Silk Fibroin Hydrogels Research Articles

Comparison of Silk Hydrogels Prepared via Different Methods.

Silk fibroin (SF) hydrogels have garnered extensive attention in biomedical materials, owing to their superior biological properties. However, the challenges facing the targeted silk fibroin hydrogels involve chemical agents and shortfalls in performance. In this study, the silk fibroin hydrogels were prepared in different ways: sonication induction, chemical crosslinking, photopolymerization, and enzyme-catalyzed crosslinking. The SF hydrogels derived from photopolymerization exhibited higher compressive properties, with 124 Kpa fracture compressive stress and breaks at about 46% compression. The chemical crosslinking and enzyme-catalyzed silk fibroin hydrogels showed superior toughness, yet sonication-induced hydrogels showed brittle performance resulting from an increase in silk II crystals. The chemical-crosslinked hydrogel demonstrated lower thermostability due to the weaker crosslinking degree. In vitro, all silk fibroin hydrogels supported the growth of human umbilical vein endothelial cells, as the cell viability of hydrogels without chemical agents was relatively higher. This study provides insights into the formation process of silk fibroin hydrogels and optimizes their design strategy for biomedical applications.

Antibacterial-Antioxidative Thiolated Gelatin/Methacrylated Silk Fibroin Hydrogels with Nitric Oxide Release Catalyzed by Metal-Polyphenol Nanoparticles for MRSA-Infected Wound Healing.

Chronic wound infection often leads to irregular tissue closure and accompanies delayed healing and economy issues. Developing an ideal wound dressing that can control the occurrence of antibacterial infections and biological responses is highly desirable. In this study, a multifunctional hybrid hydrogel (GS@EG-Cu-CA NPs) containing synthesized thiolated gelatin, methacrylated silk fibroin, and (-)-epigallocatechin gallate-copper ionic-carrageenan nanoparticles (EG-Cu-CA NPs) was engineered by a thio-ene click reaction. The metal-polyphenol EG-Cu-CA NPs were encapsulated with kappa-carrageenan to enhance its aqueous-soluble, mechanical, and bioactive properties and endowed the hydrogel dressing with fascinating antibacterial, antioxidation, and nitric oxide (NO) generation by catalyzing. The hybrid hydrogels also illustrated a favorable cytocompatibility. Benefiting from the thio-ene click reaction, the hybrid hydrogels were injected and photocured rapidly in situ to cover an irregular wound. In an SD rat full-thickness skin-wound-infected model, the methicillin-resistant Staphylococcus aureus-infected wound covered with GS@EG-Cu-CA NPs was almost completely healed after 10 days. This study presents a facile design of hydrogel dressing incorporating metal-polyphenol nanoparticles, which demonstrates a promising potential way for dealing with effective wound infection management and other complicated wound healings.

Glucose-Responsive Self-Regulated Injectable Silk Fibroin Hydrogel for Controlled Insulin Delivery.

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we present a glucose-responsive smart hydrogel platform based on phenylboronic acid-functionalized natural silk fibroin protein for regulated insulin delivery. The modified protein was synergistically self-assembled and cross-linked through β-sheet and phenylboronate ester formation. The dynamic nature of the bonding confers smooth injectability through the needle. The cross-linked hydrogel structures firmly hold the glucose-sensing element and insulin in its pores and contribute to long-term sensing and drug storage. Under hyperglycemic conditions, the hydrogen peroxide generated from the sensing element induces hydrogel matrix degradation by oxidative cleavage, enabling insulin release. In vivo studies in a type 1 diabetic Wistar rat model revealed that the controlled insulin release from the hydrogel restored diabetic glucose level to physiological conditions for 36 h. This work establishes the functional modification of silk fibroin into a glucose-responsive hydrogel platform for regulated and functional insulin delivery application.

Encapsulation of Sericin-Decorated Efficient Agents in Silk Hydrogels for Wound Dressings.

Excessive oxidative stress, bacterial infections, and inflammation are the primary factors impeding the healing of skin wounds. Bioactive hydrogels are commonly employed in the treatment of skin injuries. However, the limited solubility of many drugs and active agents in water significantly hampers their effectiveness in hydrogel dressings. In this research, prior to incorporation into the silk fibroin (SF) hydrogel matrix, two active agents curcumin and silver nanoparticles (Ag NPs) were decorated by silk sericin to improve their dispersibility and stability in water. The resultant SF/Ag/C hydrogels combined the biological safety and nontoxicity of SF, the antioxidant and anti-inflammatory efficacy of curcumin, and the antibacterial effect of Ag NPs. These properties effectively enhanced wound repair by reducing bacterial infections, mitigating oxidative stress, suppressing the expression of pro-inflammatory factors, and promoting angiogenesis. This study presented a straightforward approach for constructing bioactive hydrogels for the promotion of the wound healing process.

Fabrication of green composite hand knitted silk mesh reinforced with silk hydrogel

Soft tissue defects like hernia and post-surgical fistula formation can be resolved with modern biomaterials in the form of meshes without post-operative complications. In the present study hand knitted silk meshes were surface coated with regenerated silk fibroin hydrogel and pure natural extracts. Two phytochemicals (Licorice extract (LE) and Bearberry extract (BE)) and the two honeybee products (royal jelly (RJ) and honey (HE)) were incorporated separately to induce antibacterial, anti-inflammatory, and wound healing ability to the silk hydrogel coated knitted silk meshes. Meshes were dip coated with a blend of 4 % silk hydrogel (w/v) and 5 % extracts. Dried modified meshes were characterized using SEM, DMA, GC–MS and FTIR. Antimicrobial testing, in-vitro cytotoxicity, in-vitro wound healing and Q-RT-PCR were also performed.SEM analysis concluded that presence of coating reduced the pore size up to 47.7 % whereas, fiber diameter was increased up to 17.9 % as compared to the control. The presence of coating on the mesh improved the mechanical strength/Young's modulus by 1602.8 %, UTS by 451.7 % and reduced the % strain by 51.12 %. Sustained release of extracts from MHRJ (62.9 % up to 72 h) confirmed that it can induce antibacterial activity against surgical infections. Cytocompatibility testing and gene expression results suggest that out of four variables MHRJ presented best cell viability, % wound closure and expression of wound healing marker genes. In-vivo analyses in rat hernia model were carried out using only MHRJ variant, which also confirmed the non- toxic nature and wound healing characteristics of the modified mesh. The improved cell proliferation and activated wound healing in vitro and in vivo suggested that MHRJ could be a valuable candidate to promote cell infiltration and activate soft tissue and hernia repair as a biomedical implant.

Silk fibroin hydrogel membranes prepared by a sequential cross-linking strategy for guided bone regeneration

Silk fibroin hydrogel is a widely used material for tissue engineering. However, its mechanical properties are the main obstacle to its application to medical bone regeneration barrier membranes. Here, we developed a new hydrogel membrane for guided bone regeneration (GBR). In this study, a sequential crosslinking strategy including photo crosslinking and organic solvent (ethanol) treatment was used to obtain silk fibroin hydrogel membrane (EA-SF). The mechanical properties of EA-SF were significantly enhanced compared to the hydrogel prepared only by photocrosslinking (E-SF). The compressive and tensile strengths of the hydrogel film treated with 75% ethanol for 6 h were 1.18 ± 0.36 MPa and 0.43 ± 0.03 MPa, respectively. In vitro cell culture results showed that EA-SF has good biocompatibility and can effectively shield fibroblasts (L929). EA-SF also has excellent in vitro protein hydrolysis stability. In vivo experiments (subcutaneous implantation and calvarial defect experiment) confirmed the stability and barrier functionality of EA-SF. In conclusion, this study demonstrated that ethanol could improve the mechanical properties of silk fibroin hydrogel and extend the scope of their application, making silk fibroin hydrogel a promising GBR material.

Tough silk fibroin hydrogel via polypropylene glycol (PPG) blending for wearable sensors

AbstractRegenerated silk fibroin is a promising bio‐material because of its sustainability, biocompatibility, degradability, and eco‐friendliness. However, silk fibroin hydrogel's intrinsic hard and brittle mechanical properties hinder its application on human skin as a wearable sensor. We used polypropylene glycol (PPG) as a plasticizer to physically blend with a silk fibroin solution, and designed a set of green and environmentally friendly preparation methods without organic solvents to obtain the hydrogel for wearable sensors. PPG molecules will aggregate into clusters to act as a plasticizer. Meanwhile, a large number of hydrogen bonds are formed between the hydroxyl groups in PPG and silk fibroin molecular chains. When the hydrogel is stretched, the hydrogen bond in the silk fibroin chain will release heat in an irreversible form to increase the toughness. The PPG/silk fibroin hydrogel exhibits mechanical strength of 16.6 MPa, breaking elongation of 160%, and toughness of 17.7 MJ/m3. The Ca2+ introduced during the sample preparation process gives the hydrogel ionic conductivity, which provides the possibility of using the hydrogel as a human skin sensing material.

Hydrogelation of Regenerated Silk Fibroin via Gamma Irradiation.

Gamma irradiation, which is one of the more conventional sterilization methods, was used to induce the hydrogelation of silk fibroin in this study. The physical and chemical characteristics of the irradiation-induced silk fibroin hydrogels were investigated. Silk fibroin solution with a concentration greater than 1 wt% formed hydrogel when irradiated by gamma rays at a dose of 25 or 50 kGy. The hydrogel induced by 50 kGy of radiation was more thermally stable at 80 °C than those induced by 25 kGy of radiation. When compared to the spontaneously formed hydrogels, the irradiated hydrogels contained a greater fraction of random coils and a lower fraction of β-sheets. This finding implies that gelation via gamma irradiation occurs via other processes, in addition to crystalline β-sheet formation, which is a well-established mechanism. Our observation suggests that crosslinking and chain scission via gamma irradiation could occur in parallel with the β-sheet formation. The irradiation-induced hydrogels were obtained when the solution concentration was adequate to support the radiation crosslinking of the silk fibroin chains. This work has, therefore, demonstrated that gamma irradiation can be employed as an alternative method to produce chemical-free, random coil-rich, and sterilized silk fibroin hydrogels for biomedical applications.

Nacre-inspired, strong, tough silk fibroin hydrogels based on biomineralization and the layer-by-layer assembly of ordered silk fabric

Hydrogels are attractive materials with structures and functional properties similar to biological tissues and widely used in biomedical engineering. However, traditional synthetic hydrogels possess poor mechanical strength, and their applications are limited. Herein, a multidimensional material design method is developed; it includes the in situ gelation of silk fabric and nacre-inspired layer-by-layer assembly, which is used to prepare silk fibroin (SF) hydrogels. The in situ gelation method of silk fabric introduces a directionally ordered fabric network in a silk substrate, considerably enhancing the strength of hydrogels. Based on the nacre structure, the layer-by-layer assembly method enables silk hydrogels to break through the size limit and increase the thickness, realizing the longitudinal extension of the hydrogels. The application of the combined biomineralization and hot pressing method can effectively reduce interface defects and improve the interaction between organic and inorganic interfaces. The multidimensional material design method helps increase the strength (287.78 MPa), toughness (18.43 MJ m−3), and fracture energy (50.58 kJ m−2) of SF hydrogels; these hydrogels can weigh 2000 times their own weight. Therefore, SF hydrogels designed using the aforementioned combined method can realize the combination of strength and toughness and be used in biological tissue engineering and structural materials.

Research on Silk Fibroin Biomaterials for Wound Dressing

With the development of the times, biology and textile technology industry has been greatly promoted. Domestic and foreign research focus on silk fibroin gradually shifted from the traditional textile field to the biomedical textiles field .the research on silk fibroin wound dressing is gradually developed, which has a great impact on accelerating wound repair. Studies have shown that the effect of wound repair is closely related to the physical and chemical properties of the raw materials. These characteristics also show that silk can be designed flexibly according to the requirements of dressing. Similarly, the production process of silk fibroin dressings and the association between adhesion and drug delivery also have a great impact. This article will elaborate the performance characteristics, advantages and problems in the research process of silk fibroin dressings, including silk fibroin membrane, silk fibroin hydrogel, silk fibroin scaffold, nanofiber membrane and other materials, as well as some new silk fibroin wound dressings currently under research, and clarify the development direction and outlook of silk fibroin in the future.

Piezoelectric composite hydrogel with wireless electrical stimulation enhances motor functional recovery of spinal cord injury

Electrical stimulation (ES) can restore motor function after spinal cord injury (SCI). However, traditional intraspinal ES has many disadvantages, such as the need for a complex circuitry device, an external power source, and a second surgery to remove the implant. Piezoelectric materials have received increasing attention due to their potential to convert ambient mechanical energy into ES without an external power source or implantation of electrodes. Herein, a novel polydopamine (PDA) coated barium titanate (BaTiO3) nanoparticles (BaTiO3@PDA) incorporated silk fibroin (SF) hydrogel (SFBT) was established. The SFBT hydrogel was crosslinked by horseradish peroxidase (HRP)/hydrogel peroxide (H2O2) to integrate the piezoelectric potency of BaTiO3 with the thermal sensitivity of HRP/H2O2 for SCI recovery. The hydrogel containing 5% (w/v) BaTiO3@PDA nanoparticles (SFBT-5), which was selected for in vivo study, exhibited a short gelation time (5 min), suitable storage modulus (925 ± 35 Pa), and wireless ES (average current of 124 nA). Moreover, Basso-Beattie-Bresnahan (BBB) scores test and footprint analysis demonstrated that the SFBT-5 hydrogel successfully enhanced motor functional recovery of SCI. In histopathological assessments, the SFBT-5 hydrogel significantly accelerated spinal cord healing, as indicated by smaller lesion cavities (∼16.7% of the SCI group). Meanwhile, the SFBT-5 hydrogel accelerated neurogenesis, facilitated axon regrowth and synapse formation, and promoted remyelination. Overall, this study highlights the potential of piezoelectric hydrogels for SCI regeneration.

Highly Stable CuS Nanotrough‐Networks Constructed on Arbitrate Substrate for Flexible Supercapacitor

Herein, supercapacitors (SC) are fabricated on arbitrary flexible substrates by constructing copper sulfide nanotrough‐network and electrodeposition of polyaniline (PANI@CuS NN) as electrode. Attributed to its unique hollow structure, the CuS NN current collector demonstrates high conductivity (10.4 Ω □−1) and mechanical flexibility (within 2.3% relative resistance change after more than 1,000 bending times at the radius of 4 mm). The obtained PANI@CuS NN electrode demonstrates more than 218.28 F g−1 specific capacity at the current density of 1 A g−1, remaining 85.08% of the original capacity after 1,000 cycles (5 A g−1). This can be attributed to that CuS NN provides abundant attachment sites for PANI by the large specific surface area. Additionally, a flexible solid‐state supercapacitor is constructed by coating silk fibroin hydrogel as the electrolyte between the PANI@CuS NN and another CuS NN electrode loaded with multiwalled carbon nanotubes (MWCNTs@CuS NN). The capacity is 107.8 F g−1 at the current density of 0.25 A g−1 with excellent cycling stability.

Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low-Concentration Collagen-Based Bioinks.

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low-concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized with a thermoresponsive hyaluronic acid-based polymer to maintain the phenotypes of both the noninvasive epithelial and invasive breast cancer cells, as well as cancer-associated fibroblasts. Mouse breast tumor organoids are bioprinted using optimized collagen bioink to mimic in vivo tumor morphology. A vascularized tumor model is also created using a similar strategy, with significantly enhanced vasculature formation under hypoxia. This study shows the great potential of embedded bioprinted breast tumor models utilizing a low-concentration collagen-based bioink for advancing the understanding of tumor cell biology and facilitating drug discovery research.

Applications of Tissue Engineering in Meniscus Repair

Knee meniscus injury has a high incidence, which can change the load-bearing structure of the knee joint, causing pain and further cartilage damage and osteoarthritis and other related diseases, and is difficult to prevent and treat effectively. Therefore, how to treat meniscus injury has become one of the hot issues concerned by patients and medical staff in recent years. Compared with simple meniscectomy, tissue engineering meniscectomy has fewer adverse effects and some techniques have achieved satisfactory results. At present, the meniscus tissue engineering treatment method is continuously developing and innovating. In this paper, the promising techniques of collagen scaffold implantation, silk fibroin scaffold implantation, hydrogel implantation and bone marrow stimulation were discussed, we hope to provide the basis for the further development of meniscus repair.

Versatile Potential of Photo-Cross-Linkable Silk Fibroin: Roadmap from Chemical Processing Toward Regenerative Medicine and Biofabrication Applications.

Over the past two decades, hydrogels have come to the forefront of tissue engineering and regenerative medicine due to their biocompatibility, tunable degradation and low immunogenicity. Due to their porosity and polymeric network built up, it is possible to incorporate inside drugs, bioactive molecules, or other biochemically active monomers. Among biopolymers used for the fabrication of functional hydrogels, silk fibroin (SF) has received considerable research attention owing to its known biocompatibility and tunable range of mechanical properties. However, its relatively simple structure limits the potential usability. One of the emerging strategies is a chemical functionalization of SF, allowing for the introduction of methacrylate groups. This allows the versatile processing capability, including photo-cross-linking, which makes SF a useful polymer as a bioink for 3D printing. The methacrylation reaction has been done using numerous monomers such as methacrylic anhydride (MA), 2-isocyanatoethyl methacrylate (IEM), or glycidyl methacrylate (GMA). In this Review, we summarize the chemical functionalization strategies of SF materials and their resulting physicochemical properties. More specifically, a brief explanation of the different functionalization methods, the cross-linking principles, possibilities, and limitations of methacrylate compound functionalization are provided. In addition, we describe types of functional SF hydrogels and link their design principles to the performance in applications in the broad fields of biofabrication, tissue engineering, and regenerative medicine. We anticipate that the provided guidelines will contribute to the future development of SF hydrogels and their composites by providing the rational design of new mechanisms linked to the successful realization of targeted biomedical application.

Long-Lasting Thixotropic Natural Polymeric Hydrogel Based on Silk Nanofibrils.

Hydrogels are considered to be ideal biomedical materials as their physical properties are similar to the physiological tissue environment. In particular, thixotropic hydrogels have received increasing attention from researchers because of their injectability. Herein, a simple and rapid method was developed for the preparation of a regenerated silk fibroin (RSF) hydrogel with long-lasting and excellent thixotropy. The thixotropic RSF hydrogel was readily formed by ultrasonic treatment of the pretreated RSF solution for 2 min followed by incubation at 40 °C for 10 min. The storage modulus of the RSF hydrogels recovered to more than 90% of the original value within 20 s after withstanding 1000% shear strain. By avoiding complicated chemical or physical treatments and by addition of crosslinking agents and/or other chemical components, the obtained RSF hydrogels maintained excellent biocompatibility. Hence, the cells implanted inside the hydrogel can grow and proliferate normally. By virtue of ultrasonic treatment during the preparation, functional nanoparticles can be uniformly dispersed in the RSF solution to prepare RSF-based hybrid hydrogels with various functions. As an application example, hydroxyapatite (HAP) with osteoinductivity was mixed with RSF solution to prepare the RSF/HAP hybrid hydrogel. The RSF/HAP hybrid hydrogel maintained biocompatibility and thixotropy of the original RSF hydrogel and promoted osteoblastic differentiation of cells owing to the addition of HAP. Therefore, the RSF hydrogel prepared in this work has a strong application prospect in the biomedical field including, but not limited to, bone repair.

Harnessing immunomodulation for efficient bone Regeneration: Bioengineered black phosphorus-incorporated Self-Healing hydrogel

Osteoimmunology and immune microenvironments play an important role in bone tissue regeneration. Efficient and timely activation of pro-regenerative macrophages (M2) at the early stage is significant for new bone formation. In this study, an M2 phenotype-enabled multifunction hydrogel for efficient bone regeneration was developed. A layer of tannic acid (TA)-Mg2+ chelate networks were coated on black phosphorus (BP) nanosheets via a simple one-step method. TA-Mg2+ chelate on BP improves the stability of BP and enhances the osteogenesis and osteoimmunomodulation ability of BP. In addition, TA-Mg2+ modification also enhances interfacial bonding between BP nanosheets and the hydrogel matrix. Introducing BP@TA-Mg into methacrylate silk fibroin (SFMA) hydrogel can significantly enhance the mechanical capacity and the biological activity. The resulting SFMA–BP@TA-Mg (SFBTM) hydrogel exhibits the potential to polarize macrophages towards M2 phenotype, enhance angiogenesis in human umbilical vein endothelial cells (HUVECs), and promote osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs). In vivo results demonstrate that the SFBTM hydrogel significantly enhances bone regeneration by modulating the immune microenvironment and macrophage phenotype, thereby promoting the vascularization and bone regeneration at the site of bone defects. This study provides a new perspective for critical-sized bone defect treatment through immunomodulation bioactive materials.

Evaluation of new robust silk fibroin hydrogels for posterior scleral reinforcement in rabbits.

Background: Currently, there is no ideal material available for posterior scleral reinforcement (PSR) to prevent the progression of high myopia. In this study, we investigated robust regenerated silk fibroin (RSF) hydrogels as potential grafts for PSR in animal experiments to evaluate their safety and biological reactions. Methods: PSR surgery was performed on the right eye of twenty-eight adult New Zealand white rabbits, with the left eye serving as a self-control. Ten rabbits were observed for 3 months, while 18 rabbits were observed for 6 months. The rabbits were evaluated using intraocular pressure (IOP), anterior segment and fundus photography, A- and B-ultrasound, optical coherence tomography (OCT), histology, and biomechanical tests. Results: No complications such as significant IOP fluctuation, anterior chamber inflammation, vitreous opacity, retinal lesion, infection, or material exposure were observed. Furthermore, no evidence of pathological changes in the optic nerve and retina, or structural abnormalities on OCT, were found. The RSF grafts were appropriately located at the posterior sclera and enclosed in fibrous capsules. The scleral thickness and collagen fiber content of the treated eyes increased after surgery. The ultimate stress of the reinforced sclera increased by 30.7%, and the elastic modulus increased by 33.0% compared to those of the control eyes at 6months after surgery. Conclusion: Robust RSF hydrogels exhibited good biocompatibility and promoted the formation of fibrous capsules at the posterior sclera in vivo. The biomechanical properties of the reinforced sclera were strengthened. These findings suggest that RSF hydrogel is a potential material for PSR.

Resistance to Degradation of Silk Fibroin Hydrogels Exposed to Neuroinflammatory Environments.

Central nervous system (CNS) diseases represent an extreme burden with significant social and economic costs. A common link in most brain pathologies is the appearance of inflammatory components that can jeopardize the stability of the implanted biomaterials and the effectiveness of therapies. Different silk fibroin scaffolds have been used in applications related to CNS disorders. Although some studies have analyzed the degradability of silk fibroin in non-cerebral tissues (almost exclusively upon non-inflammatory conditions), the stability of silk hydrogel scaffolds in the inflammatory nervous system has not been studied in depth. In this study, the stability of silk fibroin hydrogels exposed to different neuroinflammatory contexts has been explored using an in vitro microglial cell culture and two in vivo pathological models of cerebral stroke and Alzheimer's disease. This biomaterial was relatively stable and did not show signs of extensive degradation across time after implantation and during two weeks of in vivo analysis. This finding contrasted with the rapid degradation observed under the same in vivo conditions for other natural materials such as collagen. Our results support the suitability of silk fibroin hydrogels for intracerebral applications and highlight the potentiality of this vehicle for the release of molecules and cells for acute and chronic treatments in cerebral pathologies.

Application of Silk-Fibroin-Based Hydrogels in Tissue Engineering

Silk fibroin (SF) is an excellent protein-based biomaterial produced by the degumming and purification of silk from cocoons of the Bombyx mori through alkali or enzymatic treatments. SF exhibits excellent biological properties, such as mechanical properties, biocompatibility, biodegradability, bioabsorbability, low immunogenicity, and tunability, making it a versatile material widely applied in biological fields, particularly in tissue engineering. In tissue engineering, SF is often fabricated into hydrogel form, with the advantages of added materials. SF hydrogels have mostly been studied for their use in tissue regeneration by enhancing cell activity at the tissue defect site or counteracting tissue-damage-related factors. This review focuses on SF hydrogels, firstly summarizing the fabrication and properties of SF and SF hydrogels and then detailing the regenerative effects of SF hydrogels as scaffolds in cartilage, bone, skin, cornea, teeth, and eardrum in recent years.