery. J Dtsch Dermatol Ges, 2013; 11(6):537–548; doi: 10.1111/ddg.12038

368.

Casal-Beloy

, Somoza Argibay

, Garcia-Gonzalez

, et al. Management of recurrent urethrocutaneous fistula after hypospadias surgery in pediatric patients: Initial experience with dermal regeneration sheet Integra. Cir Pediatr, 2017; 30(4):207–210.

369.

Falcone

, Preto

, Ciclamini

, et al. Bioengineered dermal matrix (Integra(R) reduces donor site morbidity in total phallic construction with radial artery forearm free-flap. Int J Impot Res, 2023; doi: 10.1038/s41443-023-00775-5

370.

Bagetala

, Fonseca

, Morton

, et al. Safety and Efficacy KollaGen II-xs: A 60-day Clinical Trial. West Indian Med J, 2023; 70(1):69; doi: 10.7727/wimj.2026.293

371.

Griswold

, Cepica

, Rossi

, et al. A comparison of Xeroform and SkinTemp dressings in the healing of skin graft donor sites. J Burn Care Rehabil, 1995; 16(2 Pt 1):136–140; doi: 10.1097/00004630-199503000-00008

372.

Kolenik

3rd , McGovern

, Leffell

. Use of a lyophilized bovine collagen matrix in postoperative wound healing. Dermatol Surg, 1999; 25(4):303–307; doi: 10.1046/j.1524-4725.1999.08230.x

373.

Sreekumar

, Bhandari

, Praveen

. Comparative study of collagen and paraffin gauze dressing on skin graft donor site. Indian Journal of Burns, 2015; 23(1):81–83; doi: 10.4103/0971-653X.171663

374.

Tseng

, Tsou

, Wang

, et al. Characterization of chitosan-gelatin scaffolds for dermal tissue engineering. J Tissue Eng Regen Med, 2013; 7(1):20–31; doi: 10.1002/term.492

375.

Mulder

, Lee

. A retrospective clinical review of extracellular matrices for tissue reconstruction: Equine pericardium as a biological covering to assist with wound closure. Wounds, 2009; 21(9):254–261.

376.

Fleischli

, Laughlin

, Fleischli

. Equine pericardium collagen wound dressing in the treatment of the neuropathic diabetic foot wound: A pilot study. J Am Podiatr Med Assoc, 2009; 99(4):301–305; doi: 10.7547/0980301

377.

Van Kampen

, Arnoczky

, Parks

, et al. Tissue-engineered augmentation of a rotator cuff tendon using a reconstituted collagen scaffold: A histological evaluation in sheep. Muscles Ligaments Tendons J, 2013; 3(3):229–235.

378.

Paige

, Kremer

, Landry

, et al. Modulation of inflammation in wounds of diabetic patients treated with porcine urinary bladder matrix. Regen Med, 2019; 14(4):269–277; doi: 10.2217/rme-2019-0009

379.

Valerio

, Campbell

, Sabino

, et al. The use of urinary bladder matrix in the treatment of trauma and combat casualty wound care. Regen Med, 2015; 10(5):611–622; doi: 10.2217/rme.15.34

380.

Rommer

, Peric

, Wong

. Urinary bladder matrix for the treatment of recalcitrant nonhealing radiation wounds. Adv Skin Wound Care, 2013; 26(10):450–455; doi: 10.1097/01.ASW.0000434617.57451.e6

381.

Diller

, Tabor

. The Role of the Extracellular Matrix (ECM) in wound healing: A review. Biomimetics (Basel), 2022; 7(3):87; doi: 10.3390/biomimetics7030087

382.

Yousef

MAA

, La Maida

, Misaggi

. Long-term radiological and clinical outcomes after using bone marrow mesenchymal stem cells concentrate obtained with selective retention cell technology in posterolateral spinal fusion. Spine (Phila Pa 1976), 2017; 42(24):1871–1879; doi: 10.1097/BRS.0000000000002255

383.

Carter

, Swearingen

, Chaput

, et al. Clinical and radiographic assessment of transforaminal lumbar interbody fusion using HEALOS collagen-hydroxyapatite sponge with autologous bone marrow aspirate. Spine J, 2009; 9(6):434–438; doi: 10.1016/j.spinee.2008.11.004

384.

Wang

, Strecker

, Liu

, et al. Connective Tissue Growth Factor reporter mice label a subpopulation of mesenchymal progenitor cells that reside in the trabecular bone region. Bone, 2015; 71:76–88; doi: 10.1016/j.bone.2014.10.005

385.

Basile

, Marchegiani

, Novak

, et al. Human amniotic fluid stem cells attract osteoprogenitor cells in bone healing. J Cell Physiol, 2020; 235(5):4643–4654; doi: 10.1002/jcp.29342

386.

Asaad

, Kapur

, Baumann

, et al. Acellular dermal matrix provides durable long-term outcomes in abdominal wall reconstruction: A study of patients with over 60 months of follow-up. Ann Surg, 2022; 276(5):e563–e570; doi: 10.1097/SLA.0000000000004454

387.

Janfaza

, Martin

, Skinner

. A preliminary comparison study of two noncrosslinked biologic meshes used in complex ventral hernia repairs. World J Surg, 2012; 36(8):1760–1764; doi: 10.1007/s00268-012-1576-2

388.

Lineaweaver

. Improvement of success rates for abdominal component reconstructions using bovine fetal collagen. Ann Plast Surg, 2012; 68(5):438–441; doi: 10.1097/SAP.0b013e31824bd75c

389.

DiCosmo

. Edge effect the role of collagen in wound healing. Advances in Skin & Wound Care, 2009; 22(1):12–15.

390.

Ayello

. TIME Heals wounds-advances in modern wound care technologies. Advances in Skin & Wound Care, 2009; 22(1):1; doi: 10.1097/01.ASW.0000305447.48940.f3

391.

Fitzgerald

, Steinberg

. Collagen in wound healing: Are we onto something new or just repeating the past? The Foot and Anckle Online Journal, 2009; 2(9):3; doi: 10.3827/faoj.2009.0209.0003

392.

Almazrooa

, Noonan

, Woo

. Resorbable collagen membranes: Histopathologic features. Oral Surg Oral Med Oral Pathol Oral Radiol, 2014; 118(2):236–240; doi: 10.1016/j.oooo.2014.04.006

393.

Park

, Kim

, Jeong

, et al. Minimally invasive immediate implantation in teeth with gingival recession: 3 case reports. J Dent Implant Res, 2024; 43(2):9–18; doi: 10.54527/jdir.2024.43.2.9

394.

Dagba

, Mourlass

, Durand

, et al. A novel approach to treat large schneiderian membrane perforation -a case series. International Journal of Dentistry and Oral Health, 2015; 1(6); doi: 10.16966/2378-7090.137

395.

Heffner

, Holmes

, Ferrari

, et al. Bone marrow-derived mesenchymal stromal cells and platelet-rich plasma on a collagen matrix to improve fascial healing. Hernia, 2012; 16(6):677–687; doi: 10.1007/s10029-012-0941-2

396.

Liden

, May

. Clinical outcomes following the use of ovine forestomach matrix (endoform dermal template) to treat chronic wounds. Adv Skin Wound Care, 2013; 26(4):164–167; doi: 10.1097/01.ASW.0000428862.34294.d4

397.

Melnychuk

, Servetnyk

, Kosnik

. Extracellular matrix-based collagen dressings for scalp repair following mohs micrographic surgery. Cutis, 2023; 111(5):E33–E35; doi: 10.12788/cutis.0796

398.

Merrilees

, Falk

, Zuo

, et al. Use of versican variant V3 and versican antisense expression to engineer cultured human skin containing increased content of insoluble elastin. J Tissue Eng Regen Med, 2017; 11(1):295–305; doi: 10.1002/term.1913

399.

Devore

, Zhu

, Brooks

, et al. Development and characterization of a rapid polymerizing collagen for soft tissue augmentation. J Biomed Mater Res A, 2016; 104(3):758–767; doi: 10.1002/jbm.a.35599

400.

Tai

, Liao

, Chang

, et al. An evaluation of skin and immunological responses after using a novel cross-linked porcine-based dermal injectable collagen with lidocaine for nasolabial fold correction. J Clin Med, 2024; 13(17):5241; doi: 10.3390/jcm13175241

401.

Chuang

, Lin

, Wu

, et al. Quantitative Assessment of New Frontiers in Dermatochalasis and Periorbital Hyperpigmentation Treatment: The Role of Cross-Linked Porcine Collagen. Aesthetic Plast Surg, 2025; 49(8):2191–2201; doi: 10.1007/s00266-024-04407-1

402.

Yang

, Chang

, Tai

, et al. Evaluation of collagen dermal filler with lidocaine for the correction of nasolabial folds: A randomized, double-blind, multicenter clinical trial. Clin Cosmet Investig Dermatol, 2024; 17:1621–1631; doi: 10.2147/CCID.S447760

403.

Sasse

, Lambin

, Gevorkian

, et al. Long-term clinical, radiological, and histological follow-up after complex ventral incisional hernia repair using urinary bladder matrix graft reinforcement: A retrospective cohort study. Hernia, 2018; 22(6):899–907; doi: 10.1007/s10029-018-1830-0

404.

Sasse

, Warner

, Ackerman

, et al. Parastomal hernia repair with urinary bladder matrix grafts: A case series. Int J Case Rep Images, 2016; 7(2):85–91; doi: 10.5348/ijcri-201604-CS-10065

405.

Riganti

, Ciotola

, Amenabar

, et al. Urinary bladder matrix scaffolds strengthen esophageal hiatus repair. J Surg Res, 2016; 204(2):344–350; doi: 10.1016/j.jss.2016.04.053

406.

Sasse

, Warner

, Ackerman

, et al. Hiatal hernia repair with novel biological graft reinforcement. JSLS, 2016; 20(2):e2016.00016; doi: 10.4293/JSLS.2016.00016

407.

Young

, Jackson

, Ronaghan

, et al. Retrorectus repair of incisional ventral hernia with urinary bladder matrix reinforcement in a long-term porcine model. Regen Med, 2018; 13(4):395–408; doi: 10.2217/rme-2018-0023

408.

Young

, McGilvray

, Ehrhart

, et al. Comparison of in vivo remodeling of urinary bladder matrix and acellular dermal matrix in an ovine model. Regen Med, 2018; 13(7):759–773; doi: 10.2217/rme-2018-0091

409.

Ottenbacher

, Alkildani

, Korzinskas

, et al. Novel histomorphometrical approach to evaluate the integration pattern and functionality of barrier membranes. Dent J (Basel), 2021; 9(11):127; doi: 10.3390/dj9110127

410.

Kolliker

, Hicklin

, Hirsiger

, et al. In vitro evaluation of the permeability of different resorbable xenogeneic membranes after collagenolytic degradation. Membranes (Basel), 2022; 12(8):787; doi: 10.3390/membranes12080787

411.

Neiva

, Pagni

, Duarte

, et al. Analysis of tissue neogenesis in extraction sockets treated with guided bone regeneration: Clinical, histologic, and micro-CT results. Int J Periodontics Restorative Dent, 2011; 31(5):457–469.

412.

Thomas

, Malathi

, Muthukumaraswamy

, et al. Comparative evaluation of concentrated growth factor with bioactive glass and collagen membrane in the treatment of horizontal osseous defects with open flap debridement. Int J of Med Sci Curr Res, 2021; 4(6):698–711.

413.

Pesce

, Zubery

, Goldlust

, et al. Ossification and bone regeneration in a canine GBR model, Part 2: Glycated cross-linked collagenated alloplastic hydroxyapatite scaffold vs non-cross-linked collagenated xenographic bone hydroxyapatite. Int J Oral Maxillofac Implants, 2023; 38(5):923–932; doi: 10.11607/jomi.9822

414.

Chillarge

, O’Neill

, Safranek

. Mid-oesophageal traction diverticulum in a patient with systemic lupus erythematosus. BMJ Case Rep, 2021; 14(4):e238529; doi: 10.1136/bcr-2020-238529

415.

Shikora

, Kim

, Tarnoff

. Comparison of permanent and nonpermanent staple line buttressing materials for linear gastric staple lines during laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis, 2008; 4(6):729–734; doi: 10.1016/j.soard.2008.02.001

416.

Wahab

, Roman

, Chakravarthy

, et al. The use of a pure native collagen dressing for wound bed preparation prior to use of a living Bi-layered skin substitute. J Am Coll Clin Wound Spec, 2014; 6(1–2):2–8; doi: 10.1016/j.jccw.2015.03.002

417.

Lozeau

, Grosha

, Kole

, et al. Collagen tethering of synthetic human antimicrobial peptides cathelicidin LL37 and its effects on antimicrobial activity and cytotoxicity. Acta Biomater, 2017; 52:9–20; doi: 10.1016/j.actbio.2016.12.047

418.

Capella-Monsonis

, Tilbury

, Wall

, et al. Porcine mesothelium matrix as a biomaterial for wound healing applications. Mater Today Bio, 2020; 7:100057; doi: 10.1016/j.mtbio.2020.100057

419.

Shah

, Chakravarthy

. Evaluation of a bovine 100% native collagen for the treatment of chronic wounds: A case series. J Wound Ostomy Continence Nurs, 2015; 42(3):226–234; doi: 10.1097/WON.0000000000000124

420.

Maghsoudi

, Slot

, van der Weijden

FGA

. Bone remodeling around dental implants after 1-1.5 years of functional loading: A retrospective analysis of two-stage implants. Clin Exp Dent Res, 2022; 8(3):680–689; doi: 10.1002/cre2.574

421.

Al-Qutub

, Al-Omar

, Ramalingam

, et al. Guided bone regeneration using biphasic calcium phosphate with adjunct recombinant human bone morphogenetic Protein-2 with and without collagen membrane in standardized calvarial defects in rats: A histologic and biomechanical analysis. Int J Periodontics Restorative Dent, 2016; 36 Suppl:s11–s20; doi: 10.11607/prd.2376

422.

Guerra

, Morais Branco

, Vasconcelos

, et al. Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: An experimental study in a rabbit model. Clin Oral Implants Res, 2011; 22(3):314–322; doi: 10.1111/j.1600-0501.2010.02002.x

423.

Nielsen

, Low

, Chen

, et al. Targeted delivery of abaloparatide to spinal fusion site accelerates fusion process in rats. Biomedicines, 2024; 12(3):612; doi: 10.3390/biomedicines12030612

424.

Baratta

, Superville

. Demonstrating the clinical efficacy of a multi-modality approach to managing various wound aetiologies. Wounds International, 2023; 14(3).

425.

Kiat

, Imran

. The UKM StimuGold (UKMSG) Wound bed preparation method: A unique technique in combining superabsorbent polymer polyacrylate sodium with collagen–Glycerine amorphous base dressing: A case series. Br J Surgical Sci, 2022; 3:71–78.

426.

Faramarzi

, Fatahi

, Rahimi

, et al. Comprehensive infectious diabetic foot ulcer repair through multiple dressing methods, maggot therapy, and vacuum therapy after amputation: A case report study. Int J Surg Case Rep, 2024; 121:109970; doi: 10.1016/j.ijscr.2024.109970

427.

Emami

, Ebrahimi

. Bioactive wound powders as wound healing dressings and drug delivery systems. Powder Technology, 2023:423; doi: 10.1016/j.powtec.2023.118501

428.

Papanas

, Papachristou

, Kefala

, et al. Use of the new vergenix soft tissue repair matrix to heal a chronic neuropathic diabetic foot ulcer. Int J Low Extrem Wounds, 2020; 19(2):205–206; doi: 10.1177/1534734620903597

429.

Ferraro

, Lanzano

, Grella

, et al. Successful treatment of wound dehiscence by innovative type 1 collagen flowable gel: A case report. Plast Reconstr Surg Glob Open, 2022; 10(6):e4360; doi: 10.1097/GOX.0000000000004360

430.

Farkash

, Avisar

, Volk

, et al. First clinical experience with a new injectable recombinant human collagen scaffold combined with autologous platelet-rich plasma for the treatment of lateral epicondylar tendinopathy (tennis elbow). J Shoulder Elbow Surg, 2019; 28(3):503–509; doi: 10.1016/j.jse.2018.09.007

431.

Shilo

, Roth

, Amzel

, et al. Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel. Tissue Eng Part A, 2013; 19(13–14):1519–1526; doi: 10.1089/ten.TEA.2012.0345

432.

Willard

, Drexler

, Das

, et al. Plant-derived human collagen scaffolds for skin tissue engineering. Tissue Eng Part A, 2013; 19(13–14):1507–1518; doi: 10.1089/ten.TEA.2012.0338

433.

Poranki

, Goodwin

, Van Dyke

. Assessment of deep partial thickness burn treatment with keratin biomaterial hydrogels in a swine model. Biomed Res Int, 2016; 2016:1803912; doi: 10.1155/2016/1803912

434.

Liu

, Suarez-Arnedo

, Caston

ELP

, et al. Exploring the role of spatial confinement in immune cell recruitment and regeneration of skin wounds. Adv Mater, 2023; 35(49):e2304049; doi: 10.1002/adma.202304049

435.

Fan Gaskin

, Kong

RCK

, Shah

, et al. Inhibitory Effects of 3′,4’-Dihydroxyflavonol in a mouse model of glaucoma filtration surgery and TGFbeta1-induced responses in human tenon’s fibroblasts. Transl Vis Sci Technol, 2022; 11(8):18; doi: 10.1167/tvst.11.8.18

436.

Kip

, Tao

, Trocha

, et al. Periprocedural hydrogen sulfide therapy improves vascular remodeling and attenuates vein graft disease. J Am Heart Assoc, 2020; 9(22):e016391; doi: 10.1161/JAHA.120.016391

437.

Serala

, Bai

, Prince

. Pyrvinium pamoate alone and with gemcitabine exhibits anti-pancreatic cancer activity in 2D and 3D cell culture models. J Cell Mol Med, 2024; 28(23):e70222; doi: 10.1111/jcmm.70222

438.

Capella-Monsonis

, Kelly

, Kearns

, et al. Decellularised porcine peritoneum as a tendon protector sheet. Biomed Mater, 2019; 14(4):044102; doi: 10.1088/1748-605X/ab2301

439.

Guo

, Dipietro

. Factors affecting wound healing. J Dent Res, 2010; 89(3):219–229; doi: 10.1177/0022034509359125

440.

Dave

, Habte

, Vora

, et al. Sushruta: The Father of Indian surgical history. Plast Reconstr Surg Glob Open, 2024; 12(4):e5715; doi: 10.1097/GOX.0000000000005715

441.

Yannas

, Burke

, Warpehoski

, et al. Prompt, long-term functional replacement of skin. Trans Am Soc Artif Intern Organs, 1981; 27:19–23.

442.

Noordenbos

, Dore

, Hansbrough

. Safety and efficacy of TransCyte for the treatment of partial-thickness burns. J Burn Care Rehabil, 1999; 20(4):275–281; doi: 10.1097/00004630-199907000-00002

443.

Tan

, Chen

, Yan

, et al. Promotion of diabetic wound healing by collagen scaffold with collagen-binding vascular endothelial growth factor in a diabetic rat model. J Tissue Eng Regen Med, 2014; 8(3):195–201; doi: 10.1002/term.1513

444.

Ding

, Xu

, Yan

, et al. Effect of collagen scaffold with Bcl-2-Modified Adipose-derived stem cells on diabetic mice wound healing. Int J Low Extrem Wounds, 2020; 19(2):139–147; doi: 10.1177/1534734619880055

445.

Jana

, Datta

, Das

, et al. Copper and cobalt doped bioactive glass-fish dermal collagen electrospun mat triggers key events of diabetic wound healing in full-thickness skin defect model. J Mech Behav Biomed Mater, 2022; 134:105414; doi: 10.1016/j.jmbbm.2022.105414

446.

Chakrabarti

, Mazumder

, Rajkonwar

, et al. bFGF and collagen matrix hydrogel attenuates burn wound inflammation through activation of ERK and TRK pathway. Sci Rep, 2021; 11(1):3357; doi: 10.1038/s41598-021-82888-9

447.

Salehi

, Hosseinzadeh-Attar

, Alipoor

, et al. Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns. Burns, 2024; 50(2):444–453; doi: 10.1016/j.burns.2023.08.017

448.

Pinard

, Jones

, Milewicz

. Genetics of thoracic and abdominal aortic diseases. Circ Res, 2019; 124(4):588–606; doi: 10.1161/CIRCRESAHA.118.312436

449.

Zuo

, Xiao

, Yang

, et al. Engineering collaen-based biomaterials for cardiovascular medicine. Collagen & Leather, 2024; 6(1):1–23.

450.

Prager

, Polterauer

, Bohmig

, et al. Collagen versus gelatin-coated Dacron versus stretch polytetrafluoroethylene in abdominal aortic bifurcation graft surgery: Results of a seven-year prospective, randomized multicenter trial. Surgery, 2001; 130(3):408–414; doi: 10.1067/msy.2001.115904

451.

Wissink

, Beernink

, Poot

, et al. Improved endothelialization of vascular grafts by local release of growth factor from heparinized collagen matrices. J Control Release, 2000; 64(1–3):103–114; doi: 10.1016/s0168-3659(99)00145-5

452.

Liu

, Zhang

, Wei

, et al. Dressing blood-contacting materials by a stable hydrogel coating with embedded antimicrobial peptides for robust antibacterial and antithrombus properties. ACS Appl Mater Interfaces, 2021; 13(33):38947–38958; doi: 10.1021/acsami.1c05167

453.

Blackburn

, Sofrenovic

, Kuraitis

, et al. Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction. Biomaterials, 2015; 39:182–192; doi: 10.1016/j.biomaterials.2014.11.004

454.

Zheng

, Tan

, Li

, et al. Biotherapeutic-loaded injectable hydrogels as a synergistic strategy to support myocardial repair after myocardial infarction. J Control Release, 2021; 335:216–236; doi: 10.1016/j.jconrel.2021.05.023

455.

Wunderlich

, Suppa

, Gandini

, et al. Risk factors and innovations in risk assessment for melanoma, basal cell carcinoma, and squamous cell carcinoma. Cancers (Basel), 2024; 16(5):1016; doi: 10.3390/cancers16051016

456.

Konya

, Shishido

, Nemoto

, et al. Risk factors of skin barrier dysfunction in older adults: A systematic review. Jpn J Nurs Sci, 2024; 21(3):e12597; doi: 10.1111/jjns.12597

457.

Worrede

, Douglass

, Weeraratna

. The dark side of daylight: Photoaging and the tumor microenvironment in melanoma progression. J Clin Invest, 2021; 131(6):e143763; doi: 10.1172/JCI143763

458.

Rozario

, DeSimone

. The extracellular matrix in development and morphogenesis: A dynamic view. Dev Biol, 2010; 341(1):126–140; doi: 10.1016/j.ydbio.2009.10.026

459.

Liu

, Dong

, Du

, et al. Collagen study advances for photoaging skin. Photodermatol Photoimmunol Photomed, 2024; 40(1):e12931; doi: 10.1111/phpp.12931

460.

Myllyharju

, Kivirikko

. Collagens and collagen-related diseases. Ann Med, 2001; 33(1):7–21; doi: 10.3109/07853890109002055

461.

Neshatian

, Mittal

, Huang

, et al. Investigation of dermal collagen nanostructures in Ehlers-Danlos Syndrome (EDS) patients. PLoS One, 2024; 19(8):e0307442; doi: 10.1371/journal.pone.0307442

462.

Gahlawat

, Siess

, Losada

, et al. Impact of vascular Ehlers-Danlos Syndrome-associated Gly substitutions on structure, function, and mechanics using bacterial collagen. Matrix Biol, 2025; 135:87–98; doi: 10.1016/j.matbio.2024.12.002

463.

Kling

, Torres-Netto

, Abdshahzadeh

, et al. Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas. Sci Rep, 2021; 11(1):17362; doi: 10.1038/s41598-021-96775-w

464.

Morais

, Mota

, Eloy

, et al. Vascular Ehlers-Danlos syndrome: A case with fatal outcome. Dermatol Online J, 2011; 17(4):1.

465.

Malfait

, Wenstrup

, De Paepe

. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genet Med, 2010; 12(10):597–605; doi: 10.1097/GIM.0b013e3181eed412

466.

Mao

, Bristow

. The Ehlers-Danlos syndrome: On beyond collagens. J Clin Invest, 2001; 107(9):1063–1069; doi: 10.1172/JCI12881

467.

Chen

, Yang

, Lovisa

, et al. Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta. Nat Commun, 2021; 12(1):7199; doi: 10.1038/s41467-021-27563-3

468.

Verzijl

, DeGroot

, Thorpe

, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem, 2000; 275(50):39027–39031; doi: 10.1074/jbc.M006700200

469.

Tsurufuji

, Ishibashi

. Glycine-Serum interconversion and collagen biosynthesis in Vivo. possible difference in the amino acid supplying system between skin collagen and serum albumin in Guinea Pigs. J Biochem, 1965; 57:155–160; doi: 10.1093/oxfordjournals.jbchem.a128071

470.

Shoulders

, Raines

. Collagen structure and stability. Annu Rev Biochem, 2009; 78:929–958; doi: 10.1146/annurev.biochem.77.032207.120833

471.

, Wu

. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Amino Acids, 2018; 50(1):29–38; doi: 10.1007/s00726-017-2490-6

472.

Phang

. The regulatory mechanisms of proline and hydroxyproline metabolism: Recent advances in perspective. Front Oncol, 2022; 12:1118675; doi: 10.3389/fonc.2022.1118675

473.

, Fukunaga

, Takenouchi

, et al. Comparative study of the physiological properties of collagen, gelatin and collagen hydrolysate as cosmetic materials. Int J Cosmet Sci, 2005; 27(2):101–106; doi: 10.1111/j.1467-2494.2004.00251.x

474.

Aguirre-Cruz

, Leon-Lopez

, Cruz-Gomez

, et al. Collagen Hydrolysates for skin protection: Oral administration and topical formulation. Antioxidants (Basel), 2020; 9(2):181; doi: 10.3390/antiox9020181

475.

Yazaki

, Ito

, Yamada

, et al. Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated Gly-Pro-Hyp and its hydrolyzed form of Pro-Hyp into the bloodstream and skin. J Agric Food Chem, 2017; 65(11):2315–2322; doi: 10.1021/acs.jafc.6b05679

476.

Agustina

, Miatmoko

, Hariyadi

. Challenges and strategies for collagen delivery for tissue regeneration. J Public Health Afr, 2023; 14(Suppl 1):2505; doi: 10.4081/jphia.2023.2505

477.

Lemperle

, Knapp

, Sadick

, et al. ArteFill permanent injectable for soft tissue augmentation: I. Mechanism of action and injection techniques. Aesthetic Plast Surg, 2010; 34(3):264–272; doi: 10.1007/s00266-009-9413-1

478.

Knapp

, Kaplan

, Daniels

. Injectable collagen for soft tissue augmentation. Plast Reconstr Surg, 1977; 60(3):398–405.

479.

Jia

, Qiu

, Zhang

, et al. Efficacy and safety of Type III Collagen lyophilized fibers using mid-to-deep dermal facial injections for the correction of dynamic facial wrinkles. Aesthetic Plast Surg, 2024; 48(13):2500–2512; doi: 10.1007/s00266-023-03838-6

480.

Lucey

, Goldberg

. Complications of collagen fillers. Facial Plast Surg, 2014; 30(6):615–622; doi: 10.1055/s-0034-1396904

481.

Kroumpouzos

, Treacy

. Hyaluronidase for dermal filler complications: Review of applications and dosage recommendations. JMIR Dermatol, 2024; 7:e50403; doi: 10.2196/50403

482.

Kim

, Kwon

, Hong

, et al. Comparative evaluation of the biodegradability and wrinkle reduction efficacy of human-derived collagen filler and hyaluronic acid filler. Aesthetic Plast Surg, 2019; 43(4):1095–1101; doi: 10.1007/s00266-019-01373-x

483.

Chiang

, Pierone

, Al-Niaimi

. Dermal fillers: Pathophysiology, prevention and treatment of complications. J Eur Acad Dermatol Venereol, 2017; 31(3):405–413; doi: 10.1111/jdv.13977

484.

Rzepniewski

, Zatorski

, Nowak

, et al. Longevity of hyaluronic acid dermal fillers - current state of knowledge. pd, 2024; 111(1):47–51.

485.

Mienaltowski

, Birk

. Structure, physiology, and biochemistry of collagens. Adv Exp Med Biol, 2014; 802:5–29; doi: 10.1007/978-94-007-7893-1_2

486.

Yang

, Chen

. Conservative treatment of tendon injuries. Am J Phys Med Rehabil, 2020; 99(6):550–557; doi: 10.1097/PHM.0000000000001345

487.

, Jiang

, Chen

, et al. The functions and mechanisms of basic fibroblast growth factor in tendon repair. Front Physiol, 2022; 13:852795; doi: 10.3389/fphys.2022.852795

488.

Weber

, Chahal

. Management of rotator cuff injuries. J Am Acad Orthop Surg, 2020; 28(5):e193–e201; doi: 10.5435/JAAOS-D-19-00463

489.

Nejad

, Hamidieh

, Amirkhani

, et al. Update review on five top clinical applications of human amniotic membrane in regenerative medicine. Placenta, 2021; 103:104–119; doi: 10.1016/j.placenta.2020.10.026

490.

Keeley

, Topoluk

, Mercuri

. Tissues reborn: Fetal membrane-derived matrices and stem cells in orthopedic regenerative medicine. Crit Rev Biomed Eng, 2014; 42(3–4):249–270; doi: 10.1615/critrevbiomedeng.2014011591

491.

Bai

, Gao

, Syed

, et al. Bioactive hydrogels for bone regeneration. Bioact Mater, 2018; 3(4):401–417; doi: 10.1016/j.bioactmat.2018.05.006

492.

Blair

, Larrouture

, Li

, et al. Osteoblast differentiation and bone matrix formation in vivo and in vitro. Tissue Eng Part B Rev, 2017; 23(3):268–280; doi: 10.1089/ten.TEB.2016.0454

493.

Abreu

, Ketpura

, Reversade

, et al. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol, 2002; 4(8):599–604; doi: 10.1038/ncb826

494.

Nauth

, McKee

, Einhorn

, et al. Managing bone defects. J Orthop Trauma, 2011; 25(8):462–466; doi: 10.1097/BOT.0b013e318224caf0

495.

Banwart

, Asher

, Hassanein

. Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976), 1995; 20(9):1055–1060; doi: 10.1097/00007632-199505000-00012

496.

Arrington

, Smith

, Chambers

, et al. Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res, 1996; 329(329):300–309; doi: 10.1097/00003086-199608000-00037

497.

Dimitriou

, Mataliotakis

, Angoules

, et al. Complications following autologous bone graft harvesting from the iliac crest and using the RIA: A systematic review. Injury, 2011; 42 Suppl 2:S3–S15; doi: 10.1016/j.injury.2011.06.015

498.

Skaggs

, Samuelson

, Hale

, et al. Complications of posterior iliac crest bone grafting in spine surgery in children. Spine (Phila Pa 1976), 2000; 25(18):2400–2402; doi: 10.1097/00007632-200009150-00021

499.

Younger

, Chapman

. Morbidity at bone graft donor sites. J Orthop Trauma, 1989; 3(3):192–195; doi: 10.1097/00005131-198909000-00002

500.

Pihlstrom

, Michalowicz

, Johnson

. Periodontal diseases. Lancet, 2005; 366(9499):1809–1820; doi: 10.1016/S0140-6736(05)67728-8

501.

Villoria

GEM

, Fischer

, Tinoco

EMB

, et al. Periodontal disease: A systemic condition. Periodontol 2000, 2024; 96(1):7–19; doi: 10.1111/prd.12616

502.

Broers

DLM

, Dubois

, de Lange

, et al. Reasons for tooth removal in adults: A systematic review. Int Dent J, 2022; 72(1):52–57; doi: 10.1016/j.identj.2021.01.011

503.

Stoecklin-Wasmer

, Rutjes

, da Costa

, et al. Absorbable collagen membranes for periodontal regeneration: A systematic review. J Dent Res, 2013; 92(9):773–781; doi: 10.1177/0022034513496428

504.

Udeabor

, Heselich

, Al-Maawi

, et al. Current knowledge on the healing of the extraction socket: A narrative review. Bioengineering (Basel), 2023; 10(10):1145; doi: 10.3390/bioengineering10101145

505.

Pates

, White

, Durkee

, et al. UC-II(R) undenatured type II collagen data show retention during functional food and beverage prototype processing. Data Brief, 2023; 48:109216; doi: 10.1016/j.dib.2023.109216

506.

Liu

, Nikoo

, Boran

, et al. Collagen and gelatin. Annu Rev Food Sci Technol, 2015; 6:527–557; doi: 10.1146/annurev-food-031414-111800

507.

Paul

, Leser

, Oesser

. Significant amounts of functional collagen peptides can be incorporated in the diet while maintaining indispensable amino acid balance. Nutrients, 2019; 11(5):1079; doi: 10.3390/nu11051079

508.

Seong

, Lee

, et al. Low-molecular-weight collagen peptides supplement promotes a healthy skin: A randomized, double-blinded, placebo-controlled study. J Cosmet Dermatol, 2024; 23(2):554–562; doi: 10.1111/jocd.16026

509.

Inoue

, Sugihara

, Wang

. Ingestion of bioactive collagen hydrolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double-blind placebo-controlled clinical study. J Sci Food Agric, 2016; 96(12):4077–4081; doi: 10.1002/jsfa.7606

510.

Kim

, Chung

, Choi

, et al. Oral intake of low-molecular-weight collagen peptide improves hydration, elasticity, and wrinkling in human skin: A randomized, double-blind, placebo-controlled study. Nutrients, 2018; 10(7):826; doi: 10.3390/nu10070826

511.

Lee

, Kim

, Ahn

, et al. Oral intake of collagen peptide NS improves hydration, elasticity, desquamation, and wrinkling in human skin: A randomized, double-blinded, placebo-controlled study. Food Funct, 2023; 14(7):3196–3207; doi: 10.1039/d2fo02958h

512.

Miyanaga

, Uchiyama

, Motoyama

, et al. Oral supplementation of collagen peptides improves skin hydration by increasing the natural moisturizing factor content in the stratum corneum: A randomized, double-blind, placebo-controlled clinical trial. Skin Pharmacol Physiol, 2021; 34(3):115–127; doi: 10.1159/000513988

513.

Rawlings

, Scott

, Harding

, et al. Stratum corneum moisturization at the molecular level. J Invest Dermatol, 1994; 103(5):731–741; doi: 10.1111/1523-1747.ep12398620

514.

Bagheri Miyab

, Alipoor

, Vaghardoost

, et al. The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial. Burns, 2020; 46(1):156–163; doi: 10.1016/j.burns.2019.02.015

515.

Sugihara

, Inoue

, Venkateswarathirukumara

. Ingestion of bioactive collagen hydrolysates enhanced pressure ulcer healing in a randomized double-blind placebo-controlled clinical study. Sci Rep, 2018; 8(1):11403; doi: 10.1038/s41598-018-29831-7

516.

, Huang

, Pu

, et al. Effects of oral collagen for skin anti-aging: A systematic review and meta-analysis. Nutrients, 2023; 15(9):2080; doi: 10.3390/nu15092080

517.

Trentham

, Dynesius-Trentham

, Orav

, et al. Effects of oral administration of type II collagen on rheumatoid arthritis. Science, 1993; 261(5129):1727–1730; doi: 10.1126/science.8378772

518.

Orhan

, Juturu

, Sahin

, et al. Undenatured Type II collagen ameliorates inflammatory responses and articular cartilage damage in the rat model of osteoarthritis. Front Vet Sci, 2021; 8:617789; doi: 10.3389/fvets.2021.617789

519.

Lerman

, Chang

, Konda

, et al. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Integr Med (Encinitas), 2015; 14(5):52–61.

520.

Zhou

, Zhang

, Dai

, et al. The potential of undenatured type II collagen against arthritis: A review. Collagen & Leather, 2024; 6(1):17; doi: 10.1186/s42825-024-00160-y

521.

Gupta

, Canerdy

, Lindley

, et al. Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: Pain evaluation by ground force plate. J Anim Physiol Anim Nutr (Berl), 2012; 96(5):770–777; doi: 10.1111/j.1439-0396.2011.01166.x

522.

Shiojima

, Takahashi

, et al. Efficacy and safety of dietary undenatured type II collagen on joint and motor function in healthy volunteers: A randomized, double-blind, placebo-controlled, parallel-group study. J Am Nutr Assoc, 2023; 42(3):224–241; doi: 10.1080/07315724.2021.2024466

523.

Schon

, Knaub

, Alt

, et al. UC-II Undenatured Type II collagen for knee joint flexibility: A multicenter, randomized, double-blind, placebo-controlled clinical study. J Integr Complement Med, 2022; 28(6):540–548; doi: 10.1089/jicm.2021.0365

524.

Lee

, Kim

, Lee

, et al. AP collagen peptides (APCPs) promote hair growth by activating the GSK-3beta/beta-catenin pathway and improve hair condition. Exp Dermatol, 2024; 33(7):e15137; doi: 10.1111/exd.15137

525.

Hwang

, Park

, Lee

. Hair-growth-promoting effects of the fish collagen peptide in human dermal Papilla Cells and C57BL/6 mice modulating Wnt/beta-Catenin and BMP signaling pathways. Int J Mol Sci, 2022; 23(19):11904; doi: 10.3390/ijms231911904

526.

Harris

, Fonseca

FLA

, Sharp

, et al. Functional characterization of undenatured Type II collagen supplements: Are they interchangeable? J Diet (Suppl 2022); 19(6):717–732; doi: 10.1080/19390211.2021.1931621

527.

Wang

, Yang

, Zhang

, et al. Effects of different mechanical processes on the structural and powdery properties of insoluble undenatured type II collagen. Food Chem, 2023; 406:135068; doi: 10.1016/j.foodchem.2022.135068

528.

Rustad

, Nickles

, McKenney

, et al. Myths and media in oral collagen supplementation for the skin, nails, and hair: A review. J Cosmet Dermatol, 2022; 21(2):438–443; doi: 10.1111/jocd.14567

529.

Alberts

, Bratu

, Niculescu

, et al. Collagen-based wound dressings: Innovations, mechanisms, and clinical applications. Gels, 2025; 11(4):271; doi: 10.3390/gels11040271

530.

Lou

, Xiang

, Zhu

, et al. Evaluating the therapeutic efficacy and safety of alginate-based dressings in burn wound and donor site wound management associated with burn surgery: A systematic review and meta-analysis of contemporary randomized controlled trials. BMC Surg, 2025; 25(1):215; doi: 10.1186/s12893-025-02956-z

531.

, Lu

, Zhao

, et al. Deciphering the wound-healing potential of collagen peptides and the molecular mechanisms: A review. J Agric Food Chem, 2024; 72(47):26007–26026; doi: 10.1021/acs.jafc.4c02960

532.

She

, Liu

, Mu

, et al. Recent advances in collagen-based hydrogels: Materials, preparation and applications. Reactive and Functional Polymers, 2025; 207(106136):106136; doi: 10.1016/j.reactfunctpolym.2024.106136

533.

Wosicka-Frackowiak

, Poniedzialek

, Wozny

, et al. Collagen and its derivatives serving biomedical purposes: A review. Polymers (Basel), 2024; 16(18); doi: 10.3390/polym16182668

534.

Lee

, Lee

, Kim

, et al. Proteoglycan combined with hyaluronic acid and hydrolyzed collagen restores the skin barrier in mild atopic dermatitis and dry, eczema-prone skin: A pilot study. Int J Mol Sci, 2021; 22(19):10189; doi: 10.3390/ijms221910189

535.

Jadach

, Mielcarek

, Osmałek

. Use of collagen in cosmetic products. Curr Issues Mol Biol, 2024; 46(3):2043–2070; doi: 10.3390/cimb46030132

536.

Hasan

, Lewis

, Hernandez

, et al. Layer-by-layer assembly: Advancing skin repair, one layer at a time. RSC Adv, 2025; 15(18):13908–13923; doi: 10.1039/d4ra08115c

537.

Karimzadeh

, Soltani Fard

, Nadi

, et al. Advances in skin gene therapy: Utilizing innovative dressing scaffolds for wound healing, a comprehensive review. J Mater Chem B, 2024; 12(25):6033–6062; doi: 10.1039/d4tb00966e

538.

Machado

, Ribeiro

, Giublin

FCW

, et al. Next-generation wound care: A scoping review on probiotic, prebiotic, synbiotic, and postbiotic cutaneous formulations. Pharmaceuticals (Basel), 2025; 18(5):704; doi: 10.3390/ph18050704

539.

Debnath

, Agrawal

, Jain

, et al. Collagen as a bio-ink for 3D printing: A critical review. J Mater Chem B, 2025; 13(6):1890–1919; doi: 10.1039/d4tb01060d

540.

Haykal

. Emerging and pioneering ai technologies in aesthetic dermatology: Sketching a path toward personalized, predictive, and proactive care. Cosmetics, 2024; 11(6):206.

541.

Ahmed

, Syed

, Raziq

. Smart biomaterials and AI-Driven approaches for the tissue engineering advancement. In: G2024 Global Conference on Wireless and Optical Technologies. 2024;pp. 1–7, doi:10.1109/GCWOT63882.2024.10805669

542.

, Sheng

, Li

, et al. Research progress in hydrogels for cartilage organoids. Adv Healthc Mater, 2024; 13(22):e2400431; doi: 10.1002/adhm.202400431

543.

Clegg

, Adebowale

, Zhao

, et al. Hydrogels in the clinic: An update. Bioeng Transl Med, 2024; 9(6):e10680; doi: 10.1002/btm2.10680

544.

Salih

, Caputo

, Ghorbel

. Recent advances in hydrogel-based 3D bioprinting and its potential application in the treatment of congenital heart disease. Biomolecules, 2024; 14(7):861; doi: 10.3390/biom14070861

545.

Jie

IWK

, Lee

KWA

, Yoon

, et al. Advancements in clinical utilization of recombinant human collagen: An extensive review. Life (Basel), 2025; 15(4):582; doi: 10.3390/life15040582

546.

Guo

, Ma

, Wang

, et al. Status and developmental trends in recombinant collagen preparation technology. Regen Biomater, 2024; 11:rbad106; doi: 10.1093/rb/rbad106

547.

Cheng

, Feng

, Cao

, et al. Efficacy and safety of topical application of plant-based products on skin aging in healthy individuals: A systematic review and meta-analysis of randomized controlled trials. J Cosmet Dermatol, 2025; 24(2):e16710; doi: 10.1111/jocd.16710

548.

Basu

, Banerjee

, Okoro

, et al. Integration of functional polymers and biosensors to enhance wound healing. Adv Healthc Mater, 2024; 13(29):e2401461; doi: 10.1002/adhm.202401461

549.

Amirrah

, Lokanathan

, Zulkiflee

, et al. A comprehensive review on collagen type i development of biomaterials for tissue engineering: From biosynthesis to bioscaffold. Biomedicines, 2022; 10(9):2307; doi: 10.3390/biomedicines10092307