Inorganic Chiral Nanomaterials in Tissue Engineering Applications: Mini Review

Abstract

All inorganic nanomaterials such as gold, silica, and cobalt oxide nanoparticles are transforming tissue engineering by providing enantioselective properties with unique characteristics that are mimicking the chirality of biological systems, allowing the precise modulation of cellular behaviors like differentiation and alignment. It is essential for the regeneration of complex tissues such as bone, cartilage, and neural networks, but their clinical application is being obstructed by considerable challenges such as the inability to sustain consistent chirality during synthesis. There are limited means to characterize their molecular structure, the high cost of their production, which constrains their scalability, and the long-term biocompatibility. There are different concerns of these materials in physiological environments, which call for novel solutions such as machine learning-aided synthesis, bioinspired mineralization, and interfacing with cutting-edge technologies such as 3D and 4D bioprinting to design biomimetic scaffolds that facilitate enhanced tissue regeneration. The personalized strategies that are modifying nanomaterial properties to match the distinct requirements of individual patients have the promise of enhancing therapeutic outcomes, and collaborations among materials science, bioengineering, and clinical expertise are needed to standardize protocols, overcome regulatory barriers, and tap the full potential of these nanomaterials. This review is hence a critical appraisal of their revolutionary potential, present limitations, and future promise in enhancing regenerative medicines.

Impact Statement

The research on inorganic chiral nanomaterials in tissue engineering, as presented in the mini review, highlights their unique ability to mimic biological chirality, enhancing cell-scaffold interactions and tissue regeneration. These nanomaterials offer precise control over cellular behavior, improving biocompatibility and functionality in applications such as bone, cartilage, and neural tissue engineering. Their potential to revolutionize the field lies in tailoring chirality for specific tissue responses, advancing personalized medicine and regenerative therapies. This work underscores the need for further exploration into scalable synthesis and clinical translation, paving the way for innovative solutions in tissue engineering and regenerative medicine.

Keywords

chiral inorganic nanomaterials light-mediated chirality induction chiral template chiral scaffolds

Introduction

Tissue engineering integrates scaffolds, cellular components, and bioactive moieties to repair damaged organs or tissue, thereby treating conditions such as bone defects, cardiovascular disease, and neural trauma. Scaffolding design is most important as scaffolds offer a three-dimensional (3D) framework that supports cell adhesion, proliferation, and differentiation. Nanomaterials have transformed scaffold design as they offer a high surface-to-volume ratio, tunable properties, and the capacity to mimic the nanoscale organization of the extracellular matrix (ECM). Inorganic nanomaterials such as gold nanoparticles (AuNPs), quantum dots (QDs), and magnetic nanoparticles (NPs) improve scaffold functionality by offering enhanced mechanical strength, biocompatibility, and bioactivity. The materials can also be used for drug delivery, imaging, and real-time monitoring of tissue regeneration processes. The addition of chirality to inorganic nanomaterials further increases their applications by providing stereospecific interaction with the biological environment, thus enabling accurate control of cellular response and tissue growth.¹

Chirality is a ubiquitous feature of biological systems, occurring at the cellular, tissue, and molecular levels. Most biomolecules, including amino acids, sugars, and DNA, are chiral with homochirality (e.g., L-amino acids and D-sugars) characterizing the biochemical reactions necessary for life.² Chirality refers to a property of an object or molecule that means it cannot be superimposed on its mirror image in the same way a left hand doesn’t fit well into a right-handed glove. For instance, alanine is an amino acid that exists as the enantiomers L-alanine and D-alanine. These two enantiomers are mirror images, with the same chemical makeup but different 3D arrangements. Enantioselectivity, on the other hand, is when there is a preferential interaction of one enantiomer over another with respect to a biological system (a protein binding to L-alanine stronger than D-alanine because of stereospecific recognition). Enantioselectivity can be utilized in tissue engineering when using chiral nanomaterials to influence cellular behavior because enantioselectivity can be used to drive specific pathways of cell adhesion or differentiation. At the cellular level, chirality characterizes processes such as adhesion, migration, and differentiation, where cells respond to chiral microenvironmental cues. The asymmetrical heart development example being one such case of chirality at the cellular level to establish a right-handed cardiac loop.^3,4

Chiral inorganic nanomaterials such as chiral gold nanocrystals, semiconductor QDs, and magnetic NPs have been of special interest in biomedicine due to their chiroptical, physical, and chemical properties. In contrast to organic chiral materials, inorganic nanomaterials possess high dissymmetry factors (g-factors), broad spectral ranges, and high stability, which make them usable for biosensing, drug delivery, and therapeutics (Fig 1). In tissue engineering, chiral inorganic nanomaterials can control cell fate, increase scaffold bioactivity, and induce tissue-specific regeneration. For example, chiral AuNPs have exhibited enantioselective effects on cell adhesion and differentiation, and chiral QDs have been investigated for imaging and targeted therapy.^4,5

Nanomaterial chirality is a lack of mirror symmetry at the nanoscale, resulting in the existence of enantiomeric forms of left- and right-handed morphologies and distinct physical and chemical properties. Chiral nanomaterials exhibit chiroptic activity in the form of optical rotatory dispersion (ORD) and circular dichroism (CD) effects due to differential interaction with circularly polarized light (CPL).^6–8

FIG. 1.

Diagrammatic representation of chirality evolution from biological systems to therapeutic applications.

The current review discusses synthesis and characterization of chiral inorganic nanomaterials to their enantioselective interactions with cell constituents and application in scaffolding design for the regeneration of hard and soft tissues. Some examples such as modulation of cellular behavior, enantioselective catalysis, and drug delivery are explained, and some of the issues such as scalability, biocompatibility, and clinical translation are also discussed.¹

Chiral inorganic nanomaterials classification

Three general categories of nanomaterials according to material composition are metallic, semiconductor, and ceramic (Table 1).

Table 1.

Classification of Chiral Inorganic Nanomaterials

Material type	Examples	Key properties	Tissue engineering applications
Metallic	Gold (Au), silver (Ag), platinum (Pt) nanoparticles	Plasmonic activity, high chiroptical response, biocompatibility	Scaffolds for cell adhesion and growth, stem cell differentiation, photothermal drug delivery, imaging
Semiconductor	Cadmium sulfide (CdS), cadmium selenide (CdSe), copper sulfide (Cu_2-xS) quantum dots	Tunable optical properties, circular dichroism, circularly polarized luminescence	Biosensing, imaging, controlled drug release, bioactive scaffolds for hard/soft tissue regeneration
Ceramic	Cobalt oxide (Co₃O₄), hydroxyapatite nanoparticles	Mechanical strength, biocompatibility, chiroptical activity in UV-visible range	Bone tissue scaffolds, osteoblast differentiation, bone regeneration

Metallic chiral nanomaterials

Metallic chiral nanomaterials such as gold (Au), silver (Ag), and platinum (Pt) NPs are widely studied for their plasmonic and high chiroptical activity based on chirality induced by surface ligands or intrinsic lattice distortion. AuNPs, for example, can be prepared with chiral morphologies by employing chiral ligands like L- or D-cysteine, resulting in enantioselective recognition of cells and biomolecules.^3,9

Semiconductor chiral nanomaterials

Semiconductor-derived chiral nanomaterials, such as cadmium sulfide (CdS), cadmium selenide (CdSe), and copper sulfide (Cu_2-xS) QDs, are distinguished by chirality through lattice deformations or by functionalization with chiral ligands. They are characterized by their tunable optical properties, including CD and CPL, necessary for biosensing and imaging in tissue engineering.⁶ For instance, chiral CdSe/CdS QDs have been employed to monitor cellular processes due to their enantioselective binding with chiral biomolecules, thus facilitating the construction of bioactive scaffolds. Also, penicillamine-derived chiral Cu_2-xS QDs are photocatalytic under the action of CPL, and they can be utilized for drug-controlled release in tissue repair.¹⁰

Ceramic chiral nanomaterials

Chiral ceramic nanomaterials such as chiral cobalt oxide (Co₃O₄) and hydroxyapatite (HAP) NPs are of considerable importance for their mechanical strength as well as their biocompatibility, and hence they find application in bone tissue engineering. NPs of chiral cobalt oxide, synthesized from chiral peptides such as Tyr–Tyr–Cys, possess intense chiroptical properties in the UV–visible region, and hence they find application in being incorporated in scaffolds that favor the differentiation of osteoblasts.¹¹ Chiral HAP thin films have been shown to possess enantioselective interaction of cell structure, thereby enhancing bone regeneration by replicating the chiral structure of the natural bone matrix.³

Comparative analysis with organic chiral nanomaterials

Chiral nanomaterials, whether inorganic or organic, play a pivotal role in tissue engineering due to their ability to mimic the stereospecific interactions of biological systems. Chiral nanomaterials that are inorganic, such as Au, silica, and cobalt oxide NPs, will behave much differently than chiral nanomaterials made of organic matters, which can be chiral carbon dots or polymeric scaffolds. Chiral nanomaterials that are inorganic, such as gold, silica, and cobalt oxide NPs, will perform differently from chiral nanomaterials made of organic matter, which are chiral carbon dots or polymeric scaffolds. Organic chiral nanomaterials also have the biomimicry and biocompatibility benefits of being closer to the molecular structures of biological systems than inorganic chiral nanomaterials are. Therefore, a side-by-side comparison of these chiral nanomaterials is important to evaluate their respective merits and shortcomings. Table 2 provides a comparison of inorganic chiral nanomaterials to organic chiral nanomaterials including characteristics, synthesized representations, biological interactions, and tissue engineering applications.

Table 2.

Comparison of Inorganic and Organic Chiral Nanomaterials in Tissue Engineering

Parameter	Inorganic chiral nanomaterials	Organic chiral nanomaterials	Implications for tissue engineering	References
Material examples	Gold (Au), silver (Ag), cobalt oxide (Co₃O₄), silica (SiO₂), cadmium selenide (CdSe) nanoparticles	Chiral carbon dots, chiral polymers (e.g., poly-L-lactic acid), peptide-based scaffolds	Inorganic materials suit mechanically demanding applications; organic materials excel in biomimicry.	^3,9
Chiroptical properties	High dissymmetry factors (g-factors up to 0.1–2), strong circular dichroism (CD) and optical rotatory dispersion (ORD) responses	Lower g-factors (10⁻⁴ to 10⁻³), CD/ORD signals closer to biomolecules	Inorganic nanomaterials enable sensitive biosensing and imaging; organic nanomaterials align with biological chirality.	^12,13
Mechanical stability	High thermal and chemical stability, resistant to degradation in physiological environments	Prone to degradation under physiological conditions, limited mechanical strength	Inorganic materials are ideal for load-bearing scaffolds (e.g., bone); organic materials suit soft tissue applications.	^14,15
Biocompatibility	Good biocompatibility with chiral ligand modification, potential for long-term stability but requires careful surface engineering	High biocompatibility due to molecular similarity to biological systems, minimal immune response	Organic nanomaterials integrate seamlessly with soft tissues; inorganic materials need optimization for long-term use.	^4,16
Enantioselective interactions	Strong stereospecific interactions with cells and biomolecules, enabling precise control of cellular fate	Moderate enantioselective interactions, closely mimicking natural ECM chirality	Inorganic materials excel in directing stem cell differentiation; organic materials support natural cellular processes.	^5,17,18
Applications	Bone regeneration (e.g., chiral hydroxyapatite), neural repair, drug delivery, biosensing	Soft tissue regeneration (e.g., vascular, skin), drug delivery, fluorescence imaging	Inorganic materials are versatile for hard tissues and imaging; organic materials are preferred for soft tissues.	^1,15
Scalability	High production costs, complex synthesis limits scalability	Cost-effective, scalable synthesis due to simpler molecular assembly	Organic nanomaterials are more feasible for large-scale clinical applications.	^5,19
Limitations	Challenges in achieving consistent chirality, potential toxicity, regulatory hurdles	Limited mechanical strength, degradation in vivo, lower chiroptical response	Inorganic materials face translational barriers; organic materials are limited by durability.	^13,20

ECM, extracellular matrix.

Mechanisms of Chirality Induction

Chirality in inorganic nanomaterials can be induced by various mechanisms, which apply different physical, chemical, or biological principles to incorporate handedness. Understanding these mechanisms is relevant for the synthesis of nanomaterials with a desired set of chiroptical and biological characteristics for tissue engineering.

Biomolecule-driven induction

The chirality of the biomolecules, such as amino acids, peptides, and nucleic acids, can be used as chiral ligands/templates to develop chiral nanomaterials from inorganic nanomaterials. For instance, the conjugation of L/D-amino acids with AuNPs approves the enantioselective cell or protein interactions, which is very essential in the building of tissue engineering scaffold.²¹ Peptide bonds’ hydrogen bonding and chiral centers of the protein molecules control torsional twist of the organometallic moieties in order to obtain helical chirality in the ferrocene–dipeptide conjugates.²²

Light-mediated induction

Helical electric field that characterizes CPL allows it to have specific interaction with achiral precursors creating chiral structures.²³ For example, in this method, the enantioselective polymerization can be achieved simply by irradiating CPL of 980 nm in sodium yttrium fluoride up conversion NPs, thus giving chiral polymer chains of optimized handedness.^24,25

Template-based and structural induction

Chiral template or catalyst-directed synthesis of chiral nanomaterial is the structural induction. For example, chiral covalent organic frameworks can form from the utilization of (R)- or (S)−1-phenylethylamine as a chiral catalyst to deliver homochiral structures of a propeller-type conformation.²⁶ The same way, inorganic nanomaterials, for instance, CdTe QDs could be chiral if they are synthesized using chiral ligands or templates.^27,28

Synthesis and Characterization of Chiral Inorganic Nanomaterials

Synthesis routes

Chiral inorganic nanomaterials could be produced through numerous top-down or bottom-up methods, which each carry different strengths and weaknesses as described below (Table 3). Direct comparisons between all these different methods in a quantitative sense with yield, cost, reproducibility, and scalability are very important to enable their practical use in tissue engineering and beyond. As another example, bottom-up approaches such as wet-chemical synthesis can encompass high-yielding (e.g., 80.95% yield on chiral AuNPs) synthesis but use chiral ligands that incur a high cost and thus are difficult to scale.^29,30 In contrast, the top-down methods, such as the electron beam lithography (EBL) provide good reproducibility and scalability to industry; however, they are more expensive to perform, have lower yield (e.g. 50.70% of chiral nanohole arrays) because material is lost during the fabrication process carried out.^31,32 This trade-off is restated in Table 3 to inform selection of methods depending on its practicability.

Table 3.

Various Synthetic Approaches to Create Chiral Inorganic Nanomaterials

Synthesis method	Technique	Description	Tissue engineering relevance	Yield (%)	Cost	Reproducibility	Scalability	Reference
Bottom-Up	Wet-chemical synthesis	Uses chiral ligands (e.g., L-/D-glutathione, cysteine) to induce chirality in nanoparticles such as AuNPs or CdTe quantum dots	Produces biocompatible chiral nanoparticles for scaffolds, mimicking ECM chirality for cell adhesion and differentiation	80–95	High (due to chiral ligands)	Moderate (ligand-dependent)	Low (batch processing)	^29,30
Bottom-Up	Self-assembly	Employs noncovalent interactions or CPL to form chiral superstructures (e.g., CdTe nanoribbons, Ag NP helices)	Creates biomimetic chiral nanostructures for 3D-printed scaffolds, enhancing tissue regeneration without toxic reagents	70–90	Moderate (reagent-dependent)	High (for simple superstructures)	Moderate (automation potential)	³
Top-Down	Lithography (e.g., electron beam, nanosphere)	Patterns chiral metasurfaces or nanohole arrays on substrates using masks or etching	Fabricates large-area chiral surfaces for scaffolds, guiding cell alignment in bone or vascular tissue regeneration	50–70	High (equipment costs)	High (precise patterning)	High (industrial compatibility)	³¹
Top-Down	Etching (e.g., reactive ion, wet chemical)	Selectively etches chiral templates (e.g., silica molds) to form chiral nanoparticles such as Au helicoids	Produces chiral nanoparticles for porous scaffolds, supporting soft tissue regeneration with precise cell alignment	60–80	Low (cost-effective materials)	Moderate (mask variability)	High (large-area patterning)	³²
Chiral Templates/Ligands	Biomolecule ligands (e.g., cysteine, peptides)	Induces chirality via surface binding or lattice distortion in nanoparticles such as Co₃O₄	Enhances scaffold biocompatibility, supports chondrocyte/neural cell differentiation	75–90	Moderate (template fabrication)	High (template-controlled)	Moderate (template reusability)	³³

Bottom-up methods (wet-chemical, self-assembly)

Bottom-up synthesis techniques synthesize chiral inorganic nanomaterials from atomic or molecular building blocks, providing size, shape, and chirality control in precise detail, which are essential for tissue engineering. Wet-chemical synthesis is a basic technique, employing chiral ligands to impose enantioselective growth. Chiral AuNPs, for instance, are synthesized through gold salt reduction with chiral thiols like L- or D-glutathione achieving yields of 80–95% under optimized conditions.^29,30 However, the high cost of chiral ligands (e.g., glutathione at $100–200/g) and batch-to-batch variability can limit scalability and reproducibility.²⁹ They can embed these chiral QDs in hydrogels to construct stem cell differentiation scaffolds used to recreate complex tissues such as cartilage tissue or neuronal tissue. These chiral QDs can be cast into hydrogels to create scaffolds that guide stem cell differentiation, necessary to regrow complex tissues such as cartilage or neural tissue.

Self-assembly, another bottom-up approach, organizes NPs into chiral superstructures via noncovalent interactions, with yields typically ranging from 70–90% depending on the system.³ CPL is an advanced technique for creating chirality in nanoparticle dispersions. This photoinduced process is useful for tissue engineering because it does not use noxious reagents, providing nontoxic biocompatible chiral nanostructures, which can be filled into 3D-printed scaffolds for optimizing tissue regeneration. Just as peptide-directed self-assembly of metal NPs (such as Ag NPs) also forms helical superlattice, depicting the chiral morphology of collagen and transporting scaffold bioactivity for promoting bone or skin regeneration.³

Top-down techniques (lithography, etching)

Top-down approaches build chiral nanomaterials by converting bulk materials into nanoscale geometries through advanced micro and nanofabrication techniques, thus obtaining scalability and reproducibility for tissue engineering. EBL is widely utilized to pattern chiral plasmonic meta-surfaces.³¹ Nanosphere lithography is a cost-effective alternative, which utilizes self-assembled polystyrene spheres as masks to pattern chiral nanohole arrays on silicon or metal substrates with yields of 60–80% and lower costs ($10,000–100,000 for equipment) but moderate reproducibility due to mask variability.³² Ha et al. synthesized chiral Au helicoids by selectively etching metal films from chiral silica templates to form NPs with strong CD signals in the visible region.³³

The chiral template and ligand role

Chiral biomolecules, for example, amino acids (e.g., L-/D-cysteine and penicillamine) or peptides, serve as ligands that bind to the surface of NPs, and chirality is introduced via asymmetrical interactions at the surface or lattice distortions. Co₃ O₄ NPs coated with L- and D-cysteine show yields of 75–85% and high reproduction in controlled synthesis conditions.¹⁹ These NPs may be integrated with hydrogels to form chiral microenvironment and preferentially promote those chondrocyte or neural cell differentiation of nerve or cartilage regeneration. Large-scale production is, however, possible due to the cost of chiral ligands (cost of e.g., cysteine is $50–100/g).¹⁹ Li et al. observed enantioselective rearrangement of cysteine-derived chiral carbon dots-supercoiled DNA, which showed 80–90% yields and moderate scalability by virtue of the wet-chemical methodology (Fig 2).³⁴

FIG. 2.

Schematic representation of the enantioselective topological rearrangement of supercoiled DNA utilizing chiral carbon dots.

Chiral templates, such as silica molds or polymer scaffolds, provide enclosed environments for the synthesis of intricate chiral nanostructures. Ha et al. successfully employed chiral silica molds, which were produced through etching chiral Au helicoids, to synthesize Ag, Pd, and Pt helicoids with preserved chirality.³³ Metallic helicoids from these metals are prospective candidates for tissue engineering due to their antibacterial properties and enantioselective interactions. Noncontact templates, such as CPL, are also significant. Cho et al. demonstrated that CdTe NPs can be ordered by CPL into helical assemblies, yielding chiral nanostructures in the absence of physical templates.³

Characterization methods

Chiroptical analysis (CD, ORD)

Chiroptical techniques, that is, ORD and CD, are crucial in assessing the optical activity of chiral inorganic nanomaterials and their suitability for application in tissue engineering. CD measures quantitatively the differential absorption of right- and left-handed circularly polarized light and provides information on chirality. Chiral Au nanooctopods, for example, fabricated from L- or D-glutathione, display mirror-image CD spectra reflecting their enantiomorphic feature and enantioselective interaction capacity toward ECM proteins.^29,35

Structural analysis (TEM, SEM, X-ray diffraction)

In order to validate the exploitation of chiral inorganic nanomaterials, precise information related to their morphology, dimensions, and other crystallographic characteristics is required. Hence, specific structural characterization procedures are essential to assure their application in tissue engineering scaffolds. In tissue engineering, TEM is also very vital in order to confirm the retention in structural integrity of chiral NPs after they are applied on scaffolds, thus justify the homogenous cellular interaction. Similarly, various scanning electron microscopy (SEM), enable the analysis in respect to the surface morphology, for example, homogeneity of chiral gold nanoplate arrays prepared by lithography.^30,31

Quantitative chirality analysis (3D electron tomography)

3D electron tomography is particularly helpful for complex chiral morphologies, such as twisted or helical NP assemblies, hard to detect by 2D imaging. For instance, 3D TEM tomography of CPL-induced CdTe NPs ascertains their helical nanoribbon morphologies with parameters being pitch, twist angle.¹⁴ 3D electron tomography in tissue engineering confirms the chiral nanomaterial is holding the target chirality in scaffolds, and this is essential in enantioselective cell signal and tissue regeneration.³³

Properties of Chiral Inorganic Nanomaterials in Alignment to the Tissue Engineering (Continued)

Chiral inorganic nanomaterials, characterized by their nonsuperimposable mirror-image structure, have unique properties that make them attractive candidates for tissue engineering. Some of these are chiroptical responses, enantioselective interactions, mechanical stability, and biocompatibility, each of which supports the accurate control of cellular behavior and mechanisms during tissue regeneration³⁶ (Table 4 and Fig. 3).

Table 4.

Properties of Chiral Inorganic Nanomaterials for Tissue Engineering

Property	Description	Tissue engineering implications
Chiroptical	Exhibits circular dichroism and optical rotatory dispersion, responding differently to left/right-handed CPL	Enables biosensing, real-time monitoring of regeneration, and photodynamic therapy for targeted tissue repair
Enantioselective Interactions	Stereospecific binding with biomolecules and cells, dependent on chirality (e.g., L-/D-coated NPs)	Guides stem cell differentiation, enhances cell adhesion, reduces immune responses in scaffolds
Mechanical/Structural	High stability, unique morphologies (e.g., helicoids, nanoribbons), high surface-to-volume ratio	Provides durable, biomimetic scaffolds for load-bearing tissues like bone, supports cell infiltration
Antibacterial/Biocompatibility	Selective antibacterial activity, low toxicity, minimal immune response	Reduces infection risk in scaffolds, enhances biocompatibility for long-term tissue integration

CPL, circularly polarized light; NPs, nanoparticles.

FIG. 3.

Unique chiral properties of inorganic nanomaterials.

Chiroptical properties and their biological implications

Chiroptical properties in tissue engineering facilitate sensitive biosensing and real-time monitoring of biological processes. The intense CD signals of chiral NPs can be utilized to detect chiral biomolecules, such as proteins or nucleic acids, with high selectivity, allowing for the identification of biomarkers related to tissue regeneration.³⁷ These aspects highlight the potential of chiroptical nanomaterials in diagnostic and therapeutic applications in tissue engineering.³⁸

Enantioselective cell and biomolecule interactions

Chiral NPs, such as L- or D-amino acid-coated NPs, have handedness-dependent biomolecule binding to proteins and DNA, affecting cellular uptake, adhesion, and signaling. The above interactions are especially significant for cellular fate control in tissue scaffolds. Chiral nanomaterials have the potential of influencing the direction of stem cell differentiation by mimicking the chiral ECM, thus providing the opportunity for lineage commitment to specific lineages.³⁹

Mechanical and structural properties

Inorganic chiral nanomaterials are distinguished by their improved mechanical and structural properties, which are desirable for tissue engineering scaffolds. The chiral lattice structures, typically synthesized with biomolecule templates or circularly polarized light, lead to unique morphological features, such as helicoids or twisted nanoribbons, that improve mechanical strength and porosity, allowing cell infiltration.⁴⁰ These morphological characteristics enable the creation of scaffolds that are biomimetic of the mechanical properties of the original tissue.^14,25,41

Antibacterial and biocompatibility properties

Enantioselective interactions enable chiral NPs to have selective antibacterial activities, which affect the bacterial membranes without affecting the mammalian cells. Additionally, chiral inorganic nanomaterials, especially those ligand-modified with biocompatible ligands such as peptides, are less toxic to cells and induce minimal immune response. Their chiral selectivity in their interactions with chiral biomolecules reduces nonspecific adsorption, thus enhancing biocompatibility.

Application in Tissue Engineering

Chiral inorganic nanomaterials, with their superior optical, chemical, and biological properties, have emerged as new tools for functional organ and tissue regeneration. These materials leverage enantioselective interactions, high biocompatibility, and tunable properties to resolve challenges in scaffold design, control of cell behavior, catalysis of tissue healing, and drug delivery and imaging⁴² (Table 5, Fig. 4 and Fig. 5).

Table 5.

Applications of Chiral Inorganic Nanomaterials in Tissue Engineering

Application	Description	Examples	Outcomes
Scaffold design (soft tissue)	Chiral scaffolds mimic ECM chirality for vascular, nerve, skin regeneration	D/L-phenylalanine-PCL scaffolds, L-CNC films, L-amino acid hydrogels	Enhanced endothelial cell adhesion, improved nerve conduction, faster fibroblast invasion
Scaffold design (hard tissue)	Chiral scaffolds promote osteogenesis for bone regeneration	L-CMHAP@CL scaffolds, chiral Co₃O₄ NPs, alginate-stabilized AuNPs	Increased bone formation, enhanced osteoblast differentiation, high biocompatibility
Cell regulation	Modulates adhesion, proliferation, differentiation via chiral interactions	L-penicillamine AuNP films, GLAD chiral scaffolds, dextral microcircle arrays	Faster cell proliferation, directed neural stem cell differentiation, activated osteogenic pathways
Enantioselective catalysis	Catalyzes chiral biomolecule synthesis for tissue repair	Chiral SiO₂, Fe₃O₄ NPs, ZnS supraparticles	Enhanced cell adhesion/proliferation, improved neural/bone tissue repair, high enantioselectivity
Drug delivery/imaging	Enables targeted delivery and high-resolution imaging	Chiral AuNPs, plasmonic NPs, chiral carbon dots	Enantioselective drug release, enhanced imaging contrast, real-time regeneration monitoring

AuNPs, gold nanoparticles; ECM, extracellular matrix; GLAD, glancing angle deposition; NPs, nanoparticles; CMHAP, Chiral Mesostructured HydroxyAPatite; CNC, cellulose nanocrystals; PCL, poly(ε-caprolactone).

FIG. 4.

Diagram of illustrating multifunctional applications of chiral inorganic nanomaterials revolutionize tissue engineering through targeted regeneration, immune modulation, and precision therapy.

FIG. 5.

Tissue engineering applications of inorganic chiral nanomaterials.

Chiral nanomaterials in scaffold design

Chiral scaffolds can selectively interact with cells by enantioselective interactions, thus influencing processes such as mechanotransduction, integrin signaling, and gene expression.^8,16,43

Chiral scaffolds for soft tissue regeneration

Biological heterogeneity of chiral nanomaterial responses between various cell types and tissue microenvironments necessitates deep in vivo studies, which are not yet available.⁴ In tissue engineering, in which cellular fate must be controlled stringently, these translational problems turn into impediments to developing effective therapeutic interventions. Sun et al. (2018) performed a preclinical study, in which they used chiral AuNPs coated with L-cysteine in the targeted repair of neural tissue using a hydrogel scaffold.⁴⁴ When compared with achiral controls, the motor functional recovery was also found to have been improved by 20% at week 8 owing to the neuronal stem differentiation and axonal organization of the L-cysteine functionalized AuNP scaffold on a rat model of spinal cord injury. This can be used to emphasize enantioselective reactions of chiral nanomaterials with cell nerve cells leading to a promotion of repair in soft tissues.⁴⁴

Chiral scaffolds for hard tissue (bone) regeneration

Chiral inorganic nanomaterials have also been used widely in the regeneration of hard tissues, including bone tissue engineering, where bioadaptivity to the scaffold and osteogenesis are of key importance. In vivo experiments proved that L-CMHAP@CL scaffolds, prepared with L-tartaric acid, greatly improved angiogenesis and osteogenesis relative to D-CMHAP@CL or achiral scaffolds. The L-CMHAP@CL scaffolds showed enhanced bone formation, evidenced by higher values of integrated optical density (IOD/area of 0.25 compared with 0.20–0.24 for D- and achiral scaffolds) and histological measurements after 24 weeks.¹¹ Another preclinical study led by Yang et al. (2025) also investigated chiral HAP NPs added to collagen scaffolds on bone regeneration in a rabbit model of the femur defect. The HAP scaffolding modified with L-tartaric acid recorded the highest enhanced osteoblast propagation and enhancement in bone mineral density of 30% after 12 weeks, compared to those modified with D-tartaric acid or achiral at the end of 12 weeks.⁴⁵

Besides, chiral cobalt oxide nanoparticles L- and D-Tyr-Tyr-Cys ligand-functionalized have been employed in the development of scaffolds with superior chiroptical activity, hence promoting osteoblast differentiation through enhanced biochemical interactions.⁴² The inherent chirality of such scaffolds influences intracellular signaling pathways, for example, p38/mitogen-activated protein kinase (MAPK), that control stem cell fate toward osteogenic lineages.^29,46

Regulation of cell activity (adhesion, proliferation, differentiation)

Chiral materials with their nonsuperimposable mirror-image conformation interact stereospecifically with biological systems, thus regulating cellular outcomes by multiple mechanisms such as modulation of adhesion receptors, intracellular signaling pathways, and gene expression profiles.¹⁷ For instance, thin films of L- or D-penicillamine-functionalized chiral AuNPs have been demonstrated to yield different cellular behavior in terms of proliferation, wherein L-penicillamine thin films support the growth of cells faster than those of their D-counterparts, thus highlighting the importance of chirality in controlling cell-material interaction.^44,47 Similarly, chiral scaffolds, for example, those using glancing angle deposition, have been reported to direct selectively differentiation of neural stem cells, thus promising great use in the repair of neurological diseases.¹ It has also been shown that chiral geometries, for example, dextral microcircle arrays, trigger adhesion, and differentiation of human mesenchymal stem cells via activation of distinctive signaling pathways like p38/MAPK, thus highlighting the importance of chirality in governing stem cell direction.⁴⁶

Enantioselective catalysis to tissue repair

Inorganic chiral nanomaterials are a revolutionary paradigm in tissue engineering and have received attention based on their capability to induce enantioselective catalysis that can be tailored for application in tissue regeneration.^28,48

Tetrahedral SiO₄ units-bearing chiral silica (SiO₂) nanomaterials as a solid support for enantioselective catalysis can be designed to inherit chirality from organic templates and thus facilitate the synthesis of chiral biomolecules to support cell adhesion and proliferation towards tissue repair.⁴⁹ In addition, chiral metal oxide NPs such as poly(amino acid)-modified Fe₃O₄ have been found to show an enantioselective catalytic activity.⁵⁰

In tissue regeneration, the enantioselective activities of these nanomaterials are more concerned about the regulation of cellular function. These chiral nanomaterials engage with cells and biomolecules to regulate adhesion receptors, intracellular signaling pathways, and gene expression, factors critical for the regulation of stem cell differentiation and tissue repair.^51,52 Chiral HAP modifies enantioselective implant-bone interaction toward controlling osseointegration and for assisting bone tissue repair for treatment of osteoporosis.⁴⁵

Inorganic chiral nanomaterials are synthesized for enantioselective catalysis via chiral ligand-supported synthesis, chiral molecule-directed postmodification, or chiral template-controlled in situ synthesis.^28,53 Recently, 3D chirality recognition cavities can be generated in the supraparticles of self-assembled ZnS, thus overcoming these limitations as demonstrated by enhanced catalytic activity and enantioselectivity.²⁸

Chiral inorganic nanomaterials for drug delivery and imaging applications for tissue engineering

Inorganic chiral nanomaterials such as chiral metal NPs, semiconductors, and carbon nanostructures possess enantioselective interactions that maximize their performance in biological systems (Fig. 6).¹ In drug delivery, stereospecific interactions between chiral nanomaterials and biomolecules maximize targeted delivery and therapeutic performance. For instance, chiral AuNPs with chiral ligand modification have been shown to maximize cellular uptake and enable enantioselective drug release, a function that is very crucial for accurate tissue regeneration.⁵⁴ Chen et al. (2023) conducted a preclinical study of chiral SiO₂ NPs as drug carriers of intestinal tissue repair in a mouse model setting.⁵⁴ The enantioselectivity of the L-penicillamine-functionalized SiO₂ NPs in interacting with intestinal mucosa increased the oral adsorption of insoluble drugs by 25% over the D-penicillamine- functionalized NPs and tissue repair in investigated models of inflammatory bowel disease.

FIG. 6.

Diagnostic and therapeutic applications of chiral inorganic nanomaterials.

In imaging, inorganic chiral nanomaterials utilize their robust CD and CPL to offer high-resolution bioimaging. Chiral plasmonic NPs, such as those of gold or silver, offer improved contrast in imaging modalities such as fluorescence and photoacoustic imaging to facilitate real-time monitoring of tissue regeneration processes.⁴ Hou et al. (2020) conducted a preclinical experiment in an Alzheimer’s mouse model where they imaged the mice using a chiral AuNP. The AuNPs with the L-cysteine coating demonstrated enantioselective binding to amyloid-beta plaques, which made the high-point photoacoustic imaging performed with them exhibit 15% increase in contrast as compared with the achiral NPs due to their ability to compensate their usage in the real-time monitoring of the tissue regeneration.⁵²

Their catalytic activity is also exploited to replicate enzymatic activity for the purpose of triggering cell proliferation and differentiation. Chiral cobalt oxide NPs, for example, have been reported to induce osteogenesis by selectively stimulating bone cells for scaffold-guided regeneration of tissue.¹

Challenges and Limitations

One of the biggest challenges of synthesizing inorganic chiral nanomaterials is the accurate control of chirality in synthesis.²⁰ In tissue engineering, where chiral recognition is needed to guide stem cell differentiation or perform tissue-specific functions, inconsistent chirality can lead to uncontrollable biological responses.²⁸

Another limitation is related to the characterization of chiral nanomaterials at the nanoscale and the molecular length scales. While techniques such as CD spectroscopy and electron microscopy are helpful in collecting information about chiral properties, identifying the exact mechanisms by which chirality is transferred from organic templates or ligands to inorganic frameworks is a major challenge.^3,19

The majority of the synthesis pathways, including those involving chiral biomolecules or complex lithographic methods, are accompanied by high cost and prolonged times, making large-scale production economically unfeasible.⁵

Chiral inorganic nanomaterials such as gold, cobalt oxide, and silica NPs exhibit promise of biocompatibility, but their long-term stability and safety in biological systems remain to be explored in their entirety. Nanomaterials, in tissue engineering, must be stable in their chirality and structural integrity under physiological conditions without eliciting unwanted immune responses or toxicity.⁴

The existing literature indicates that in vitro research shows good levels of biocompatibility of chiral nanomaterials, such as AuNP surfaces covered with biocompatible ligands, yet substantial in vivo data are lacking to confirm that these results are true. As an example, there have been studies into chiral AuNPs, which have revealed minimal cytotoxicity in cell studies, although little is known about their long-term in vivo behavior, especially in relation to biodistribution, clearance, and the possibility of chronic effects and immune activation.⁵⁵ Likewise, the chiral silica NPs have also demonstrated some potential in drug delivery because of the enantioselective interaction, but the long-term safety including a possible tissue or organ accumulation has not been investigated.⁵⁶ That discrepancy in in vivo data falsifies their translational value because unexpected interactions with complex physiological environments may cause negative effects, for example, inflammation or organ dysfunction. Long-term in vivo research is essential to determine the capacity of these nanomaterials to maintain chiral properties under normal biological conditions as well as to scrutinize whether these nanomaterials will directly trigger unwanted immune interactions or toxicity with time.⁵⁷

The clinical translation of chiral nanomaterials is also faced with the severe challenges of regulatory and ethical concerns in tissue engineering. Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), demand strict safety and efficacy data; these are absent at present since use of chiral nanomaterials is still new. These materials have no standardized protocols of synthesis, characterization and preclinical testing, making it complex to have such medical devices or diagnostic therapies passed through the regulatory processes. Ethical considerations are possible health complications in people due to accumulating nanomaterials in the body over a long period, which may come with unknown adverse health impacts, and the necessity of granting equitable access to such advanced therapies, lest resulting in health care disparities. To deal with these problems, the development of interdisciplinary knowledge will be essential in providing a clear set of regulatory standards and frameworks of ethical conduct to help keep patients out of harm and society at large.⁵⁸

The clinical translation of chiral nanomaterials is also faced with the severe challenges of regulatory and ethical concerns in tissue engineering. Regulatory agencies, including the U.S. FDA and the EMA, demand strict safety and efficacy data; these are absent at present since the use of chiral nanomaterials is still new. These materials have no standardized protocols of synthesis, characterization and preclinical testing, making it complex to have such medical devices or diagnostic therapies passed through the regulatory processes. Ethical considerations are possible health complications in people due to accumulating nanomaterials in the body over a long period, which may come with unknown adverse health impacts, and the necessity of granting equitable access to such advanced therapies, lest resulting in health care disparities. To deal with these problems, the development of interdisciplinary knowledge will be essential in providing a clear set of regulatory standards and frameworks of ethical conduct to help keep patients out of harm and society at large.

The chiral nanomaterials do not have standardized methods of synthesis and characterization making them unrecognizable as a medical device and difficult to obtain clinical approval. In addition, the biological heterogeneity of chiral nanomaterial interactions due to cellular variation and tissue microenvironments requires extensive in vivo studies, which have yet to be done.⁴ Challenges to translational research are even more prevalent in tissue engineering, where cellular behavior must be tightly controlled.

Future Prospects

The application of chiral inorganic nanomaterials for tissue engineering stands at the precipice of gigantic strides, with the push arising from progress through synthesis, coordination with frontier technologies, and transdisciplinary.

Advanced synthesis and chirality control

New methods, such as Machine Learning (ML)-augmented synthesis and high-throughput screening automation, should be able to provide atomic-level control over chirality by 2030 to potentially enable the fabrication of nanomaterials with consistent handedness and characterized functionality.⁵ As another example, ML algorithms can be used to model optimal chances of synthesis of chiral AuNPs, and this can improve their selective associations with the biological systems.⁵⁹ Research is also in progress to develop bioinspired or biomimetic methods to achieve cost-effective and environmental friendly chiral nanomaterials, where natural phenomenon such as mollusk shell formation is being used. It is reasonable to expect that these approaches will be commercially scalable within 10 years and increase the availability to clinical use.⁶⁰

Enhanced cellular interactions

The use of specific geometry nanomaterials such as the helical silica nanoparticle is currently being experimented on to facilitate the osteogenic differentiation of bone repair and the alignment of nerves. Research into the potential impact of chiral graphene oxide scaffold has shown that differentiation by mesenchymal stem cells after their exposure to the scaffold has occurred up to 25% faster than the achiral counterparts with potential clinical trials expected to take place in 2028.⁶¹ In the same way, carbon nanotubes that are chiral have demonstrated a possibility in directing the alignment of nerve cells and the speed of nerve repair procedures is likely to happen within 5–7 years.³⁴

Integration with 3D and 4D bioprinting

The use of chiral nanomaterials in 3D bioprinting is rapidly increasing, whereby chiral gold or silica NPs incorporated into hydrogels can recapitulate chiral cues of the extracellular environment and dictate the orientation of cells and directed cell differentiation. As an example, chiral silica NPs demonstrated an increase in the biofunctionality of a scaffold by 30%, in regard to cell adhesion and proliferation.⁶² With the introduction of 4D bioprinting, the structures formed are not set, but are formed over time, and will likely utilize the dynamic chirality under physiological conditions, that is, movement in pH or temperature, to allow the formation of adaptive tissues. By 2032, research groups are aiming at a functional 4D-printed chiral scaffold to be used in the soft tissue engineering process.

Personalized modeling and bioinformatics

There is also the need to develop patient-tailored modeling and advanced bioinformatics to enable the design of biocompatible chiral nanomaterials according to the immune profile of an individual patient. Computation platforms involving single-cell RNA sequencing in combination with molecular dynamics simulations will have the ability to predict nanomaterial-immune interactions with 90% accuracy and help to cut down adverse effects by 2035.⁶³ The future will be anchored in implementing algorithms to design chiral nanomaterial surface chemistry with an aim of facilitating its tailored tissue engineering applications.⁶⁴

Interdisciplinary collaboration between bioengineering, materials science, clinical research, and computational modeling is necessary to realize the full potential of chiral nanomaterials. Such areas of research are the standardization of protocols and measuring chiral nanomaterials by 2027 and regulatory standards of clinical translation in 2030. Combined efforts, including chiral nanomaterials in the context of gene editing-based neutropenias, are proposed to optimize the final result of tissue regenerations. These efforts are expected to yield breakthroughs in scalable, clinically viable applications within the next 10–15 years.

Conclusion

Advancements in synthesis and characterization technologies position chiral NPs as essential components of next-generation tissue engineering techniques. Key areas necessitating increased focus include the development of scalable and cost-effective synthesis protocols, the optimization of characterization protocols to elucidate chirality mechanisms, and the execution of comprehensive in vivo studies to assess long-term biocompatibility and efficacy. Translational studies must also be conducted to establish standardized methodologies and effectively navigate regulatory pathways for clinical translation. Interdisciplinary collaboration is essential to tackle these issues and to translate chiral nanomaterials from laboratory advancements to significant clinical applications.

Authors’ Contributions

All authors contributed equally with no competing interests.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funds received for this work.

References

Yang

, Jaiswal

, Yin

, et al. Chiral nanomaterials in tissue engineering. Nanoscale, 2024; 16(10):5014–5041.

Song

, Hao

, Li

, et al. Chiral inorganic nanomaterials in the tumor microenvironment: A new chapter in cancer therapy. Pharmacol Res, 2024; 208:107386.

Cho

, Guerrero-Martínez

, Ma

, et al. Bioinspired chiral inorganic nanomaterials. Nat Rev Bioeng, 2023; 1(2):88–106.

Wang

, Zhang

, Kuang

, et al. Chiral inorganic nanomaterials for bioapplications. Matter, 2023; 6(6):1752–1781.

Liu

, Yang

, Qin

, et al. Recent advances in inorganic chiral nanomaterials. Advanced Materials, 2021; 33(50):2005506.

, Xu

, de Moura

, et al. Chiral inorganic nanostructures. Chem Rev, 2017; 117(12):8041–8093.

Kwon

, Park

, Choi

, et al. Chiral spectroscopy of nanostructures. Acc Chem Res, 2023; 56(12):1359–1372.

Xiao

, An

, Wang

, et al. Novel properties and applications of chiral inorganic nanostructures. Nano Today, 2020; 30:100824.

Ditta

, Yaqub

, Tanvir

, et al. Gold nanoparticles capped with L-glycine, L-cystine, and L-tyrosine: Toxicity profiling and antioxidant potential. J Mater Sci, 2023; 58(6):2814–2837.

10.

Shao

, Yang

, Lin

, et al. Shining light on chiral inorganic nanomaterials for biological issues. Theranostics, 2021; 11(19):9262–9295.

11.

Fan

, Ren

, Ning

, et al. Enantioselective antiviral activities of chiral zinc oxide nanoparticles. ACS Appl Mater Interfaces, 2023; 15(50):58251–58259.

12.

Kotov

, Liz-Marzán

, Wang

. Chiral nanomaterials: Evolving rapidly from concepts to applications. Mater Adv, 2022; 3(9):3677–3679.

13.

Fan

, Ou‐yang

, Zhou

, et al. Biological applications of chiral inorganic nanomaterials. Chirality, 2022; 34(5):760–781.

14.

Alshammari

, Lashin

, Mahmood

, et al. Organic and inorganic nanomaterials: Fabrication, properties and applications. RSC Adv, 2023; 13(20):13735–13785.

15.

Wang

, Feng

. Chiral fiber supramolecular hydrogels for tissue engineering. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2023; 15(2):e1847; doi: 10.1002/wnan.1847

16.

Green

, Lee

, Kim

, et al. Chiral biomaterials: From molecular design to regenerative medicine. Adv Materials Inter, 2016; 3(6):1500411.

17.

Guo

, Guo

, Wang

, et al. Interface chirality: From biological effects to biomedical applications. Molecules, 2023; 28(15):5629.

18.

Zhao

, Zang

, Chen

. Stereospecific interactions between chiral inorganic nanomaterials and biological systems. Chem Soc Rev, 2020; 49(8):2481–2503.

19.

, Cölfen

. Chirality communications between inorganic and organic compounds. SmartMat, 2021; 2(1):17–32.

20.

, Xu

, Wang

, et al. Chirality‐based biosensors. Adv Funct Materials, 2019; 29(1):1805512.

21.

Yuan

, Ge

, Zhou

, Tang

. Size, composition, and surface capping-dependent catalytic activity of spherical gold nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc, 2023; 287(Pt 2):122082.

22.

Kovačević

, Roca

, Jadreško

, et al. Conformational, Electrochemical, and Antioxidative Properties of Conjugates of Different Ferrocene Turn-Inducing Scaffolds with Hydrophobic Amino Acids. Inorganics (Basel), 2024; 12(7):195.

23.

Cao

, Song

, Chan

, et al. Chiral perovskite nanoplatelets with tunable circularly polarized luminescence in the strong confinement regime. Adv Opt Mater, 2023; 11(12):2203125.

24.

Yang

, Zhang

, Hu

, Fujiki

, Zou

. The chirality induction and modulation of polymers by circularly polarized light. Symmetry (Basel), 2019; 11(4):474.

25.

Sun

, Hou

, Sun

, et al. Use of electrospun Phenylalanine/Poly-ε-Caprolactone chiral hybrid scaffolds to promote endothelial remodeling. Front Bioeng Biotechnol, 2021; 9:773635.

26.

Han

, Zhang

, Huang

, et al. Chiral induction in covalent organic frameworks. Nat Commun, 2018; 9(1):1294.

27.

Yang

, Dong

, Ren

. Chiral ligand‐induced photoluminescence intermittence difference of CdTe quantum dots. Luminescence, 2018; 33(7):1150–1156.

28.

, Xu

, et al. Emerging trends in chiral inorganic nanomaterials for enantioselective catalysis. Nat Commun, 2024; 15(1):3506.

29.

, Gao

, Zhang

, et al. Gold-nanoparticle-based chiral plasmonic nanostructures and their biomedical applications. Biosensors (Basel), 2022; 12(11):957.

30.

Yeom

, Santos

, Chekini

, et al. Chiromagnetic nanoparticles and gels. Science, 2018; 359(6373):309–314.

31.

Matassa

, Ray

, Zheng

. Chirality in nanomaterials. Sci Rep, 2024; 14(1):26268.

32.

, Pauly

. Chiral plasmonic nanostructures: Recent advances in their synthesis and applications. Mater Adv, 2022; 3(1):186–215.

33.

, Kim

, Han

, et al. Synthesis of chiral Ag, Pd, and Pt helicoids inside chiral silica mold. J Am Chem Soc, 2024; 146(45):30741–30747.

34.

Niu

, Liu

, Zhao

, et al. Chiral carbon nanostructures: A gateway to promising chiral materials. J Mater Chem A, 2024; 12(28):17073–17127.

35.

Kim

, Lee

, Han

, et al. Helicoid grating-coupled surface plasmon resonance sensor. Nano Lett, 2024; 24(49):15668–15675.

36.

, Qu

, Huang

XUE

, et al. Chiral Inorganic Nanomaterials for Biological Features. Acc Chem Res, 2025; 58(16):2613–2626; doi: 10.1021/acs.accounts.5c00364

37.

Pakki

, Goyal

, Chinmay

, et al. Chiral nanomaterials: Emerging therapeutics in the field of medicinal chemistry. J Mater Res, 2025; 40(7):981–1008; doi: 10.1557/s43578-025-01572-0

38.

Tan

, Fu

, Gao

, Wang

. Chiral plasmonic hybrid nanostructures: A gateway to advanced chiroptical materials. Advanced Materials, 2024; 36(3):2309033.

39.

Peng

, Yuan

, XuHong

, et al. Chiral nanomaterials for tumor therapy: Autophagy, apoptosis, and photothermal ablation. J Nanobiotechnology, 2021; 19(1):220–213.

40.

Jia

, Yang

, Du

, et al. Uncovering the recent progress of CNC‐Derived chirality nanomaterials: Structure and functions. Small, 2024; 20(35):2401664; doi: 10.1002/smll.202401664

41.

Chan

, Leong

. Scaffolding in tissue engineering: General approaches and tissue-specific considerations. Eur Spine J, 2008; 17(Suppl 4):467–479.

42.

Padmanabhan

, Kyriakides

. Nanomaterials, inflammation, and tissue engineering. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2015; 7(3):355–370.

43.

Gao

, Qin

. Organic chiral spin-optics: The interaction between spin and photon in organic chiral materials. Adv Opt Mater, 2021; 9(22):2101201.

44.

Sun

, Hao

, Li

, et al. Direct observation of selective autophagy induction in cells and tissues by self-assembled chiral nanodevice. Nat Commun, 2018; 9(1):4494.

45.

Yang

, Du

, Jin

, et al. Chirality‐Induced hydroxyapatite manipulates enantioselective bone‐implant interactions toward ameliorative osteoporotic osseointegration. Advanced Science, 2025; 12(8):2411602.

46.

Dong

, Gong

, Wang

, et al. Chiral geometry regulates stem cell fate and activity. Biomaterials, 2019; 222:119456.

47.

Bettini

, Ottolini

, Valli

, et al. Synthesis and characterization of gold chiral nanoparticles functionalized by a chiral drug. Nanomaterials (Basel), 2023; 13(9):1526.

48.

Guo

, Zhang

, Yang

, Sui

. Enhancing the mechanical strength of 3D printed GelMA for soft tissue engineering applications. Mater Today Bio, 2024; 24:100939; doi: 10.1016/j.mtbio.2023.100939

49.

Huang

, Zang

, Xu

, et al. Synthesis of chiral conjugated microporous polymer composite membrane and improvements in permeability and selectivity during enantioselective permeation. Sep Purif Technol, 2021; 266:118529.

50.

Hariani

, Said

, Rachmat

, et al. Preparation of NiFe₂O₄ nanoparticles by solution combustion method as photocatalyst of Congo red. Bull Chem React Eng Catal, 2021; 16(3):481–490.

51.

Wang

, Zhang

, Xie

, et al. Chiral engineered biomaterials: New frontiers in cellular fate regulation for regenerative medicine. Adv Funct Materials, 2025; 35(20):2419610; doi: 10.1002/adfm.202419610

52.

Hou

, Zhao

, Wang

, et al. Chiral gold nanoparticles enantioselectively rescue memory deficits in a mouse model of Alzheimer’s disease. Nat Commun, 2020; 11(1):4790.

53.

Kachtík

, Citterberg

, Bukvišová

, et al. Chiral nanoparticle chains on inorganic nanotube templates. Nano Lett, 2023; 23(13):6010–6017.

54.

Chen

, Cheng

, Pan

, et al. Chiral nanosilica drug delivery systems stereoselectively interacted with the intestinal mucosa to improve the oral adsorption of insoluble drugs. ACS Nano, 2023; 17(4):3705–3722.

55.

Shukla

, Bansal

, Chaudhary

, et al. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: A microscopic overview. Langmuir, 2005; 21(23):10644–10654.

56.

Nayl

, Abd-Elhamid

, Aly

, Bräse

. Recent progress in the applications of silica-based nanoparticles. RSC Adv, 2022; 12(22):13706–13726.

57.

Fadeel

, Farcal

, Hardy

, et al. Advanced tools for the safety assessment of nanomaterials. Nat Nanotechnol, 2018; 13(7):537–543.

58.

Wang

, Zhao

, Zhang

, et al. A journey of challenges and victories: A bibliometric worldview of nanomedicine since the 21st century. Advanced Materials, 2024; 36(15):2308915.

59.

Qiao

, Li

, Wang

, et al. Assembly-Dependent regulation of the chiroptical responses of chiral gold nanoparticles. ACS Nano, 2025; 19(29):26583–26591; doi: 10.1021/acsnano.5c05269

60.

Zuo

, Yang

, Zhang

, et al. Bioinspired multiscale mineralization: From fundamentals to potential applications. Macromol Biosci, 2024; 24(2):e2300348.

61.

Abd

, Díaz

, Gupta

, et al. Carbon nanomaterials‐based electrically conductive scaffolds for tissue engineering applications. MedComm–Biomaterials and Applications, 2024; 3(2):e76; doi: 10.1002/mba2.76

62.

Wang

, Li

, He

, et al. Multichiral mesoporous silica screws with chiral differential mucus penetration and mucosal adhesion for oral drug delivery. ACS Nano, 2024; 18(25):16166–16183.

63.

Mazumdar

, Khondakar

, Das

, et al. Artificial intelligence for personalized nanomedicine; from material selection to patient outcomes. Expert Opin Drug Deliv, 2025; 22(1):85–108.

64.

Skrna

, Kessler

, Liu

, et al. Reproduction of chiral anisotropy in surface-enhanced raman scattering on gold nanowires by computational modeling. J Phys Chem C, 2024; 128(30):12649–12656.