Exogenous genes are inserted into target cells during gene therapy in order to compensate or rectify disorders brought on by faulty or aberrant genes. However, gene therapy is still in its early stages because of its unsatisfactory therapeutic effects which are mainly due to low transfection efficiency of vectors, high toxicity, and poor target specificity. A natural polymer with numerous bioactive sites, good mechanical qualities, biodegradability, biocompatibility, and processability called silk fibroin has gained attention as a possible gene therapy vector. Using silk fibroin as a gene vector can reduce cell toxicity, extend the duration of gene expression, and allow further release even in the bloodstream, thereby expanding its therapeutic scope. This review outlines the advancements made with regard to gene delivery methods based on silk fibroin materials in the fields of malignant tumors, bone tissue regeneration, neural tissue, and vascular tissue engineering. Silk fibroin exhibits remarkable repair and therapeutic effects in gene therapy and can be employed in numerous forms, such as a vector (nanoparticles, microcapsules) or a matrix (hydrogel, scaffold) for gene delivery.

Through millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions. During in vivo degradation, this material primarily undergoes host cell-mediated surface degradation, rather than bulk hydrolysis. We demonstrate significant capabilities of CFSCs in promoting vascularization and macrophage differentiation toward repair. A bone defect model further indicates the potential of CFSC for bone graft applications. Our belief is that the material family of CFSCs may promise a novel biomaterial strategy for yet to be achieved excellent regenerative implants.

A mere glance at the foundation of the sericulture industry to produce silk and the consequent establishment of the Silk Road to transport it; elucidates the significant role that this material has played in human history. Owing to its exceptional robustness, silk was introduced into medicine as a surgical suture approximately two millennia ago. During the last decades, silk has garnered attention as a possible source of biological-based materials that can be effectively used in regenerative medicine. Silk's unique characteristics, like its low immunogenicity, suitable adhesive properties, exceptional tensile strength, perfect hemostatic properties, adequate permeability to oxygen and water, resistance to microbial colonization, and most importantly, excellent biodegradability; make it an outstanding choice for biomedical applications. Although there are many different types of silk in nature,Bombyx mori(B. mori) silk accounts for about 90% of global production and is the most thoroughly investigated and the most commonly used. Silk fibroin (SF) and silk sericin (SS) are the two main protein constituents of silk. SF has been manufactured in various morphologic forms (e.g. hydrogels, sponges, films, etc) and has been widely used in the biomedical field, especially as a scaffold in tissue engineering. Similarly, SS has demonstrated a vast potential as a suitable biomaterial in tissue engineering and regenerative medicine. Initial studies on SF and SS as wound dressings have shown encouraging results. This review aims to comprehensively discuss the potential role of silk proteins in refining wound healing and skin regeneration.

Silk fibroin (SF) is an extensively utilized biofiber recognized for its excellent mechanical properties across various applications. However, the relationship between its internal structure and mechanical behavior remains inadequately understood. In this work, we employed polarized Raman spectra to investigate how SF's secondary structures respond to external tensile loads. Our results show considerable variations in the amide III band, particularly the 1210 cm-1 random coil subpeak, under tensile stimuli. Subsequent loading-unloading experiments that plotted the peak intensity ratio of I1210 cm-1/I1226 cm-1 against tensile strain produced multiple hysteresis loops, suggesting irreversible structural changes during mechanical cycling. With additional evidence from other characteristic bands, we demonstrate that tensile elongation facilitates the transition of random coils to β-sheets within the SF network, which intrinsically contributes to the fiber's stiffening behavior. This work provides valuable insight into SF's deformation mechanism and highlights the significance of the previously underappreciated amide III band.

Gold nanorods (AuNRs) have shown great potential as photothermal agents for cancer therapy. However, the biosafety of AuNRs ordinarily synthesized using a cationic ligand assistance procedure has always been a subject of controversy, which limits their application in tumor therapy. In this study, we propose a novel strategy to enhance the biocompatibility of AuNRs by constructing a biological coating derived from silk fibroin (SF) on their surface. The SF coating could be easily and precisely manipulated using a layer-by-layer (LBL) assembly method. The resulting SF-coated gold nanorods (AuNRs@SF) exhibited reduced cytotoxicity and improved hemocompatibility compared to untreated AuNRs. Moreover, the treated nanorods were easily modified with a tumor-targeting peptide (AuNRs@MTSF) and efficiently loaded indocyanine green (ICG). Both in vitro and in vivo analyses demonstrated that AuNRs@MTSF could more effectively reach tumor tissue and enter MCF-7 cells. Furthermore, after loading ICG, AuNRs@MTSF exhibited superior antitumor efficacy compared to other groups by combining photodynamic therapy (PDT) with photothermal therapy (PTT) under near-infrared (NIR) irradiation without inducing any side effects. This work suggests that SF coating of gold nanorods is a potential approach for improving their biocompatibility, and that function-modified AuNRs@SF are effective nanoplatforms for targeted and multimodal tumor therapy.

Chemoenzymatic polymerization (CEP) using enzymes as catalysts is gaining attention as an environmentally friendly method for synthesizing polypeptides. This method proceeds under mild conditions in aqueous solvents and leverages the substrate specificity of enzymes, allowing polymerization reactions to occur without the need to protect reactive side-chain functional groups. However, the monomers used must have esterified C-termini, such as amino acids or oligopeptides. In this study, we used l-lysine (Lys-OH) as a model example and performed one-pot CEP with papain without isolating the esterified lysine. Esterification of Lys-OH was achieved by using hydrochloric acid as a catalyst in ethanol, and one-pot polymerization resulted in poly-l-lysine (polyLys) with a peak top degree of polymerization (DP) of 6 and a maximum DP of 18, with a 31% conversion from the nonesterified lysine. The obtained polyLys was all α-linked, demonstrating that regioselective polymerization was successfully achieved even with one-pot CEP.

Smart materials for tissue engineering have been in extensive use for few decades now. This work delves into the exploration of ultrasound-stimulated piezoelectric and antibacterial silk-based composite films as a pioneering strategy to guide the differentiation of human mesenchymal stem cells into osteogenic lineage without the application of any exogenous growth factors. The study evaluates the biocompatibility and antibacterial attributes of these films, which incorporates Barium Titanate nanoparticles (BTNPs) along with Zinc Oxide nanoparticles for obtaining high piezo modulated stimuli response and antibacterial properties. Further, to enhance the piezoelectric capability, a novel calcium doped Barium Titanate (BCTs) nanoparticles were synthesized and incorporated in silk based films with ZnO. The choice of using calcium as a doping material allows to increase its piezoelectric potential and retain its biocompatibility. The results reveal that, under the influence of ultrasound stimulation, these composite films respond to mechanical cues like low frequency ultrasound stimulations to facilitate lineage-specific differentiation of the seeded human mesenchymal stem cells. Ultrasound stimulations being wireless avoid complicated wired electric circuits and are also known to activate calcium channels in the cells which aids osteogenesis. Significantly, our findings exhibit the profound potential of these films to exploit the piezoelectric properties of BCTs, effectively enhancing the differentiation trajectories of stem cells. Furthermore, their demonstrated antibacterial capacities underscore their pivotal role in infection prevention, an important facet in the domains of tissue engineering and medical implantation. This study strongly suggests the utility of ultrasound-stimulated silk-based composite films in advancing the frontiers of regenerative medicine and tissue engineering.

Implantable medical electronic devices (IMEDs) have attracted great attention and shown versatility for solving clinical problems ranging from real-time monitoring of physiological/ pathological states to electrical stimulation therapy and from monitoring brain cell activity to deep brain stimulation. The ongoing challenge is to select appropriate materials in target device configuration for biomedical applications. Currently, silk-based biomaterials have been developed for the design of diagnostic and therapeutic electronic devices due to their excellent properties and abundant active sites in the structure. Herein, the aim is to summarize the structural characteristics, physicochemical properties, and bioactivities of natural silk biomaterials as well as their derived materials, with a particular focus on the silk-based implantable biomedical electronic devices, such as implantable devices for invasive brain-computer interfaces, neural recording, and in vivo electrostimulation. In addition, future opportunities and challenges are also envisioned, hoping to spark the interests of researchers in interdisciplinary fields such as biomaterials, clinical medicine, and electronics.

Tissue engineering is a dynamic field focusing on the creation of advanced scaffolds for tissue and organ regeneration. These scaffolds are customized to their specific applications and are often designed to be complex, large structures to mimic tissues and organs. This study addresses the critical challenge of effectively characterizing these thick, optically opaque scaffolds that traditional imaging methods fail to fully image due to their optical limitations. We introduce a novel multi-modal imaging approach combining ultrasound, photoacoustic, and acoustic radiation force impulse imaging. This combination leverages its acoustic-based detection to overcome the limitations posed by optical imaging techniques. Ultrasound imaging is employed to monitor the scaffold structure, photoacoustic imaging is employed to monitor cell proliferation, and acoustic radiation force impulse imaging is employed to evaluate the homogeneity of scaffold stiffness. We applied this integrated imaging system to analyze melanoma cell growth within silk fibroin protein scaffolds with varying pore sizes and therefore stiffness over different cell incubation periods. Among various materials, silk fibroin was chosen for its unique combination of features including biocompatibility, tunable mechanical properties, and structural porosity which supports extensive cell proliferation. The results provide a detailed mesoscale view of the scaffolds' internal structure, including cell penetration depth and biomechanical properties. Our findings demonstrate that the developed multimodal imaging technique offers comprehensive insights into the physical and biological dynamics of tissue-engineered scaffolds. As the field of tissue engineering continues to advance, the importance of non-ionizing and non-invasive imaging systems becomes increasingly evident, and by facilitating a deeper understanding and better characterization of scaffold architectures, such imaging systems are pivotal in driving the success of future tissue-engineering solutions.

Biodegradation of natural silk scaffolds made from gauze and satin fabrics was studied both in vitro and in vivo. Experiments were conducted using phosphate-buffered saline (PBS) and Fenton's reagent to model degradation. Samples demonstrated high stability in the model of physiological conditions and varying degradation rates in oxidative stress. In vivo studies in rats showed good biocompatibility of the scaffolds and a gradual reduction in inflammatory responses. The findings highlight the potential of silk scaffolds for use in various areas of regenerative medicine.

Massive hemorrhage and chronic wounds caused by bacterial infections after trauma are significant challenges in clinical practice. An ideal hemostatic wound dressing should simultaneously manage bleeding and prevent bacterial infections and also hold excellent biocompatibility and bioactivities to successfully modulate immune microenvironments to promote wound healing. In this study, a silk fibroin-based light-responsive film was demonstrated to possess effective capacity of light-induced non-compressible hemostasis on liver hemorrhage and tail bleeding in vivo by binding with blood platelets to promote the clotting cascade. The blood loss of the rats was significantly less after C-MASiF films were applied, which were 1223.33 ± 347.9 mg (liver trauma) and 363.33 ± 60.28 mg (tail trimming). Importantly, the films exhibited photo-controllable modulation activity on macrophages through repeated near-infrared irradiation to regulate the immune microenvironment to enhance photodynamic antibacterial therapy. Moreover, the light-responsive silk fibroin film effectively promoted Staphylococcus aureus infected burn wound healing in vivo. The quantity of residual bacteria in the wound sites of mice in the C-MASiF films group (0.05 ± 0.0047 × 108 CFU mL-1) was considerably less than that in the control group (3.18 ± 0.75 × 108 CFU mL-1), and the wound area in the C-MASiF group (78.03% ± 4.12%) was considerably smaller than that in the control group (60.33% ± 8.81%) after 14 days. Overall, this light-responsive silk fibroin film can provide a powerful strategy for wound healing of burns.

3D disordered fibrous network structures (3D-DFNS), such as cytoskeletons, collagen matrices, and spider webs, exhibit remarkable material efficiency, lightweight properties, and mechanical adaptability. Despite their widespread in nature, the integration into engineered materials is limited by the lack of study on their complex architectures. This study addresses the challenge by investigating the structure-property relationships and stability of biomimetic 3D-DFNS using large datasets generated through procedural modeling, coarse-grained molecular dynamics simulations, and machine learning. Based on these datasets, a network deep reinforcement learning (N-DRL) framework is developed to optimize its stability, effectively balancing weight reduction with the maintenance of structural integrity. The results reveal a pronounced correlation between the total fiber length in 3D-DFNS and its mechanical properties, where longer fibers enhance stress distribution and stability. Additionally, fiber orientation is also considered as a potential factor influencing stress growth values. Furthermore, the N-DRL model demonstrates superior performance compared to traditional approaches in optimizing network stability while minimizing mass and computational cost. Structural integrity is significantly improved through the addition of triple junctions and the reduction of higher-order nodes. In summary, this study leverages machine learning to optimize biomimetic 3D-DFNS, providing novel insights into the design of lightweight, high-strength materials.

Silk-fibroin hydrogels have gained considerable attention in recent years for their versatile biomedical applications. The physical properties of a complex hydrogel, comprising silk fibroin and riboflavin, surpass those of the silk fibroin-hydrogel without additives. This study investigates silk fibroin-riboflavin (silk-RIB) hydrogel at the atomistic level to uncover molecular structures and chemical characteristics specific to silk fibroin and riboflavin molecules in an aqueous medium. The interplay between hydrophilic riboflavin and hydrophobic silk fibroin polymers facilitates the formation of solubilized silk fiber, which subsequently evolves into a nano-scale hydrogel over time. Eventually, the interlinked RIB stacks form a scaffold that not only accommodates silk fibroin aggregates but also encloses water pockets, preserving the moisture level and enhancing the thermal conductivity of the hydrogel. To explore water retention properties and the role of ions, two sets of simulations of semi-hydrated hydrogel in the presence and absence of ions are conducted. The presence of ions significantly influences the dynamics of RIB and silk fibroin. Favorable interactions with the ions impede the unrestricted diffusion of these larger molecules, potentially leading to a stable structure capable of retaining water for a prolonged duration. The complete removal of water results in further shrinkage of the anhydrous silk-RIB hydrogel or xerogel (XG), yet its porosity and structural integrity remain intact. These findings offer valuable insights into the behavior of silk fibroin hydrogel and XG, paving the way for materials engineering in aqueous environments to develop biomedical devices with customized functional properties.

Silk fibroin (SF), a natural polymer with very desirable physicochemical and biological properties, is an ideal material for crafting biocompatible scaffolds in tissue engineering. However, conventional methods for removing the sericin layer and dissolving SF often involve environmentally harmful reagents and processes, requiring extensive dialysis procedures to purify the fibers produced. Such processes may also damage the surface and bulk properties of the SF produced. Here, we report a simple, green water degumming method, in which almost complete sericin removal of 30% by weight is achieved in 6 h in boiling water. The SF produced is easily dissolved in formic acid/orthophosphoric acid (90/10, 85/15, and 70/30) mixtures, eliminating the need for salts like LiBr and CaCl2 followed by dialysis and freeze-drying, thus simplifying the process significantly. Additionally, our findings demonstrate significantly enhanced cell viability in electrospun poly(lactic acid)/SF blends. Overall, SF production via water degumming offers an eco-friendly pathway for generating bioactive scaffolds in tissue engineering applications.

Silk fibroin (SF), a pivotal biomaterial, holds immense promise for diverse applications within the realm of bone tissue engineering. SF is an ideal scaffold material with exceptional biocompatibility, mechanical robustness, biodegradability, and bioactivity. A plethora of investigations have corroborated SF's efficacy in supporting bone tissue repair and regeneration. This comprehensive review delves into the structural attributes, physicochemical characteristics, and extraction methodologies of SF. Moreover, it elucidates the strides taken in harnessing SF across a spectrum of forms, including films, hydrogels, scaffolds, electrospun fibers, and composites for bone tissue engineering applications. Moreover, the application bottleneck of SF as a bone repair material is highlighted, and its development prospects and potential biomedical applications are also presented in this review. We expect that this review can inspire the broad interest of a wide range of readers working in the fields of materials science, tissue engineering, biomaterials, bioengineering, and biomedicine.

In recent years, several studies have focused on the development of sustainable, biocompatible, and biodegradable films with potential applications in wound healing and wound dressing systems. Natural macromolecules, particularly proteins, have emerged as attractive alternatives to synthetic polymers due to their biocompatibility, biodegradability, low immunogenicity, and adaptability. Among these proteins, keratin, extracted from waste wool, and fibroin, derived from Bombyx mori cocoons, exhibit exceptional properties such as mechanical strength, cell adhesion capabilities, and suitability for various fabrication methods. These proteins can also be functionalized with antimicrobial, antioxidant, and anti-inflammatory compounds, making them highly versatile for biomedical applications. This review highlights the promising potential of keratin- and fibroin-based films as innovative platforms for wound healing, emphasizing their advantages and the prospects they offer in creating next-generation wound dressing devices.

Hydrogels are widely utilized in industrial and scientific applications owing to their ability to immobilize active molecules, cells, and nanoparticles. This capability has led to their growing use in various biomedical fields, including cell culture and transplantation, drug delivery, and tissue engineering. Among the available synthesis techniques, ionizing-radiation-induced fabrication stands out as an environmentally friendly method for hydrogel preparation. In alignment with the current requirements for cleaner technologies, developing hydrogels using gamma and electron beam irradiation technologies represents a promising and innovative approach for their biomedical applications. A key advantage of these methods is their ability to synthesize homogeneous three-dimensional networks in a single step, without the need for chemical initiators or catalysts. Additionally, the fabrication process is controllable by adjusting the radiation dose and dose rate.

The pursuit of materials, particularly plastics, with a minimal ecological footprint throughout their circular lifecycle, is crucial for advancing sustainable materials development. Living materials composed of embedded yet active organisms can leverage endogenous biotic resources to achieve functional materials that align with sustainability goals. However, current living material systems face challenges such as weak mechanical properties, limited environmental adaptability, and restricted cellular functionality. In this study, we propose an approach to sustainable living materials by incorporating active organisms into silk-based plastics through a plasticizer-assisted thermal molding process. We investigate the mechanism of structure formation in these materials, correlating manufacturing performance to the resulting secondary structure. These silk-based plastics provide a protective matrix for probiotics, ensuring their survival through the harsh gastrointestinal tract and enhancing intestinal delivery. Similarly, soil rhizobacteria encapsulated within the plastics exhibit long-term protease activity, accelerating plastic degradation upon soil exposure. This work demonstrates the potential of sustainable plastics as a form of living materials, where active organisms are processed, entrapped, retain metabolic functions, and are protected in harsh environments.

Human intestinal organoids (HIOs) are vital for modeling intestinal development, disease, and therapeutic tissue regeneration. However, their susceptibility to stress, immunological attack, and environmental fluctuations limits their utility in research and therapeutic applications. This study evaluated the effectiveness of temporary silk protein-based layer-by-layer (LbL) nanoencapsulation technique to enhance the viability and functions of HIOs against common biomedical stressors, without compromising their native functions. Cell viability and differentiation capacity are assessed, finding that nanoencapsulation significantly improved HIO survival under the various environmental perturbations studied without compromising cellular functionality. Post-stress exposures, the encapsulated HIOs still successfully differentiated into essential intestinal cell types such as enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Moreover, the silk nanocoatings effectively protected against environmental stressors such as ultraviolet (UV) light exposure, protease degradation, antibody binding, and cytokine-induced inflammation. This nanoencapsulation technique shows promise for advancing HIO applications in disease modeling, drug testing, and potential transplantation therapies.

The influence of plasticizer glycerol (GLY) on the mechanical, structural, and thermal properties of silk fibroin (SF)/sodium alginate (SA) biocomposite films was investigated in detail. As the SF/SA ratio increased up to 65%, the SF content significantly improved the Tensile strength (σT), Young's modulus (Ey) but reduced the elongation at break (εb). To modify and enhance the elasticity and flexibility of the biocomposite films, the GLY as a plasticizer was used at different ratio from 20 to 50% for each SF/SA biocomposite films. Although the extensibility of the films was improved greatly with increasing GLY ratio, σT and Ey reduced significantly. The effect was observed more apparently for the GLY ratio starting from 35%. It was also shown that crystallinity index in the Amide I region increased as the SF/SA ratio increased to 65%. Increasing SF content improved the thermal stability of the SF/SA biocomposites. The XRD results showed that crystallinity was increased as SF/SA ratio increased. Stress-relaxation of SF/SA (30%) biocomposite films plasticized with GLY revealed that each kind of plasticized films showed a viscoelastic behavior and a fast relaxation in the first stage (1-2 min) of the processes and then continued slowly. The GLY increased the extensibility and elasticity limit of the SF/SA (30%) composite films. During the strain recovery processes, the plasticized composite films recovered completely in a quite shorter time than that of unplasticized films. It was observed higher the GLY content, the recovery times became shorter.

3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health-related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D-printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state-of-the-art in 3D-printed functional polymeric health-related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D-printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self-powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.

Silk fibroin (SF), the core structural protein derived from Bombyx mori silk, is extensively employed in tissue engineering and regenerative medicine due to its exceptional mechanical properties, favorable biocompatibility, tunable biodegradability, and versatile processing capabilities. Despite these advantages, current research predominantly focuses on SF biomaterials as structural scaffolds or drug carriers, often overlooking their potential role in modulating cellular behavior and tissue regeneration. This review aims to present a comprehensive overview of the inherent biological effects of SF biomaterials, independent of any exogenous biomolecules, and their implications for various tissue regeneration. It will cover in vitro cellular interactions of SF with various cell types, including stem cells and functional tissue cells such as osteoblasts, chondrocytes, keratinocytes, endothelial cells, fibroblasts, and epithelial cells. Moreover, it will summarize in vivo immune responses, cellular responses, and tissue regeneration following SF implantation, specifically focusing on vascular, bone, skin, cartilage, ocular, and tendon/ligament regeneration. Furthermore, it will address current limitations and future perspectives in the design of bioactive SF biomaterials. A comprehensive understanding of these cellular interactions and the biological effects of SF is crucial for predicting regenerative outcomes with precision and for designing SF-based biomaterials tailored to specific properties, enabling broader applications in regenerative medicine.

Mucins are key components of innate immune defense and possess remarkable abilities to manage pathogenic microbes while supporting beneficial ones and maintaining microbial homeostasis at mucosal surfaces. Their unique properties have garnered significant interest in developing mucin-inspired materials as novel therapeutic strategies for selectively controlling pathogens without disrupting the overall microbial ecology. However, natural mucin production is challenging to scale, driving the need for simpler materials that reproduce mucin's bioactivity. In this work, we generated silk-based glycopolymers with different monosaccharides (GalNAc, GlcNAc, NeuNAc, GlcN, and GalN) and different grafting densities. Using the oral cavity as a model system, we treated in vitro cultures of pathogenic Streptococcus mutans and commensal Streptococcus sanguinis with our glycopolymers, finding that silk-tethered GalNAc uniquely prevented biofilm formation without affecting overall bacterial growth of either species. This relatively simple material reproduced mucin's virulence-neutralizing effects while maintaining biocompatibility. These mucin-inspired materials represent a valuable tool for preventing infection-related harm and offer a strategy for the domestication of pathogens in other environments.

Silk fibroin is a naturally abundant biomaterial renowned for its excellent biocompatibility and biodegradability, making it a promising candidate for biomedical applications like wound dressings. However, traditional silk fibroin materials often lack sufficient mechanical strength, adhesion, and the ability to modulate inflammation and oxidative stress-factors crucial for effective wound healing. To address these limitations, regenerated silk fibroin/magnesium ion [RSF/Mg(II)] composite films were developed by incorporating Mg(II) ions into RSF solutions. These films were characterized using Raman spectroscopy, mechanical testing, and biocompatibility assessments, and their wound-healing efficacy was evaluated in a mouse skin defect model. The RSF/Mg(II) composite films exhibited superior adhesion, higher transparency, and enhanced mechanical flexibility compared to pristine RSF films. They also demonstrated anti-inflammatory and antioxidative properties, effectively reducing cell apoptosis and reactive oxygen species levels in vitro. In vivo, the RSF/Mg Mg(II) composite films significantly accelerated wound healing in mice, improving epidermal thickness, collagen deposition, and promoting blood vessel formation. This study highlights the potential of RSF/Mg(II) composite films as advanced wound dressings with improved biocompatibility and biological activity, offering valuable insights for the development of Mg(II) ion-based biomaterials in wound healing and tissue regeneration applications.

Silk fibroin (SF) is a natural protein generated from the Bombyx mori silkworm cocoons. It is useful for many different material applications. Versatile aqueous process engineering options can be used to support the morphological and structural modifications of silk materials related to tailored physical, chemical, and biological properties. Conventional solution-based processing methods, while effective, present process control limitations, thus, thermoplastic molding of regenerated SF-based composites was pursued to fabricate dense, functionalized plastics consisting of silk and curcumin. Curcumin, the active compound in turmeric (Curcuma longa) was incorporated into SF during the high-temperature processing, with the objective to investigate composite thermoplastics with enhanced biological properties from the curcumin due to the protective role of silk during processing. The results showed that a significantly higher amount of curcumin (∼25-fold) could be added into thermoplastic molded silk materials compared with the solution route, attributed to the hydrophobicity and low solubility of curcumin in solution-based routes. The curcumin-incorporated silk thermoplastics provided stability in acidic environments like the human gut, and slow curcumin (∼2% over 8 days) release from the materials. The protective silk-curcumin materials supported improved cytocompatibility with immortalized human colorectal adenocarcinoma (Caco-2) cells at high doses. The intestinal epithelial barrier integrity based on zonula occluden 1 (ZO-1) testing showed that the higher amount of curcumin in the thermoplastic molded silk had no negative effects on the intestinal barrier. The functionalized silk-based plastics also displayed microwave stability and antibacterial efficacy against both Gram-positive S. aureus and Gram-negative E. coli. These silk-based sustainable plastics, functionalized with curcumin, offer potential utility for a range of consumer and medical devices.

Electrospinning is a remarkably straightforward and adaptable technique that can be employed to process an array of synthetic and natural materials, resulting in the production of nanoscale fibers. It has emerged as a novel technique for biomedical applications and has gained increasing popularity in the research community in recent times. In the context of tissue repair and tissue engineering, there is a growing tendency toward the integration of biomimetic scaffolds and bioactive macromolecules, particularly proteins and growth factors. The design of 'smart' systems provides not merely physical support, but also microenvironmental cues that can guide regenerative tissue repair. Electrospun nanofibrous matrices are regarded as a highly promising tool in this area, as they can serve as both an extracellular matrix (ECM)-mimicking scaffold and a vehicle for the delivery of bioactive proteins. Their highly porous architecture and high surface-to-volume ratio facilitate the loading of drugs and mass transfer. By employing a judicious selection of materials and processing techniques, there is considerable flexibility in efficiently customizing nanofiber architecture and incorporating bioactive proteins. This article presents a review of the strategies employed for the structural modification and protein delivery of electrospun nanofibrous materials, with a focus on the objective of achieving a tailored tissue response. The article goes on to discuss the challenges currently facing the field and to suggest future research directions.

Critical-sized bone defects present a major challenge in healthcare, necessitating innovative solutions like bone tissue engineering (BTE) to address these issues. Surface engineering of bone scaffolds plays a crucial role in BTE by integrating natural polymers with advanced techniques to closely replicate the bone microenvironment, enhancing cellular responses such as adhesion, proliferation, and osteogenic differentiation. Natural polymers like collagen, chitosan, gelatin, hyaluronic acid, and alginate are used in various surface modification methods, including physical adsorption, covalent immobilization, electrospinning, and layer-by-layer assembly. This review provides a thorough analysis of these surface modification strategies across metallic, ceramic, and polymeric scaffolds, along with characterization methodologies, preclinical studies, and future prospects. By analysing recent research, the review offers valuable insights for advancing natural polymer-based surface engineering and developing next-generation scaffolds with improved bone regenerative capabilities.

The choice of suitable materials and effective structural design are crucial in influencing the therapeutic outcomes of bone tissue engineering scaffolds. This study introduces a controllable biodegradable composite scaffold composed of flat silkworm cocoon (FSC) and polylactic acid (PLA) as an innovative strategy for promoting bone healing in complex injuries. We focused on optimizing the scaffold's structural design, mechanical properties, and underlying mechanisms of osteogenesis. Initial experiments established the parameters for hot pressing the FSC, followed by mechanical performance tests to identify the optimal preparation conditions. Composite scaffolds incorporating PLA films were subsequently fabricated using these optimized parameters. The results indicate that the FSC/PLA composite scaffold exhibits outstanding biocompatibility, mechanical strength, and in vitro mineralization capabilities, alongside an appropriate degradation rate. Furthermore, the composite scaffolds demonstrated significant potential in promoting osteogenic differentiation and facilitating macrophage polarization toward an anti-inflammatory M2 phenotype. In vivo implantation of the scaffold in defective regions enhanced osteogenesis and mitigated inflammatory responses associated with degradation. This investigation presents an optimal composite scaffold that closely mimics the complex structure of bone, offering a novel approach to enhance bone regeneration and effectively address substantial bone defects.

Ocular drugs have low absorption because of the unique environment in the eye, making ocular drugs one of the most challenging pharmaceutical initiatives. Liposomes have shown to be a promising ocular drug delivery system over the years because of enhanced drug absorption, biocompatibility, and biodegradability. Utilising a mucoadhesive material alongside liposomes could be a promising strategy to increase the therapeutic efficacy of ocular drugs. The present study aimed to develop a silk fibroin (SF)-coated liposomal formulation as an ocular drug delivery system. Regenerated silk fibroin (a novel biopolymer) was coated on ciprofloxacin hydrochloride-loaded liposomes (CPH-SFLs). Studies were carried out on the morphology, drug encapsulation efficiency, and in vitro drug release. Human corneal epithelial cells (HCEC) were used to examine the cellular adherence and cytotoxicity of CPH-SFLs. CPH-SFLs had an average particle size of 183 ± 3 nm as opposed to 169 ± 4 of blank SFLs. CPH-loaded SFLs lacked the endothermic peak of CPH at 150 °C, indicating that the CPH molecules were trapped in the SF polymeric grid. In the case of the formulations, 25 %-45 % of the medicine was released at a relatively fast pace over the course of the first 4 h and then at a slower rate over the course of the next 12-24 h. CPH-SFLs demonstrated sustained drug release and high in vitro ocular penetration of CPH. The MTT test was conducted to gauge the viability of HCECs, cell viability was higher than 85 %, demonstrating that CPH-SFLs had no adverse effects on HCEC. The observed CPH-SFL adhesions to HCECs were swift and persistent, like the cellular uptake of CPH-SFLs by HCECs. When compared to CPH-solution, the produced formulation CPH-SFLs demonstrated significantly (P < 0.0001) greater susceptibility. The studies concluded that SF-coated liposomes could be the most viable ocular drug delivery in comparison to conventional eye drops.

Bombyx mori silk fibroin is a promising biopolymer with notable mechanical strength, biocompatibility, and potential for diverse biomedical applications, such as tissue engineering scaffolds, and drug delivery. These properties are intrinsically linked to the structural characteristics of silk fibroin, making it essential to understand its molecular stability under varying environmental conditions. This study employed molecular dynamics simulations to examine the structural stability of silk I and silk II conformations of silk fibroin under changes in temperature (298 K to 378 K) and pressure (0.1 MPa to 700 MPa). Key parameters, including Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Radius of Gyration (Rg) were analyzed, along with non-bonded interactions such as van der Waals and electrostatic potential energy. Our findings demonstrate that both temperature and pressure exert a destabilizing effect on silk fibroin, with silk I exhibiting a higher susceptibility to destabilization compared to silk II. Additionally, pressure elevated the van der Waals energy in silk I, while temperature led to a reduction. In contrast, electrostatic potential energy remained unaffected by these environmental conditions, highlighting stable long-range interactions throughout the study. Silk II's tightly packed β-sheet structure offers greater resilience to environmental changes, while the more flexible α-helices in silk I make it more susceptible to structural perturbations. These findings provide valuable insights into the atomic-level behavior of silk fibroin, contributing to a deeper understanding of its potential for applications in environments where mechanical or thermal stress is a factor. The study underscores the importance of computational approaches in exploring protein stability and supports the continued development of silk fibroin for biomedical and engineering applications.

With the rapid development of the global economy and the continuous consumption of fossil resources, sustainable and biodegradable natural biomass has garnered extensive attention as a promising substitute for synthetic polymers. Due to their hierarchical and nanoscale structures, natural biopolymers exhibit remarkable mechanical properties, along with excellent innate biocompatibility and biodegradability, demonstrating significant potential in various application scenarios. Among these biopolymers, proteins and polysaccharides are the most commonly studied due to their low cost, abundance, and ease of use. However, the direct processing/conversion of proteins and polysaccharides into their final products has been a long-standing challenge due to their natural morphology and compositions. In this review, we emphasize the importance of processing natural biopolymers into high-value-added products through sustainable and cost-effective methods. We begin with the extraction of four types of natural biopolymers: cellulose, chitosan, eggshell membrane, and silk fibroin. The processing and post-functionalization strategies for these natural biopolymers are then highlighted. Alongside their unique structures, the versatile potential applications of these processable natural biopolymers in biomedical engineering, biosensors, environmental engineering, and energy applications are illustrated. Finally, we provide a summary and future outlook on processable natural biopolymers, underscoring the significance of converting natural biopolymers into valuable biomaterial platforms.

Alveolar ridge loss presents difficulties for implant placement and stability. To address this, alveolar ridge preservation (ARP) is required to maintain bone and avoid the need for ridge augmentation using socket grafting. In this study, a scaffold for ARP was created by fabricating a 3D porous dense microfiber silk fibroin (mSF) embedded in poly(vinyl alcohol) (PVA), which mimics the osteoid template. The research utilized a freeze-thawing technique to create a mimicked osteoid 3D porous scaffold by incorporating different amounts of mSF into the PVA, namely, 1%, 3%, 5% and 7%. Subsequently, a 3D profilometer machine and a scanning electron microscope were employed to examine the morphology and size of the mSF and the mimicked osteoid 3D porous scaffold in all groups. Thermal characteristics and crystalline structure were analyzed before assessing the water contact angle, swelling behavior, degradation and mechanical properties. The experiment evaluated the biological performance of the mimicked osteoid 3D porous scaffold by examining the efficacy of osteoblast cell adhesion, proliferation, viability, protein synthesis, alkaline phosphatase (ALP) activity and calcium synthesis. Finally, the ability of osteoblast cells to regulate the osteoid matrix deposition on the osteoid 3D porous scaffold was assessed by mimicking the dynamic bone environment using rat mesenchymal stem cells. The findings suggest that incorporating mSF into PVA enhances the interconnective pore size, crystalline structure and thermal behavior of the mimicked osteoid 3D porous scaffold. The hydrophilicity of PVA decreased with an increase in the proportion of mSF, while a higher proportion of mSF resulted in increased swelling and mechanical characteristics. Incorporating a greater proportion of mSF, specifically 5% and 7%, led to a reduced rate of degradation. The addition of 5% mSF to the PVA 3D porous scaffold resulted in remarkable biological properties and excellent osteoconductive activity.

Nano/micro hybrid scaffolds in long-term healing tissue engineering can simultaneously offer both mechanical and biological properties. In this study, a hybrid scaffold was fabricated through electrospinning of polycaprolactone (PCL)-chitosan (Cs)/ multi-walled carbon nanotubes (MWCNTs) based nanofibers onto a chemically functionalized knitted silk substrate (F-Silk) and the scaffold were evaluated with regard to morphology, chemical and crystalline structure, hydrophilicity, mechanical properties, bioactivity, biodegradability, and cellular behavior. Chemical functionalization of silk using N-hydroxysuccinimide (NHS) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) resulted in greater integrity in the formation of nanofibers onto the microfibers. The presence of MWCNTs significantly reduced the contact angle of the scaffolds from 79.72° ± 2.72 to 68.92° ± 5.63. Chemical functionalization of silk, the presence of nanofiber coating, and the presence of MWCNTs increased the ultimate tensile strength of the hybrid scaffolds by 18 %, 20 %, and 30 % compared to raw silk fabric, respectively. The presence of MWCNTs and chemical functionalization of knitted silk increased the bioactivity and reduced the degradation rate of hybrid scaffolds. The increase in the amount of carboxyl groups as a result of adding 0.5 wt% of MWCNTs significantly improved the adhesion, growth and proliferation of chondrocyte cells on the hybrid scaffolds as observed through cell morphology. According to the obtained results, hybrid scaffold based on PCL-Cs-MWCNTs/F-silk can be a suitable option for further research in cartilage tissue engineering.

The utilization of silk cocoons in the production of lightweight and tough composites has been gaining increasing attention. However, the limited applications of normal silk cocoons (NSC) are attributed to their small size and irregular shape. To overcome this deficiency, flat silk cocoons (FSC) with a similar structure and controllable size were prepared. Next, we systematically characterized and compared the microstructures, morphologies, compositions, thermal properties, and mechanical properties of FSC with NSC. Subsequently, FSC was successfully utilized to fabricate a novel silk fibroin fiber reinforced sericin matrix composite (HPFSC) using a hot pressing method, followed by the analysis of its microstructure evolution, mechanical properties, failure modes, and theoretical modeling. This composite has outstanding mechanical properties including hardness, modulus, and strength. HPFSC has a relatively low density of ~1.3 g/cm3, whose absorbed impact energy can reach a maximum value of 11.1 J/mm, exceeding that of most engineering materials, such as aluminum alloy, ceramics, glass, and carbon fiber composites. The exceptional performance of HPFSC can be attributed to the reduced porosity, enhanced bonding between silk fibroin fibers facilitated by sericin, and their structural transformation. This study offers valuable guidance for the fabrication of lightweight and impact-resistant composites using flat silk cocoons.

Silk fibroin is a fiber-forming protein derived from the thread of Bombyx mori silkworm cocoons. This biocompatible protein, under the kosmotropic influence of potassium phosphate, can undergo supramolecular self-assembly driven by a random coil to β-sheet secondary structure transition. By leveraging concurrent nonspecific adsorption and self-assembly of silk fibroin, we demonstrate an interfacial phenomenon that yields adherent, defect-free nanothin protein coatings that grow continuously in time, without observable saturation in mass deposition. This noncovalent growth of silk fibroin coatings is a departure from traditionally studied protein adsorption phenomena, which generally yield adsorbed layers that saturate in mass with time and often do not completely cover the surface. Here, we explore the fundamental mechanisms of coating growth by examining the effects of coating solution parameters that promote or inhibit silk fibroin self-assembly. Results show a strong dependence of coating kinetics and structure on solution pH, salt species, and salt concentration. Moreover, coating growth was observed to occur in two stages: an early stage driven by protein-surface interactions and a late stage driven by protein-protein interactions. To describe this phenomenon, we developed a kinetic adsorption model with Langmuir-like behavior at early times and a constant steady-state growth rate at later times. Structural analysis by FTIR and photoinduced force microscopy show that small β-sheet-rich structures serve as anchoring sites for absorbing protein nanoaggregates, which is critical for coating formation. Additionally, β-sheets are preferentially located at the interface between protein nanoaggregates in the coating, suggesting their role in forming stable, robust coatings.

This is a Perspective on nature as a story-teller, where inputs of evolution drove the remarkable protein designs found in silks. This selection process has resulted in silk materials with novel chemistry and properties to support organism survival in nature, yet with newfound utility in everything from comic books and automobiles to medicine. With growing global concerns related to environmental health, silks also serve as an invaluable instructional guide to the future of sustainable material designs.

Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK.

The tumor microenvironment (TME) assumes a pivotal role in the treatment of oncological diseases, given its intricate interplay of diverse cellular components and extracellular matrices. This dynamic ecosystem poses a serious challenge to traditional research methods in many ways, such as high research costs, inefficient translation, poor reproducibility, and low modeling success rates. These challenges require the search for more suitable research methods to accurately model the TME, and the emergence of 3D bioprinting technology is transformative and an important complement to these traditional methods to precisely control the distribution of cells, biomolecules, and matrix scaffolds within the TME. Leveraging digital design, the technology enables personalized studies with high precision, providing essential experimental flexibility. Serving as a critical bridge between in vitro and in vivo studies, 3D bioprinting facilitates the realistic 3D culturing of cancer cells. This comprehensive article delves into cutting-edge developments in 3D bioprinting, encompassing diverse methodologies, biomaterial choices, and various 3D tumor models. Exploration of current challenges, including limited biomaterial options, printing accuracy constraints, low reproducibility, and ethical considerations, contributes to a nuanced understanding. Despite these challenges, the technology holds immense potential for simulating tumor tissues, propelling personalized medicine, and constructing high-resolution organ models, marking a transformative trajectory in oncological research.

Natural biopolymers have a rich history, with many uses across the fields of healthcare and medicine, including formulations for wound dressings, surgical implants, tissue culture substrates, and drug delivery vehicles. Yet, synthetic-based materials have been more successful in translation due to precise control and regulation achievable during manufacturing. However, there is a renewed interest in natural biopolymers, which offer a diverse landscape of architecture, sustainable sourcing, functional groups, and properties that synthetic counterparts cannot fully replicate as processing and sourcing of these materials has improved. Proteins and polysaccharides derived from various sources (crustaceans, plants, insects, etc.) are highlighted in this review. We discuss the common types of polysaccharide and protein biopolymers used in healthcare and medicine, highlighting methods and strategies to alter structures and intra- and interchain interactions to engineer specific functions, products, or materials. We focus on biopolymers obtained from natural, nonmammalian sources, including silk fibroins, alginates, chitosans, chitins, mucins, keratins, and resilins, while discussing strategies to improve upon their innate properties and sourcing standardization to expand their clinical uses and relevance. Emphasis will be placed on methods that preserve the structural integrity and native biological functions of the biopolymers and their makers. We will conclude by discussing the untapped potential of new technologies to manipulate native biopolymers while controlling their secondary and tertiary structures, offering a perspective on advancing biopolymer utility in novel applications within biomedical engineering, advanced manufacturing, and tissue engineering.

Vascular covered stents play a significant therapeutic role in cardiovascular diseases. However, the poor compliance and biological inertness of commercial materials cause post-implantation complications. Silk fibroin (SF), as a biomaterial, possesses satisfactory hemocompatibility and tissue compatibility. In this study, we developed a silk film for use in covered stents by employing a layer-by-layer self-assembly strategy with regenerated SF on silk braiding fabric. We investigated the effects on the mechanical properties of the silk films in detail, which were closely correlated with fabric parameters and layer-by-layer self-assembly. The results showed that there was a significant relationship between these factors and both the compliance and mechanical strength. The 1 × 2/90°/100/SF6 film exhibited excellent mechanical properties. Notably, compliance reached 2.6%/100 mmHg, matching that of the human saphenous vein. Thus, this strategy shows promise in developing a novel covered stent, with biocompatible and comprehensive mechanical properties, and significant potential for clinical applications.

Platelet-rich fibrin (PRF) is a protein matrix with growth factors and immune cells extracted from venous blood via centrifugation. Previous studies proved it a beneficial biomaterial for bone and soft tissue regeneration in dental surgeries. Researchers have combined PRF with a wide range of biomaterials for composite preparation as it is biocompatible and easily acquirable. The results of the studies are difficult to compare due to varied research methods and the fact that researchers focus more on the PRF preparation protocol and less on the interaction of PRF with the chosen material. Here, the literature from 2013 to 2024 is reviewed to help surgeons and researchers navigate the field of commonly used biomaterials in maxillofacial surgeries (calcium phosphate bone grafts, polymers, metal nanoparticles, and novel composites) and their combinations with PRF. The aim is to help the readers select a composite that suits their planned research or medical case. Overall, PRF combined with bone graft materials shows potential for enhancing bone regeneration both in vivo and in vitro. Still, results vary across studies, necessitating standardized protocols and extensive clinical trials. Overviewed methods showed that the biological and mechanical properties of the PRF and material composites can be altered depending on the PRF preparation and incorporation process.

Silk is a widely accepted biomaterial for tissue regeneration owing to its tunable biomechanical properties and ease of chemical modification. However, a number of aspects associated with its clinical use are still debated. Indeed, to achieve clinical success, a biomaterial must favorably interact with host tissues without evoking local or systemic immuno-inflammatory responses. The analysis of immune responses associated with silk under in vitro and in vivo conditions provides useful insights, improving the understanding of the functional characteristics of silk biomaterials and further promoting their clinical application. Silk evokes moderate immune responses upon implantation in vivo, depending on the material structure, fabrication method, degradation time, and implantation in soft or hard tissue sites, which rapidly subside within a few days/weeks. In vitro studies indicate that its immune-stimulatory properties are largely due to inherent protein conformation and differential processing parameters. Strategically controlled levels of immune responses in vivo with marginal immunogenicity of silk-based biomaterials may contribute to matrix remodeling and replacement by native tissue matrix around the implanted site. Therefore, immunomodulatory strategies should be developed to promote the use of silk-based biomaterials as promising candidates for numerous clinical applications.

Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement.

The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration.

The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed.

This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine-inspired approaches, immunotherapy, gene therapy, cell-based therapy, tissue engineering, nanotechnology, and phototherapy.

These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor-beta (TGF-β), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), all of which contribute to the repair of injured tendons.