Search Results (18)

Programmable hydrogel actuators represent an innovative group of adaptive soft matter systems, which are able to respond to external stimuli with controllable mechanical movements for biomedical and bioengineering purposes. Natural silk fibroin (SF) is known to be a peculiar biomaterial, since it can exhibit controllable β-sheet-induced structural transitions, hierarchical self-assemblies, high biocompatibility, and mechanical adaptability, thus representing an ideal candidate for the development of dynamic hydrogels. In contrast to earlier reviews which focused more on SF hydrogel synthesis or biomedical applications, this review presents a mechanism-based understanding of programmable bioactuation by carefully correlating molecular design, network formation, stimuli responsiveness, and macroscopic deformation. Recent developments in SF hydrogel actuators are critically compared in terms of actuation principles, deformation behaviors, response dynamics, mechanical robustness, and functionalization, noting the natural compromise between fast response, strength generation, and durability in such materials. Novel concepts like nanocomposite materials, bioinspired designs, shape memory systems, and 4D printing are described as efficient ways to improve programmable deformation and functionality in soft materials. In addition, the biomedical opportunities of responsive SF hydrogels in wound healing, drug delivery, tissue engineering, wearable biosensors, and soft robots are critically discussed in relation to existing barriers for translation into practice. Combining mechanistic understanding with the comparative assessment of the performance of hydrogels is a basis for developing a complete rationale for the design of the next generation of SF hydrogel actuators and smart shape deformations. Full article

The emergence of multifunctional wound dressings represents a significant transformation in the care of cutaneous tissue injuries, providing advanced solutions that surpass traditional dressings. This study is poised to fabricate multifunctional hydrogels through dual-dynamic cross-linking, integrating antibacterial and antioxidant properties, which are capable of accelerating wound healing while improving therapeutic outcomes. The hydrogel, which exhibits excellent adhesion, rapid self-healing ability, and on-demand removability, was synthesized employing poly(vinyl alcohol) (PVA)–borax as the backbone, followed by the incorporation of silk fibroin (SF), tannic acid (TA), and chitosan (CS). Total saponins of Panax notoginseng flower buds (PNF) with anti-inflammatory and angiogenic properties were loaded in porous structural materials yielding the PBCTS@PNF hydrogel. The prepared hydrogel exhibited outstanding antioxidant properties and cytocompatibility, along with favorable antibacterial capabilities, achieving inhibition rates of 84.30 ± 2.34% against Escherichia coli (E. coli) and 98.12 ± 0.76% against Staphylococcus aureus (S. aureus), respectively. Animal experiments demonstrated that PBCTS@PNF significantly reduced inflammation and promoted multidimensional tissue regeneration, encompassing re-epithelialization, neovascularization, and hair follicle regeneration, along with ordered collagen matrix organization, leading to substantially accelerated wound healing. The multifunctional PBCTS@PNF hydrogel provides a potent bioengineered therapeutic platform for wound healing management through the synergistic interplay among antibacterial, anti-inflammatory, and tissue regenerative functionalities. Full article

Background: Cryopreservation is a key enabling technology for cell-based therapies and regenerative medicine; however, the toxicity associated with permeating cryoprotective agents such as dimethyl sulfoxide (DMSO) remains a major limitation, particularly for applications requiring repeated cell administration or long-term storage. Methods: In this study, silk-derived proteins, namely silk fibroin and silk sericin, were investigated as biomaterial-based cryoprotective additives to enable DMSO-sparing cryopreservation strategies. Mouse fibroblasts (3T3) were cryopreserved at −80 °C using conventional DMSO-based media, silk-only formulations, and hybrid formulations combining silk proteins with reduced DMSO concentrations. Post-thaw cell adhesion, metabolic activity, membrane integrity, and cytoskeletal organization were systematically evaluated over a 7-day culture period. Results: Complete replacement of DMSO with silk proteins was insufficient to ensure cell survival, confirming the essential role of permeating cryoprotectants for intracellular protection. In contrast, formulations combining silk fibroin or sericin with 5% (v/v) DMSO supported robust post-thaw viability, preserved cytoskeletal architecture, and promoted favorable recovery kinetics, with cell viability consistently exceeding established biocompatibility thresholds and higher than samples with DMSO alone. Conclusions: These findings support the integration of biomaterial-based components into hybrid cryopreservation formulations and provide design principles relevant to the preservation of more complex multicellular systems. Full article

Background and Objectives: Corneal opacity is the fifth global cause of blindness and moderate-to-severe visual impairment due to scar tissue formation. The purpose of this study is to provide an integrated overview of the current state of corneal engineering strategies focused on the comparison with healthy corneas. It aims to identify engineering strategies that would result in functional corneas, providing real alternatives to donor corneal transplants. Materials and Methods: systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and according to the protocol with the ID: CRD420250654641 at the PROSPERO database. The focus question, prompted by considering the shortage of human corneal grafts, was: what is the performance of bioengineered corneal grafts in experimental animal models when compared with healthy eyes in the restoration of corneal anatomy and function? Results: Incorporating human corneal epithelial cells w/ or w/o human corneal stromal stem cells into a gelatin methacrylate and polyethylene glycol diacrylate matrix emerges as the leading option for epithelial layer regeneration. Human and bovine decellularized corneas, porcine corneal ECM in Gelatin methacrylate, dual layered collagen vitrigel and tissue-engineered human anterior hemi-corneas have shown promise for simultaneous regeneration of the corneal stromal and epithelial layers. Corneal stromal tissue regeneration could be positively impacted by transplantation with grafts derived from aligned self-lifting analogous tissue equivalents and collagen-based hydrogels. Finally, scaffolds of silk fibroin and human purified type I collagen represent promising approaches for corneal endothelial regeneration, though their effectiveness is contingent upon integration with endothelial cells. Conclusions: Collectively, these findings contribute to the growing body of evidence supporting the potential of tissue-engineered corneal substitutes as viable therapeutic options for corneal blindness and vision impairment. Assessing the optical and functional properties of the regenerated cornea should be a cornerstone in all studies aiming to evaluate their clinical effectiveness. Full article

Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein conformation, which can be precisely regulated through processing and fabrication strategies. Recent advances in bioengineering have further expanded the capabilities of BMSF, enabling the development of biomaterials with engineered architectures, tailored microtopographies, and enhanced bioactivity. These technological developments have facilitated the design of scaffolds that more effectively guide tissue regeneration and enhance functional outcomes. Such constructs have demonstrated promising outcomes in the regeneration of bone, cartilage, vascular, neural, corneal, and skin tissues. This review summarises current progress while emphasising emerging trends that couple BMSF’s unique molecular features with immune-responsive design, instructive microarchitectures that guide cell behaviour, composite scaffold design, and functionalisation with bioactive molecules. BMSF has been positioned as a structurally adaptable and biologically instructive platform whose continued progression will depend on integrating advanced fabrication, mechanistic understanding, and translational standardisation. Full article

Silk fibroin has recently gained considerable attention as a promising biomaterial for use in medical and bioengineering technologies due to its biocompatibility and favorable mechanical properties. In this study, composite gel based on silk fibroin microparticles and carboxymethyl cellulose was developed, characterized by a viscous, homogeneous white mass containing uniformly distributed fibroin microparticles ranging from 1 to 20 μm in size. The gel exhibited a kinematic viscosity of 36.5 × 10⁻⁶ St, allowing for convenient application to wounds using a syringe or spatula while preventing uncontrolled spreading. The cytocompatibility of the gel was confirmed using the methylthiazol tetrazolium (MTT) assay, which showed no cytotoxic effects on 3T3 fibroblast cells. Furthermore, the gel remained stable for over one year when stored at 10 °C, in contrast to conventional fibroin solutions, which typically lose stability within a month under similar conditions. In a full-thickness skin wound model in rats, the application of the gel significantly accelerated skin regeneration, with complete wound closure observed by day 15, compared with 30 days in the control group. Histological analysis confirmed the restoration of all skin layers. These findings demonstrate the high potential of the gel for applications in regenerative medicine and tissue engineering. Full article

This study examines the hemocompatibility of gellan-gum-based hybrid hydrogels, with varying gellan-gum concentrations and constant sodium alginate and silk fibroin concentrations, respectively, in accordance with ISO 10993-4 standards. While previous studies have focused on cytocompatibility, the hemocompatibility of these hydrogels remains underexplored. Hydrogels were formulated with 0.3%, 0.5%, 0.75%, and 1% gellan gum combined with 3% silk fibroin and 4.2% sodium alginate separately, using physical and ionic cross-linking. Swelling behavior was analyzed in phosphate (pH 7.4) and acetic (pH 1.2) buffers and surface morphology was examined by scanning electron microscopy (SEM). Hemocompatibility tests included complete blood count (CBC), coagulation assays, hemolysis index, erythrocyte morphology, and platelet adhesion analysis. Results showed that gellan gum–sodium alginate hydrogels exhibited faster swelling than gellan gum–silk fibroin formulations. SEM indicated smoother surfaces with sodium alginate, while silk fibroin increased roughness, further amplified by higher gellan-gum concentrations. Hemocompatibility assays confirmed normal profiles in formulations with 0.3%, 0.5%, and 0.75% gellan gum, while 1% gellan gum caused significant hemolytic and thrombogenic activity. These findings highlight the excellent hemocompatibility of gellan-gum-based hydrogels, especially the sodium alginate variants, supporting their potential in bioengineering, tissue engineering, and blood-contacting biomedical applications. Full article

Silk and polycaprolactone (PCL), derived from natural and synthetic sources, respectively, are suture materials commonly used in surgery. Beyond their application in sutures, they are also compelling subjects in regenerative medicine and tissue engineering. This study evaluated the effects of degummed silk microfibers compared to electrospun PCL microfibers of a similar diameter on chondrocyte behavior. The two types of microfibers were analyzed using scanning electron microscopy (SEM), real-time PCR, Western blotting, and DMMB analysis. The results demonstrated that the silk microfibers exhibited a higher proliferative cell rate over time compared to the PCL microfibers. Additionally, the expression of chondrogenic phenotypes was significantly upregulated, while the marker for hypertrophic chondrocytes—type X collagen—was downregulated in cell-laden silk microfibers compared to cell-laden PCL microfibers. These findings suggest that natural degummed silk microfibers may be a viable option for repairing damaged cartilage in the future of orthopedic surgery and bioengineering. Full article

Spider silk proteins (spidroins) have garnered attention in biomaterials research due to their ability to self-assemble into hydrogels. However, reported spidroin hydrogels require high protein concentration and prolonged gelation time. Our study engineered an artificial spidroin that exhibits unprecedented rapid self-assembly into hydrogels at physiologically relevant conditions, achieving gelation at a low concentration of 6 mg/mL at 37 °C without external additives. Remarkably, at a 30 mg/mL concentration, our engineered protein forms hydrogels within 30 s, a feature we termed “superfast gelation”. This rapid formation is modulated by ions, pH, and temperature, offering versatility in biomedical applications. The hydrogel’s capacity to encapsulate proteins and support E. coli growth while inducing RFP expression provides a novel platform for drug delivery and bioengineering applications. Our findings introduce a superfast, highly adaptable, and cytocompatible hydrogel that self-assembles under mild conditions, underscoring the practical implication of rapid gelation in biomedical research and clinical applications. Full article

The design of hydrogels that combine both the biochemical cues needed to direct seeded cellular functions and mineralization to provide the structural and mechanical properties approaching those of mineralized native bone extracellular matrix (ECM) represents a significant challenge in bone tissue engineering. While fibrous hydrogels constituting of collagen or fibrin (and their hybrids) can be considered as scaffolds that mimic to some degree native bone ECM, their insufficient mechanical properties limit their application. In the present study, an automated gel aspiration–ejection (automated GAE) method was used to generate collagen–fibrin hybrid gel scaffolds with micro-architectures and mechanical properties approaching those of native bone ECM. Moreover, the functionalization of these hybrid scaffolds with negatively charged silk sericin accelerated their mineralization under acellular conditions in simulated body fluid and modulated the proliferation and osteoblastic differentiation of seeded MC3T3-E1 pre-osteoblastic cells. In the latter case, alkaline phosphatase activity measurements indicated that the hybrid gel scaffolds with seeded cells showed accelerated osteoblastic differentiation, which in turn led to increased matrix mineralization. In summary, the design of dense collagen–fibrin hybrid gels through an automated GAE process can provide a route to tailoring specific biochemical and mechanical properties to different types of bone ECM-like scaffolds, and can provide a model to better understand cell–matrix interactions in vitro for bioengineering purposes. Full article

Limbal stem cells (LSCs) are of paramount importance in corneal epithelial tissue repair. The cornea becomes opaque in case of limbal stem cell deficiency (LSCD), which may cause serious damage to the ocular visual function. There are many techniques to restore damaged epithelium, one of which is the transplantation of healthy cultured LSCs, usually onto a human amniotic membrane or onto bio-based engineered scaffolds in recent years. In this study, melt electrospun polylactic acid (PLA) was modified by silk fibroin or gelatin and further cultured with LSCs originating from three different donors. In terms of physicochemical properties, both modifications slightly increased PLA scaffold porosity (with a significantly larger pore area for the PLA/gelatin) and improved the scaffolds’ swelling percentage, as well as their biodegradation rate. In terms of the scaffold application function, the aim was to detect/visualize whether LSCs adhered to the scaffolds and to further determine cell viability (total number), as well as to observe p63 and CK3 expressions in the LSCs. LSCs were attached to the surface of microfibers, showing flattened conformations or 3D spheres in the formation of colonies or agglomerations, respectively. All scaffolds showed the ability to bind the cells onto the surface of individual microfibers (PLA and PLA/gelatin), or in between the microfibers (PLA/silk fibroin), with the latter showing the most intense red fluorescence of the stained cells. All scaffolds proved to be biocompatible, while the PLA/silk fibroin scaffolds showed the highest 98% viability of 2.9 × 10⁶ LSCs, with more than 98% of p63 and less than 20% of CK3 expressions in the LSCs, thus confirming the support of their growth, proliferation and corneal epithelial differentiation. The results show the potential of these bio-engineered scaffolds to be used as an alternative clinical approach. Full article

There is a need to develop the next generation of medical products that require biomaterials with improved properties. The versatility of various gels has pushed them to the forefront of biomaterials research. Cryogels, a type of gel scaffold made by controlled crosslinking under subzero or freezing temperatures, have great potential to address many current challenges. Unlike their hydrogel counterparts, which are also able to hold large amounts of biologically relevant fluids such as water, cryogels are often characterized by highly dense and crosslinked polymer walls, macroporous structures, and often improved properties. Recently, one biomaterial that has garnered a lot of interest for cryogel fabrication is silk and its derivatives. In this review, we provide a brief overview of silk-based biomaterials and how cryogelation can be used for novel scaffold design. We discuss how various parameters and fabrication strategies can be used to tune the properties of silk-based biomaterials. Finally, we discuss specific biomedical applications of silk-based biomaterials. Ultimately, we aim to demonstrate how the latest advances in silk-based cryogel scaffolds can be used to address challenges in numerous bioengineering disciplines. Full article

The Antheraea Pernyi silk gland protein originates from natural organisms and synthesized by tussah silk glands and has widely potential biomaterial applications due to the superior biocompatibility. This study investigates the Antheraea Pernyi silk gland protein-based drug-loaded bio-hydrogels for bioengineered tissue fabricated by using an eco-friendly method without the harsh extracting process and the usage of toxic chemicals. The drug-loaded bio-hydrogels exhibited a porous structure and interconnected pore walls. The swelling ratio and water absorption of drug-loaded bio-hydrogels were, respectively, above 95% and 1.5 × 10³%. The cumulative release of drug loaded hydrogels all reached more than 90% within 4 h, and this indicates the potential of drug-loaded hydrogels as future drug-carrying biomaterials. RSC96 Schwann cells cultured on drug-loaded hydrogels for 72 h under cell culture medium show no toxic effects and more pro-proliferative effects. The results suggest the suitability of drug-loaded bio-hydrogels as natural biopolymer for the potential in vitro RSC96 cell culture platform and other biomaterial applications. Full article

Due to the excellent biocompatibility of natural polymers, a variety of natural polymers have been widely used as biomaterials for manufacturing tissue engineered scaffolds. Despite the excellent biological activity of natural polymers, there have been obstacles in using them on their own to prepare 3D scaffolds with sufficient mechanical strength. Although multiple 3D-bioprinting technologies have recently emerged as effective manufacturing tools for scaffold preparation, scaffold preparation using only natural polymers with tunable mechanical properties is still difficult. Herein, we introduce novel scaffold fabrication methods using the natural polymer silk fibroin via indirect 3D-bioprinting technology. The developed silk fibroin scaffolds showed biocompatibility and tunable mechanical strength by changing the concentration of the silk fibroin. Furthermore, controlling the flexibility of the silk fibroin scaffolds was made possible by changing the solvent for the silk fibroin solution used to fabricate the scaffold. Consequently, silk fibroin scaffolds fabricated via our method can be considered for various applications in the bioengineering of either soft or musculoskeletal tissues. Full article

Although progress is observed in cancer treatment, this disease continues to be the second leading cause of death worldwide. The current understanding of cancer indicates that treating cancer should not be limited to killing cancer cells alone, but that the target is the complex tumor microenvironment (TME). The application of nanoparticle-based drug delivery systems (DDS) can not only target cancer cells and TME, but also simultaneously resolve the severe side effects of various cancer treatment approaches, leading to more effective, precise, and less invasive therapy. Nanoparticles based on proteins derived from silkworms’ cocoons (like silk fibroin and sericins) and silk proteins from spiders (spidroins) are intensively explored not only in the oncology field. This natural-derived material offer biocompatibility, biodegradability, and simplicity of preparation methods. The protein-based material can be tailored for size, stability, drug loading/release kinetics, and functionalized with targeting ligands. This review summarizes the current status of drug delivery systems’ development based on proteins derived from silk fibroin, sericins, and spidroins, which application is focused on systemic cancer treatment. The nanoparticles that deliver chemotherapeutics, nucleic acid-based therapeutics, natural-derived agents, therapeutic proteins or peptides, inorganic compounds, as well as photosensitive molecules, are introduced. Full article