Sustainable natural biopolymers for biomedical applications

Abstract

Biopolymers are materials specifically engineered to interact with biological systems. They can be derived from either natural or synthetic sources, depending on the biological resources used or the manufacturing process employed. Over recent decades, these materials have gained significant popularity within the medical field due to their remarkable attributes such as biodegradability, bioactivity, and compatibility with human tissue. One notable application is their use as scaffolds for bone regeneration. Biopolymers, being renewable biomaterials, provide opportunities for continuous manufacturing and technological progress across various industries. These biomaterials have demonstrated great promise in medical sectors, including nerve regeneration and the production of surgical devices. Additionally, their versatility extends to non-biomedical applications, like food packaging. This paper aims to provide a comprehensive overview of different biopolymers, elucidating their properties, showcasing their latest applications, and delving into the state-of-the-art manufacturing technologies used in their production. Special emphasis is placed on their suitability as bone tissue repair and regeneration scaffolds, owing to their unique properties, which render them an ideal choice for this specific application.

Keywords

Sustainable biopolymers composites’ matrices or reinforcements surface coating technology radiation additive manufacturing bone implant

Introduction

The processing of non-degradable plastics has been a major environmental problem over the last century. This has led to pressure to phase out petroleum-based synthetic plastics and replace them with natural plastics.¹

The concept of the circular economy has evolved into a means of both preserving resources and generating local employment opportunities. This closed-loop system effectively facilitates the cost-effective transformation of materials, whether in their raw form or from recycled sources, into value-added products.^2,3

Within the framework of the circular economy, various additional concepts play integral roles, including life-cycle analysis (LCA), sustainability, eco-friendly chemistry, and the production of non-polluting products.^4–7

As an alternative to synthetic polymers, there is a growing emphasis on producing biopolymers from sustainable biowaste and biomass feedstocks, attracting increasing attention.^8,9 Simultaneously, ongoing research is focused on the development of green composites and nanocomposites derived from natural fibers and biomass, characterized by excellent biodegradability and high biocompatibility.^10–12

These biomaterials are under constant investigation for potential applications in various fields, including medicine, marketing, and transportation systems.^13–16 They can take the form of edible films, emulsions, packaging materials, and medical implants.^17,18 Notably, they have demonstrated their usefulness in critical areas such as organ replacement, wound healing, tissue scaffolding, and pharmaceutical dressings.^19–21

In the field of orthopedics, despite notable advancements in scientific research, surgical intervention remains a necessary approach to address bone deficiencies stemming from conditions like tumors, trauma, or developmental abnormalities. The availability of autografts, which involve harvesting tissue from the patient, is limited, and the use of allografts, which involve harvesting tissue from another person, carries potential risks.^19,22

To ensure the health and well-being of their patients, orthopedic surgeons and specialized engineers have actively explored innovative methods to tackle bone defects. Among these emerging solutions, scaffolding composites, particularly those combining biopolymers and ceramics, have garnered substantial attention. This interest primarily arises from their favorable properties, notably their capacity to enhance bone tissue conductivity and inductivity.^23–25

When it comes to developing innovative treatments for bone defects, several critical factors are meticulously considered. These factors include biodegradability, ensuring that materials naturally break down over time; biocompatibility, ensuring that materials are compatible with the body; and recyclability, highlighting the importance of sustainable materials in these cutting-edge medical solutions.

In this article, we explore the realm of biopolymers in medical applications, with a specific focus on the most commonly used options. Additionally, we provide an overview of recent examples of biocompatible polymer composites, emphasizing their unique characteristics. Obviously, the quality of composite products based on biopolymers is significantly shaped by the selection of manufacturing technology.^26–28 With this in mind, we embark on a comprehensive examination of advanced manufacturing technologies commonly utilized in the production of biopolymer-based composites. This spectrum includes various processes, ranging from surface coating to synthesis and radiation modification (Table 1). Furthermore, we delve into additive manufacturing (AM) techniques, which extend beyond traditional three-dimensional printing to encompass more advanced methods, including four-dimensional and even five-dimensional printing.²⁹

Table 1.

Biomaterial abbreviations.

Abbreviation	Material
CaP	Calcium phosphate
HA	Hydroxyapatite
B-TCP	B-Tricalcium phosphate
PLGA	Poly(lactide-co-glycolide)
PCL	Poly(e-caprolactone)
PDLA	poly (D-Lactide)
PHB	Polyhydroxybutirate
β-TCP/DCPD)-PHBV	Tricalcium phosphate/Dicalcium phosphate-Poly(hydroxybutyrate-co-hydroxyvalerate
PGA	Glycolic acid
PDO	Poly (dioxanone)
PLA	Poly (lactic acid)
PLLA	Poly (L-Lactide)
PEEK	Polyetheretherketone
TiO₂	Titanium dioxide
EDCs	Elastomer-derived ceramics

Biopolymers: Transforming drug delivery and tissue engineering in medical advancements

Biopolymers play a crucial role in drug delivery techniques, dramatically improving the efficacy of bioactive compounds in the treatment of disease.¹⁹ These versatile polymers, derived from a variety of sources including plants, animals, bacteria and agricultural waste, exhibit a fascinating range of characteristics.³⁰ These include high biocompatibility, slow degradation, mechanical flexibility, structural similarity to native tissues, minimal toxicity and inherent bioactivity. Their close resemblance to the extracellular matrix makes them particularly attractive for applications requiring durable, biodegradable solutions, notably in the medical field, where they excel in promoting bone regeneration.^31,32

Various biopolymers have been used as reinforcement or matrix materials to enhance composites for bone regeneration.¹⁸ The overall structure, resilience under adverse conditions and durability of biopolymer-based composites are mainly influenced by the matrix, while fibre reinforcements play a crucial role in determining the stiffness and strength of composites.

For example, chitosan plays an essential role in promoting cell attachment and growth and is widely used as a matrix material for tissue engineering when produced in a porous structure. These biopolymers have significant applications in implants, particularly for the regeneration of bone, ligaments, cartilage, tendons, liver, nerves, stents and skin. There are many documented examples of biopolymer-based matrices specifically designed for bone applications.^33–38 Table 2 provides an overview of the most commonly used biopolymers in tissue engineering, together with their respective properties.

Table 2.

Biopolymers applied in tissue engineering.⁴⁶

Polymers	Salient features
Chitosan^106,107	Chitosan, an exceptional polymer, naturally degrades over time, minimizing environmental impact. Its biocompatible nature reduces adverse reactions and its antibacterial properties inhibit bacterial growth. With cytocompatibility and bioactivity, Chitosan stimulates cell growth and interacts with biological systems, making it versatile and desirable in various fields. Ex: Carboxymethyl Chitosan/Mangosteen¹⁰⁸
Gelatin¹⁰⁹	Gelatin, a bioactive and biocompatible polymer, interacts with biological systems, minimizes adverse reactions, and promotes cell adherence and growth. Its hemocompatibility and anti-thrombogenic properties further enhance its value in blood-contacting applications. Ex: Chitosan/gelatin¹¹⁰
Arabinoxylan¹¹¹	Arabinoxylan, a biocompatible polymer, promotes cell adherence and inhibits bacterial growth. Its bioactive properties stimulate cellular responses, making it promising for cell proliferation and tissue regeneration. Ex: Cereal-derived arabinoxylans¹¹⁵
Collagen¹¹²	Collagen, a biodegradable and fibrous polymer, supports cell proliferation and tissue growth. Its fibrous structure provides strength and stability, making it valuable in tissue engineering and regenerative medicine applications. Collagen’s biodegradability allows for natural degradation over time, reducing its environmental impact. Ex: collagen-hydroxyapatite¹¹³
Xyloglucan¹¹⁴	Xyloglucan, a versatile polymer, promotes cell proliferation and differentiation, making it valuable for tissue engineering applications. It is biodegradable, reducing its environmental impact over time. Additionally, Xyloglucan’s biocompatibility ensures compatibility with living tissues, minimizing adverse reactions. Ex: Xyloglucan-co-Methacrylic Acid/Hydroxyapatite/SiO₂¹¹⁵
Fibrinogen¹¹⁶	Fibrinogen, a biocompatible polymer, exhibits hemocompatibility, making it suitable for applications involving contact with blood. Its ability to support cell proliferation and its biodegradable nature enhance its value in promoting tissue regeneration and compatibility with biological systems. Ex: Fibrinogen/polycaprolactone¹¹⁷
Polyhydroxybutirate¹¹⁸	Polyhydroxybutirate (PHB) is a biocompatible and biodegradable polymer that offers excellent properties for various applications. It demonstrates both bioactivity and adequate mechanical properties, making it a valuable choice in biomedical and tissue engineering fields. Ex: (Tricalcium phosphate/Dicalcium phosphate-Poly(hydroxybutyrate-co-hydroxyvalerate)) (β-TCP/DCPD)-PHBV²⁵
Beta-glucan¹¹⁹	Beta-glucan, a biocompatible and bioactive polymer, exhibits antibacterial properties and adequate mechanical strength, rendering it versatile for diverse applications. Its biodegradability further enhances its appeal, particularly in the fields of biomedical and tissue engineerin. Ex: Grafted Beta-Glucan/Hydroxyapatite¹¹⁹

The growing enthusiasm for biocomposites has led to their adoption in various industries, including automotive, packaging, and home care. By replicating the structure of natural fibers and utilizing biopolymers derived from renewable sources, biocomposites are now poised to be incorporated into everyday consumer products.^39,40

However, despite the numerous advantages associated with natural fibers, such as their widespread availability, non-toxic nature, combustibility, and biodegradability,^41–45 their practical utilization faces challenges arising from variations in quality, the requirement for low processing temperatures, and increased moisture absorption.⁴⁶ In response to these limitations, researchers have dedicated significant efforts to the functionalization of natural fibers, with the goal of creating advanced biopolymer composites strengthened by natural fibers.^47–50

Biocompatible polymer composites for tissue engineering and implant applications

Composite scaffolds are created by combining the characteristics of multiple materials to meet the mechanical and physiological needs of host tissues, which are organized into 3D structures based on organs. Scaffolds with carefully designed microstructures offer structural support and facilitate mass transfer for tissue regeneration. To function successfully, scaffolds must meet specific requirements, including high porosity,⁵¹ pore interconnectivity, appropriate pore size, non-toxicity, biocompatibility, and promotion of cellular interactions for tissue development. They must also possess suitable mechanical and physical properties.^52,53

Poly (α-hydroxy esters), also known as aliphatic polyesters, represent a class of biocompatible and bioresorbable polymers with significant potential for regenerating large tissues.⁵⁴ These materials are increasingly being considered as alternatives for implants and have already found applications in sutures. The polymers in this category include poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (ε-caprolactone) (PCL), poly (dioxanone) (PDO), and poly (trimethylene carbonate) (PTMC).^55–57 Among these, PLA stands out due to its chirality, which allows the mid-chain residues to exist in three enantiomeric states: L-Lactide, D-Lactide, and meso-lactide.⁵⁸ The most commonly used polylactides in this group are poly (L-Lactide) (PLLA) and poly (D-Lactide) (PDLA).^56,59,60

For example, a recent study conducted by Charles et al. demonstrated the improved mechanical properties of poly (lactic acid) (PLA) composites reinforced with poly (L-Lactide) (PLLA) fibers/hydroxyapatite (HA) manufactured using a compaction technique. The study revealed a linear increase in tensile modulus with increasing HA content, with values of 9.7 GPa for 15% HA compared to 8.3 GPa for 0% HA.^60,61

In a similar vein, Chen et al. conducted a study where they utilized braided and multilayered PLA fabric to enhance the mechanical properties of calcium phosphate (CaP) composites, which are prone to brittleness.^60,62

Furthermore, incorporating bioactive glass into self-reinforced PLA (SR-PLA) composites was observed to significantly improve their mechanical properties. This enhancement made the composites more suitable for intervertebral ossification an example of an article made from this composite is the screw.⁶³

Polyetheretherketone (PEEK) composite materials have gained widespread use as implant materials for artificial organs in critical areas of the human body.^64,65 Additionally, the adoption of PEKK as an innovative material for dental implants and restorations has gained prominence.⁶⁶ The development of novel polymer composites has enabled precise control of their mechanical properties, electrical conductivity, and thermal conductivity, allowing for customized designs tailored to specific applications. The availability today of a wide variety of biopolymers, both natural and synthetic, now available, the opportunities for creative applications and advancements in biomaterials have expanded. What’s more, the technical processes for valorizing their performance have become increasingly practical and efficient.⁶⁷

Manufacturing technology of biopolymer composites

The manufacturing technology for polymer composites plays a pivotal role in crafting products with unique attributes, thereby contributing significantly to the advancement of innovative materials. Traditional manufacturing techniques for polymer composites, such as extrusion, injection molding, calendering, and hot-press molding, have earned recognition for their remarkable attributes, including high reproducibility, precise process control, and the capacity to yield top-notch components. These molding techniques have found extensive application in the creation of intricate profiles,⁶⁸ intricate structural elements,⁶⁹ and plates,^70,71 which in turn elevate the performance and longevity of composite materials. Nevertheless, as the complexity of the components escalates, the sustainability of these molding processes presents certain challenges.

To address these challenges, advanced manufacturing technologies for polymer composites have emerged on the scene. Among these innovations are surface coating technology,⁷² along with additive and radiative manufacturing methods. These cutting-edge approaches hold promise in meeting the demands associated with the production of intricate composite structures.^73,74

Surface coating technology

Surface coating is a fundamental manufacturing technique employed to enhance the performance of a base material by applying a thin film onto its surface. This versatile approach finds utility in treating both polymeric and non-polymeric materials.²⁸ In paramedical applications, it is common to coat a polymer matrix with various materials to provide essential protection against degradation caused by pathogens or exposure to corrosive environments.⁷⁵ Diverse surface coating techniques are available, including plasma spraying, magnetization, electrochemical deposition, and Sol-Gel technology.^76–79

For a clearer overview of these techniques and their suitability for specific applications, Table 3 provides a comprehensive breakdown of their advantages and disadvantages.

Table 3.

Characteristics of various coating technologies.²⁸

Surface coating technology	Materials	Advantages	Disadvantages	Applications
Plasma spraying¹²⁰	Polymer composite coatings	High bonding strength, simple operation, good adjustment performance	Many interaction parameters, difficult to paint inside holes	Preparation of polymer coatings to improve the corrosion resistance of the substrate
Magnetron sputtering¹²¹	Polymer metal nanocomposites	Simple equipment, easy to control, strong adhesion, small damage to the substrate, wide range of applicable materials	Difficult and costly preparation of insulator films	Preparation of metal nanofilms on insulating polymer substrates for applications in sensors, reflectors
Electrochemical deposition¹²²	Multiwalled carbon nanotubes polymer composites	Simple operation, high flexibility and reliability	Sensitive to the influence of changes in process parameters	Preparation of carbon nanotube-polymer composite films on metal substrates for the protection of metallic materials in ship hulls
Sol–gel technology¹²³	Nanostructured polymer composites	Good composition control and film homogenisation ability, low temperature	The drying process is prone to cracking, long moulding cycle and high raw material costs	Preparation of polyimide–silicon dioxide composite coating on epoxy resin substrate to improve corrosion resistance

In the field of orthopedic implants, utilizing surface coating technology, Tae-Sik Jang et al. have developed implants that consist of polyether ether ketone (PEEK) filaments reinforced with internal titanium dioxide (TiO₂) nanoparticles, achieved through dopamine-induced polymerization and AM via material extrusion (ME). To enhance both strength and biocompatibility, the PEEK/TiO₂ composite is coated with hydroxyapatite (HA) using radiofrequency (RF) magnetron sputtering (Figure 1). Interestingly, the bond between the HA coating and the TiO₂ nanoparticles embedded in PEEK is stronger than direct coating onto PEEK, indicating the formation of more robust heterogeneous ceramic-polymer interactions.

Figure 1.

Schematic of fabrication procedure of a PEEK/TiO₂/HA 3D-printed implant along with in vivo scaffold implantation in a rabbit.⁸⁰

This innovative approach demonstrates the successful application of surface coating technology in the development of orthopedic implants, combining PEEK reinforcement with TiO₂ nanoparticles and HA coating to enhance performance and biocompatibility.⁸⁰

Radiation synthesis and modification of biopolymers

Radiation treatment of biopolymers, especially when employing gamma irradiation, stands as a widely utilized method for inducing significant biological and chemical transformations within biopolymers and biocomposites that undergo this process.^81,82 Remarkably, this method accomplishes these transformations without necessitating the inclusion of toxic additives, marking a clear departure from conventional chemical techniques.^83–85 Additionally, analogous processes involving alternative curing or treatment sources like UV,⁸⁶ lasers, glow discharge,⁸⁷ visible light, and incoherent dielectric excimer lamps share similarities with irradiation treatment but typically result in comparatively milder changes.^88,89

Furthermore, these techniques offer the potential to introduce a variety of functional groups onto the surfaces of these emerging polymers. These advancements hold significant promise within the realms of biomedicine and biotechnology.⁹⁰

Additive manufacturing

AM is a relatively new digital manufacturing technology that has successfully integrated machines, computers, numerical control, and various materials into advanced manufacturing processes over the past three decades. This technology primarily relies on a layer-by-layer manufacturing approach, predominantly utilizing 3D printing.⁹¹ This transformative technology has reshaped the conventional approach to part design, placing a heightened focus on enhancing performance, thereby revolutionizing today’s manufacturing industry.

While significant strides have been made in the realm of 3D printing, the advent of 4D and 5D printing has ushered in even more innovative possibilities. However, it’s important to note that the practical implementation of 4D and 5D printing technologies is still in its early stages, with current applications primarily limited to high-end customized products.⁹²

AM technology primarily involves the use of forming equipment and materials. As of now, AM materials mainly include polymers, metals, ceramics, and composites.⁹³

Three-dimensional printing

Three-dimensional printing, as shown in Figure 2, is an advanced prototyping technology that constructs objects layer by layer using powdery materials such as metal, plastic, and adhesives, guided by a digital file.²⁸ It’s not a standalone technology but rather a synergy of computer-aided design, laser technology, printing, and numerical control processing.⁹⁴ The continuous evolution of these technologies has led to significant progress in three-dimensional printing, resulting in various methods like fused deposition manufacturing (FDM),⁹⁵ selective laser sintering (SLS),⁹⁶ powder bed and inkjet head 3D printing (3DP),⁹⁷ and stereolithography (SLA).⁹⁸ In FDM, thermoplastic-based polymer composite materials are extruded through a heated nozzle, followed by deposition and solidification.

Figure 2.

3-D printing and Bioprinting.¹⁰⁴

Four-dimensional printing

In the past decade, there have been remarkable advancements in four-dimensional (4D) printing technology, a breakthrough that enables three-dimensional printed products to autonomously change their shape over time. This innovative approach overcomes the constraints of traditional three-dimensional printing by allowing shape transformations in response to external stimuli such as light, electricity, and temperature.⁹⁸

A significant milestone in this field was achieved by Liu et al., who developed the first 4D printing ceramic using nanocomposites (NCs) within an elastomeric poly(dimethylsiloxane) matrix. These NCs can be printed, deformed, and transformed into silicon oxycarbide matrix NCs, thus enabling the creation of intricate ceramic origami and 4D-printed ceramic structures, as shown in Figure 3. This shape-morphing process is achieved by releasing the elastic energy trapped in pre-strained ceramic precursors, which can stretch up to 200% strain.⁶¹ The research on elastomer-derived ceramics (EDCs) opens up new possibilities for creating hybrid soft/rigid structural materials with potential applications in various fields, including bio-implants and bio-inspired structures.⁹⁹

Figure 3.

Four-dimensional printing of elastomer-derived ceramics (EDCs) and origami. Two typical ceramic 4D printing processes (scale bars: 1 cm).¹⁰⁵

Five-dimensional printing

Five-dimensional (5D) printing refers to a printing technology that utilizes five axes to enable printing at any angle. Unlike traditional 3D printing, which is confined to layer-by-layer printing within a plane, 5D printing introduces additional degrees of freedom, expanding its capabilities for more complex and flexible printing, as shown in Figure 4. By incorporating this additional axis, 5D printing opens up new possibilities for manufacturing complex and customized objects.^100,101 It offers enhanced precision and versatility, allowing the production of parts with both high strength and intricate geometries. This technology has the potential to revolutionize industries such as aerospace, automotive, healthcare, and architecture, where the demand for complex and functional components with high strength is substantial.^102,103

Figure 4.

Five-dimensional printed pressure cap.¹⁰¹

In the latest advancements, the fusion of 4D and 5D printing has given rise to the innovative concept of 6D printing technology. By introducing an extra temporal dimension to the core principles of 5D printing, 6D printing revolutionizes the field by enabling printing from any orientation while concurrently tackling the longstanding challenges associated with sluggish 3D printing. This evolution marks a significant leap in AM, pushing the boundaries of what is achievable in the realm of printing technology.

Conclusion

The adoption of biopolymer composites in diverse applications has ushered in a new era of sustainable materials and significantly impacted the biomedical field, highlighting their pivotal role in advancing healthcare. Biopolymers have emerged as critical components in the development of innovative biomedical applications due to their biocompatibility, biodegradability and versatility. These natural polymers have found applications in drug delivery systems, tissue engineering, wound dressings and even as scaffolds for regenerative medicine, highlighting their importance in improving the quality of life for patients worldwide.

One of the remarkable aspects of biopolymer composites is their compatibility with advanced manufacturing processes, including cutting-edge 5D and 6D AM technologies. These revolutionary methods have expanded the horizons of AM by introducing the dimension of time as a variable, allowing materials to transform or adapt over time in response to external stimuli. This is particularly relevant to biomedical applications, where the ability to create dynamic, self-adapting medical devices and implants can lead to breakthroughs in patient care.

As we look ahead, the perspective in manufacturing processes, particularly in the context of biopolymers, is incredibly promising. The synergy of advanced smart materials and AM technologies opens up a wide array of opportunities in the biomedical field, enabling the fabrication of highly customized, patient-specific medical solutions. These advancements not only have the potential to revolutionize treatment methodologies but also hold promise for the commercial sector, with the creation of consumer products that adapt to users’ needs.

However, it is important to acknowledge that several challenges must be addressed to fully harness the potential of biopolymer-based composites in tissue engineering and the broader biomedical field. These challenges include improving the mechanical properties of biopolymer materials, enhancing their long-term stability, and ensuring their regulatory approval for medical use. Nonetheless, the immense benefits offered by biopolymer composites and their integration into advanced manufacturing processes make it evident that the journey towards realizing these innovative solutions is a worthwhile endeavor with substantial rewards. As we continue to explore and refine these technologies, the future of biomedical applications appears brighter than ever, promising enhanced patient care, improved quality of life, and sustainable healthcare innovations.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Trimeche Monia

References

Moshood

Nawanir

Mahmud

, et al.

Sustainability of biodegradable plastics: new problem or solution to solve the global plastic pollution?

Current Research in Green and Sustainable Chemistry 2022; 5: 100273. DOI: 10.1016/j.crgsc.2022.100273

Hong

Chen

EYX

. Chemically recyclable polymers: a circular economy approach to sustainability. Green Chem 2017; 19(16): 3692–3706.

Stahel Walter

. The circular economy. Nature 2016; 531(7595): 435–438.

Andersen

Birgisdottir

Birkved

. Life cycle assessments of circular economy in the built environment—a scoping review. Sustainability 2022; 14: 6887. DOI: 10.3390/su14116887

Van Eygen

Laner

Fellner

, et al. Circular economy of plastic packaging: current practice and perspectives in Austria. Waste management 2018; 14: 55–64.

Mutlu

Barner

(2022), Getting the terms right: green, sustainable, or circular chemistry? Macromol Chem Phys 2018; 223: 2200111. DOI: 10.1002/macp.202200111

Kausar

. Current state-of-the-art of carbonaceous nanofiller coated carbon fiber in polymeric nanocomposites. J Thermoplast Compos Mater. 2022;0(0). doi:10.1177/08927057221139590

Devadas

Khoo

Chia

, et al. Bioresour Technol 2021; 124702.

Singh

Kumar

Singh

. Investigations on 3D printed thermosetting and ceramic-reinforced recycled thermoplastic-based functional prototypes. J Thermoplast Compos Mater. 2021; 34(8): 1103–1122. doi:10.1177/0892705719864623

10.

Lotfi

Dao

, et al. Natural fiber–reinforced composites: a review on material, manufacturing, and machinability. J Thermoplast Compos Mater. 2021; 34(2): 238–284. doi:10.1177/0892705719844546

11.

Horoshenkov

Jin

. The influence of a thin, natural cellulose fibre membrane on the acoustic absorption of a layer of melamine foam. Build Acoust. 2023; 30(2): 127–142. doi:10.1177/1351010X231154171

12.

Raj

SSR

Dhas

JER

Jesuthanam

. Challenges on machining characteristics of natural fiber-reinforced composites – A review. J Reinforc Plast Compos. 2021; 40(1–2): 41–69. doi:10.1177/0731684420940773

13.

Ahmad

Chhipi-Shrestha

Hewage

, et al. A comprehensive review on construction applications and life cycle sustainability of natural fiber biocomposites. Sustainability 2022; 14: 15905. DOI: 10.3390/su142315905

14.

Viglianisi

Santonocito

Lupi

, et al. Impact of local drug delivery and natural agents as new target strategies against periodontitis: new challenges for personalized therapeutic approach. Therapeutic Advances in Chronic Disease. 2023; 14. doi:10.1177/20406223231191043

15.

Zaman

Khan

. Acetylation used for natural fiber/polymer composites. J Thermoplast Compos Mater. 2021; 34(1): 3–23. doi:10.1177/0892705719838000

16.

Tamta

Palsule

. Kenaf fiber reinforced chemically functionalized styrene-acrylonitrile composites. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231168560

17.

Majeed

Dar

Pandey

Kumar Dash

Srivastava

, et al. Role of additives in starch-based edible films and coating: a review with current knowledge. Prog Org Coating 2023; 181: 107597. doi: 10.1016/j.porgcoat.2023.107597

18.

Mihankhah

Azdast

Mohammadzadeh

, et al. Fused filament fabrication of biodegradable polylactic acid reinforced by nanoclay as a potential biomedical material. J Thermoplast Compos Mater. 2023; 36(3): 961–983. doi:10.1177/08927057211044185

19.

Baranwal

Barse

Fais

, et al. Biopolymer: a sustainable material for food and medical applications. Polymers. 2022; 14(5): 983. doi: 10.3390/polym14050983

20.

Monia

Ridha

. Polymer-ceramic composites for bone challenging applications: materials and manufacturing processes. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231190066

21.

Negut

Dorcioman

Grumezescu

. Scaffolds for wound healing applications. Polymers. 2020; 12(9): 2010. doi: 10.3390/polym12092010

22.

Wang

Yeung

KWK

. Bone grafts and biomaterials substitutes for bone defect repair: a review. Bioact Mater 2017; 2(4): 224–247. doi: 10.1016/j.bioactmat.2017.05.007

23.

Radulescu

Neacsu

Grumezescu

, et al. Novel trends into the development of natural hydroxyapatite-based polymeric composites for bone tissue engineering. Polymers. 2022; 14(5): 899. doi: 10.3390/polym14050899

24.

Shah

Mao

Shih

, et al. An injectable bone marrow‐like scaffold enhances T cell immunity after hematopoietic stem cell transplantation. Nat Biotechnol 2019; 37: 293–302.

25.

Monia

Hichem

Ridha

, et al. Elaboration and evaluation of a composite bone substitute based on β-TCP/DCPD and PHBV, preliminary results. Biomedical Engineering: Applications, Basis, and Communications 2016; 28(5): 1650031.

26.

Mohandesnezhad

Etminanfar

Mahdavi

, et al. Enhanced bioactivity of 316L stainless steel with deposition of polypyrrole/hydroxyapatite layered hybrid coating: Orthopedic applications. Surf. Interfaces 2022; 28, 101604.

27.

Pang

Zhitomirsky

Electrodepostion of nanocomposite organic-inorganic coatings for biomedical applications, International. J. Nanosci 2005; 4: 409–418.

28.

Wang

, et al. Manufacturing technologies of polymer composites—a review. Polymers 2023; 15: 712. DOI: 10.3390/polym15030712

29.

Rouf

Malik

Singh

, et al. Additive manufacturing technologies: industrial and medical applications. Sustainable Operations and Computers 2022; 3: 258–274. DOI: 10.1016/j.susoc.2022.05.001

30.

Yashas Gowda

Ballupete Nagaraju

, et al. Biopolymer-based composites: an eco-friendly alternative from agricultural waste biomass. J. Compos. Sci 2023; 7: 242. DOI: 10.3390/jcs7060242

31.

Mohanty

Misra

Drzal

. Natural fibers, biopolymers, and Biocomposites. CRC press, 2005.

32.

Pramanik

Kharche

, et al. Natural biopolymers for bone tissue engineering: a brief review. Engineered Regeneration 2023; 4(2): 193–204. DOI: 10.1016/j.engreg.2022.12.002

33.

Song

Shafiq

, et al. 2023. Peptides-tethered vascular grafts enable blood vessel regeneration via endogenous cell recruitment and neovascularization. Compos B Eng 252: 110504. doi: 10.1016/j.compositesb.2023.110504

34.

Wang

Wei

Dong

, et al. 2023. 3D printing of lithium osteogenic bioactive composite scaffold for enhanced bone regeneration. Compos B Eng 256: 110641. doi: 10.1016/j.compositesb.2023.110641

35.

Wei

Rui-Xia

Quan

, et al. 2023. Gallium-niobium nanofiber surface of niobium/pekk composite with anti-inflammatory, osteogenesis and anti-bacterial effects for facilitating osteoblastic differentiation and ameliorating osteointegration.” Compos B Eng 248: 110375. doi: 10.1016/j.compositesb.2022.110375

36.

Dubey

Kesarwani

Verma

. Incorporation of graphene nanoplatelets/hydroxyapatite in PMMA bone cement for characterization and enhanced mechanical properties of biopolymer composites. J Thermoplast Compos Mater. 2023; 36(5): 1978–2008. doi:10.1177/08927057221086833

37.

Monia

. β-TCP/DCPD-PHBV (40%/60%): biomaterial made from bioceramic and biopolymer for bone regeneration; investigation of intrinsic properties. J Appl Biomater Funct Mater. 2022; 20: 22808000221088950. doi: 10.1177/22808000221088950

38.

Husain

Singh

Pabla

. On compressive properties of 3D printed polyvinylidene fluoride composite for implant applications. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231200005

39.

Aaliya

Sunooj

Lackner

(2021) Biopolymer composites: a review, International Journal of Biobased Plastics 2021; 3(1): 40–84. DOI: 10.1080/24759651.2021.1881214

40.

Ogunbode

Nyakuma

Lawal

, et al. (2022) Morphological, microstructure, tensile and water-sorption characteristics of surface modified kenaf fibre for sustainable biocomposite reinforcement. J Nat Fibers 2022; 19: 7174–7185.

41.

Feng

. Chemical and biochemical basis of cell-bone matrix interaction in health and disease. Curr Chem Biol. 2009; 3(2): 189–196. doi: 10.2174/187231309788166398

42.

Bari

Sistani

Morrell

, et al. Current strategies for the production of sustainable biopolymer composites. Polymers 2021; 13: 2878. DOI: 10.3390/polym13172878

43.

Aslam Khan

Abd Razak

Al Arjan

, et al. Recent advances in biopolymeric composite materials for tissue engineering and regenerative medicines: a review. Molecules. 2021;26(3): 619. doi: 10.3390/molecules26030619

44.

Nair

B Joseph

(2014). Eco-friendly bio-composites using natural rubber (NR) matrices and natural fiber reinforcements. 10.1533/9780857096913.2.249

45.

Makinde-Isola

Taiwo

Oladele

, et al. Development of sustainable and biodegradable materials: a review on banana and sisal fibre based polymer composites. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231186324

46.

Cui

Gao

Zhang

, et al. Study on the moisture absorption and thermal properties of hygroscopic exothermic fibers and related interactions with water molecules. Polymers 2020; 12: 98. DOI: 10.3390/polym12010098

47.

Kufel

Kuciel

Hybrid composites based on polypropylene with basalt/hazelnut shell fillers: the influence of temperature, thermal aging, and water absorption on mechanical properties. Polymers 2020; 12: 18. DOI: 10.3390/polym12010018

48.

Lee

Koay

Chan

, et al. Properties of poly(lactic acid)/durian husk fiber biocomposites: effects of fiber content and processing aid. J Thermoplast Compos Mater. 2020; 33(11): 1518–1532. doi:10.1177/0892705719831734

49.

Craciun

Manaila

Ighigeanu

, et al. A method to improve the characteristics of epdm rubber based eco-composites with electron beam. Polymers 2020; 12: 215. DOI: 10.3390/polym12010215

50.

Jagadish Rajakumaran

Ray

. Investigation on mechanical properties of pineapple leaf–based short fiber–reinforced polymer composite from selected Indian (northeastern part) cultivars. J Thermoplast Compos Mater. 2020; 33(3): 324–342. doi:10.1177/0892705718805535

51.

Krishani

Shin

Suhaimi

, et al. Development of scaffolds from bio-based natural materials for tissue regeneration applications: a review. Gels 2023; 9: 100. DOI: 10.3390/gels9020100

52.

Chocholata

Kulda

Babuska

. Fabrication of scaffolds for bone-tissue regeneration. Materials. 2019; 12(4): 568. doi: 10.3390/ma12040568

53.

Park

S-B

Lih

Park

K-S

, et al. Biopolymerbased functional composites for medical applications. Prog Polym Sci 2017; 68: 77–105.

54.

Rydz

Sikorska

Kyulavska

, et al. Polyester-based (bio)degradable polymers as environmentally friendly materials for sustainable development. Int J Mol Sci. 2014; 16(1): 564–596. doi: 10.3390/ijms16010564

55.

Nair

Laurencin

. Biodegradable polymers as biomaterials. Prog Polym Sci. 2007; 32: 762–798.

56.

Nair

Laurencin

. Polymers as biomaterials for tissue engineering and controlled drug delivery. In: Lee

Kaplan

, (eds). Tissue Engineering I. Springer Berlin Heidelberg, 2006, pp. 47–90.

57.

Wang

, et al. Biocompatibility and degradation studies of poly(L-lactide-co-trimethylene carbonate) copolymers as cardiac occluders. Materialia 2019; 7: 100414.

58.

Madhavan Nampoothiri

Nair

John

. An overview of the recent developments in polylactide (PLA) research. Bioresour Technol. 2010; 101: 8493–8501.

59.

Trimeche

. Biomaterials for bone regeneration: an overview. 2017; DOI: 10.15761/BTT.1000107

60.

Narayanan

Vernekar

Kuyinu

, et al. Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering. Adv Drug Deliv Rev. 2016; 107: 247–276. doi: 10.1016/j.addr.2016.04.015

61.

Charles

Kramer

Shaw

, et al. Self-reinforced composites of hydroxyapatite-coated PLLA fibers: fabrication and mechanical characterization. J Mech Behav Biomed Mater. 2013; 17: 269–277.

62.

Chen

Yang

, et al. Comparison and preparation of multilayered polylactic acid fabric strengthen calcium phosphate-based bone substitutes for orthopedic applications. J Artif Organs. 2016; 19(1): 70–79.

63.

Ella

Kellomaki

Tormala

. In vitro properties of PLLA screws and novel bioabsorbable implant with elastic nucleus to replace intervertebral disc. J Mater Sci Mater Med. 2005; 16: 655–662.

64.

Maruthi

Faisal

Raghavendra

. Conducting polymer based composites as efficient EMI shielding materials: A comprehensive review and future prospects. Synth Met 2021; 272: 116664.

65.

Kumar

Moharana

Kumar

. Current trends in spinel based modified polymer composite materials for electromagnetic shielding. Mater Today Chem 2020; 17: 100346.

66.

Farea

Mohammed

Shirsat

, et al. Hazardous gases sensors based on conducting polymer composites. Chem Phys Lett 2021; 776: 138703.

67.

Flórez

Cazón

Vázquez

. Selected biopolymers’ processing and their applications: a review. Polymers. 2023; 15(3): 641. doi: 10.3390/polym15030641

68.

Zhang

Zhou

. Short fiber reinforced geopolymer composites manufactured by extrusion. J Mater Civ Eng 2005; 17: 624–631.

69.

Liu

. Injection molding in polymer matrix composites. Manuf. Tech. Polym. Matrix Compos 2012; 15–46.

70.

Bryant

. Polyimides. Encycl. Polym. Sci. Technol 2002, 529–555.

71.

Ward

Hine

The science and technology of hot compaction. Polymer 2004; 45: 1413–1427.

72.

Alizadeh-Osgouei

Wen

. A comprehensive review of biodegradable synthetic polymer-ceramic composites and their manufacture for biomedical applications. Bioact Mater 2019; 4: 22–36.

73.

Thiruchitrambalam

Kumar

Shanmugam

, et al. A review on PEEK composites–Manufacturing methods, properties and applications. Mater Today Proc 2020; 33: 1085–1092.

74.

Alshahrani

. Review of 4D printing materials and reinforced composites: behaviors, applications and challenges. J. Sci. Adv. Mater. Devices 2021; 6: 167–185.

75.

Inamuddin Boddula

Ahamed

Asiri

. Polymers Coatings: Technology and Applications. Boca Raton, FL: CRC Press, 2020.

76.

Heimann

. Thermal spraying of biomaterials. Surf Coat Technol 2006; 201: 2012–2019.

77.

Jinho

Kwangmin

Jeongtae

, et al. Hydroxyapatite coatings on nanotubular titanium dioxide thin films prepared by radio frequency magnetron sputtering. J Nanosci Nanotechnol 2013; 13: 5807–5810.

78.

Boccaccini

Keim

, et al. Electrophoretic deposition of biomaterials. J R Soc Interface 2010; 7: 581–613.

79.

Layrolle

Ito

Tateishi

. Sol-gel synthesis of amorphous calcium phosphate and sintering into microporous hydroxyapatite bioceramics. J Am Ceram Soc 1998; 81: 1421–1428.

80.

Jang

T-S

Park

Lee

, et al. Topography-supported nanoarchitectonics of hybrid scaffold for systematically modulated bone regeneration and remodeling. Adv Funct Mater 2022; 32: 2206863. DOI: 10.1002/adfm.202206863

81.

Naikwadi

Sharma

Bhatt

, et al. (2022). Gamma radiation Processed polymeric materials for high performance applications: a review. Front Chem. 2022; 10. DOI: 10.3389/fchem.2022.837111

82.

Esmaielzadeh

Ahmadizadegan

. Gas permeation, thermal, morphology and mechanical properties of polyimide/clay nanocomposites: Effect of organically modified montmorillonite. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231176421

83.

Chang

Guo

Zhang

(2023). Radiation shielding polymer composites: ray-interaction mechanism, structural design, manufacture and biomedical applications. Mater Des 2023; 233: 112253. DOI: 10.1016/j.matdes.2023.112253

84.

Fathy

Ibrahim

Elnaggar

, et al. Polypropylene based bio-composites for packaging materials: physico-mechanical impacts of prepared hyper-branched polyamidoamine and gamma-irradiation. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231169902

85.

Fathy

Elnaggar

Sharaf

. Novel electromagnetic interference shield developed by gamma irradiation of strengthened WPE/WEPDM thermoplastic elastomer with carbon nanotubes. J Thermoplast Compos Mater. 2023; 36(9): 3673–3697. doi:10.1177/08927057221133092

86.

Wang

Shi

Fan

, et al. 2020. Distributed mobile ultraviolet light sources driven by ambient mechanical stimuli. Nano Energy 2020; 74: 104910. doi: 10.1016/j.nanoen.2020.104910

87.

Nevar

Nedelko

Radomtseu

et al. Synthesis of iron oxyhydroxide nanostructures in glow-discharge plasma at atmospheric pressure. J Appl Spectrosc 2023; 90, 599–606. DOI: 10.1007/s10812-023-01571-1

88.

Zhao

, et al. (2020). In vitro antibacterial properties of MoO3/SiO2/Ag2O nanocomposite coating prepared by double cathode glow discharge technique. Surf Coating Technol 2020; 397: 125992.

89.

O’Mahoney

Wood

Ibbotson

, et al. 2022. Potential Harm to the Skin from Unfiltered Krypton Chloride ‘Far-Ultraviolet-C’ Lamps, Even below an Occupational Exposure Limit. J Radiol Prot 2022; 42(4): 043501. doi: 10.1088/1361-6498/ac9e60

90.

Abdel-Ghaffar

. Radiation synthesis and modification of biopolymers and polymeric composites for biomedical applications. Polym Polym Compos 2023; 31. doi:10.1177/09673911231166636

91.

ISO/ASTM 52900 . Additive Manufacturing-General Principles-Fundamentals and Vocabulary. Dublin, Ireland: National Standards Authority of Ireland, 2021.

92.

Kumar

Roy

Hegde

, et al. Chapter 8–4D and 5D printing: Healthcare’s new edge. In 3D Printing Technology in Nanomedicine; Amsterdam, The Netherlands: Elsevier, 2019; pp. 143–163.

93.

Shi

Yan

Zhou

, et al. Overview of additive manufacturing technology and materials, In 3D Printing Technology Series, Materials for Additive Manufacturing, Academic Press, 2021, 1–8. DOI: 10.1016/B978-0-12-819302-0.00001-8

94.

Gibson

Rosen

Stucker

Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing, 2nd ed. Berlin, Germany: Springer, 2015.

95.

Mustapha

Metwalli

A review of fused deposition modelling for 3D printing of smart polymeric materials and composites. Eur Polym J 2021; 156: 110591.

96.

Kenzari

Bonina

Dubois

, et al. Quasicrystal–polymer composites for selective laser sintering technology. Mater Des 2012; 35: 691–695.

97.

Graf

Bermejo

Martinez

, et al. Polymer-ceramic-composites for 3D inkjet printing. In Proceedings of the Mikro System Technik 2017 Congress, München, Germany, 23–25 October 2017; pp. 1–4.

98.

Mahmood

Akram

Chen

, et al. On the evolution of additive manufacturing (3d/4d printing) technologies: materials, applications, and challenges. Polymers 2022; 14: 4698. DOI: 10.3390/polym14214698

99.

Nagarajan

Mertiny

Qureshi

. Magnetically loaded polymer composites using stereolithography—Material processing and characterization. Mater Today Commun 2020; 25: 101520.

100.

Georgantzinos

Giannopoulos

Bakalis

. Additive manufacturing for effective smart structures: the idea of 6D printing. J. Compos. Sci 2021; 5: 119. DOI: 10.3390/jcs5050119

101.

Sadiq

Patil

. Review on 4D and 5D printing technology. Int. Res. J. Eng. Technol 2020; 7: 744–751.

102.

Reddy

Devi

. Review on the advancements of additive manufacturing-4D and 5D printing. Int J Mech Prod Eng Res Dev 2018; 8: 397–402.

103.

Georgantzinos

Giannopoulos

Bakalis

. Additive manufacturing for effective smart structures: the idea of 6D printing. J. Compos. Sci 2021; 5: 119.

104.

Mason

Visintini

Quay

. An overview of clinical applications of 3-D printing and bioprinting. 2019. In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016; 175. https://www.ncbi.nlm.nih.gov/books/NBK542711/

105.

Liu

Zhao

, et al. Origami and 4D printing of elastomer-derived ceramic structures. Sci Adv 2018; 4: eaat0641.

106.

Jindal

Mondal

Bhattacharya

. An in vitro evaluation of zinc silicate fortified chitosan scaffolds for bone tissue engineering. Int J Biol Macromol 2020; 164: 4254–4262. doi: 10.1016/j.ijbiomac.2020.09.018

107.

Aghayan

Seyfi

Asadollahzadeh

, et al. Preparation and characterization of antibacterial chitosan nanocomposites loaded with cellulose/chitosan nanofibers and essential oils. Polym Polym Compos. 2022;30. doi:10.1177/09673911221098732

108.

Chaiwong

Phimolsiripol

Leelapornpisid

, et al. Synergistics of carboxymethyl chitosan and mangosteen extract as enhancing moisturizing, antioxidant, antibacterial, and deodorizing properties in emulsion cream. Polymers. 2022; 14(1): 178. doi: 10.3390/polym14010178

109.

Olad

Hagh

HBK

. Graphene oxide and amin-modified graphene oxide incorporated chitosan-gelatin scaffolds as promising materials for tissue engineering. Compos. Part. B Eng 2019; 162: 692–702. doi: 10.1016/j.compositesb.2019.01.040

110.

Guillén-Carvajal

Valdez-Salas

Beltrán-Partida

, et al. Chitosan, gelatin, and collagen hydrogels for bone regeneration. Polymers. 2023; 15(13): 2762. doi: 10.3390/polym15132762

111.

Wang

Bai

Fan

, et al. Cereal-derived arabinoxylans: structural features and structure-activity correlations. Trends Food Sci Technol 2020; 96: 157–165. doi: 10.1016/j.tifs.2019.12.016

112.

Song

Gao

, et al. Zinc silicate/nano-hydroxyapatite/collagen scaffolds promote angiogenesis and bone regeneration via the p38 MAPK pathway in activated monocytes. ACS Appl Mater Interfaces 2020; 12: 16058–16075. doi: 10.1021/acsami.0c00470

113.

Antoniac

Vasile

, et al. 2021. In vitro characterization of novel nanostructured collagen-hydroxyapatite composite scaffolds doped with magnesium with improved biodegradation rate for hard tissue regeneration. Bioact Mater 6(10): 3383–3395. doi: 10.1016/j.bioactmat.2021.02.030

114.

Aslam Khan

Mehboob

Abd Razak

, et al. Development of polymeric nanocomposite (xyloglucan-co-methacrylic acid/hydroxyapatite/SiO2) scaffold for bone tissue engineering applications—in-vitro antibacterial, cytotoxicity and cell culture evaluation. Polymers. 2020; 12: 1238. doi: 10.3390/polym12061238

115.

Khan

MUA

Hassan

Izwan Abd Razak

Yazid Yahya

Yusof

Ramlee

Joseph Sahaya Anand

Hassan

Aziz

Amin

. 2020. Development of polymeric nanocomposite (xyloglucan-co-methacrylic acid/hydroxyapatite/sio2) scaffold for bone tissue engineering applications—in-vitro antibacterial, cytotoxicity and cell culture evaluation. Polymers 12(6): 1238. doi: 10.3390/polym12061238

116.

Woods

Black

Molloy

, et al. Fabrication of blood-derived elastogenic vascular grafts using electrospun fibrinogen and polycaprolactone composite scaffolds for paediatric applications. J. Tissue Eng. Regen. Med 2020; 14: 1281–1295. doi: 10.1002/term.3100

117.

Alharbi

Brigham

Guthold

. The mechanical properties of blended fibrinogen:polycaprolactone (pcl) nanofibers. Nanomaterials (Basel). 2023; 13(8): 1359. doi: 10.3390/nano13081359

118.

Monia

Ridha

Hassib

. Composite cement embedded in a biopolymer matrix for bone tissue regeneration. J Thermoplast Compos Mater. 2023;0(0). doi:10.1177/08927057231153858

119.

Khan

MUA

Al-Thebaiti

Hashmi

, et al. Synthesis of silver-coated bioactive nanocomposite scaffolds based on grafted beta-glucan/hydroxyapatite via freeze-drying method: anti-microbial and biocompatibility evaluation for bone tissue engineering. Materials. 2020; 13: 971. doi: 10.3390/ma13040971

120.

Bakhsheshi-Rad

Hamzah

Bagheriyan

, et al. Preparation and performance of plasma/polymer composite coatings on magnesium alloy. J Mater Eng Perform 2016; 25: 3948–3959.

121.

Schürmann

Takele

Zaporojtchenko

, et al. Optical and electrical properties of polymer metal nanocomposites prepared by magnetron co-sputtering. Thin Solid Film. 2006; 515: 801–804.

122.

Samal

Besra

Singh

, et al. Multi-walled carbon nanotubes polymer composites by electrophoretic deposition. In: Proceedings of the 2011 International Conference on Nanoscience, Technology and Societa Implications, Bhubaneswar, India, 8–10 December 2011.

123.

Mascia

Lavorgna

. Nanostructured polymer composites by sol–gel method. Wiley Encycl. Compos 2011; 1–20.