Silk Fibroin Hydrogels Research Articles

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.

Effect of plasma jet on electrochemical properties of silk fibroin hydrogel doped with PEDOT:PSS

AbstractIn this study, by injecting cold plasma into the silk fibroin (SF) solution, and adding poly (3,4‐ethylenedioxythiophene): polystyrene sulfonic acid (PEDOT:PSS) into the SF solution, the conductive SF‐PEDOT:PSS hydrogel modified by plasma was successfully prepared. The changes of the electrochemical parameters and structure of SF‐PEDOT:PSS hydrogels after plasma modification were observed with plasma discharge time (60, 120, 180 s) and the type of working gas (Ar, air, He) as variables. The results of electrochemical impedance spectroscopy show that both argon plasma and helium plasma can reduce the impedance of SF‐PEDOT:PSS hydrogel in the extremely low‐frequency range (10−2–10° Hz), and a longer discharge time shrinks the impedance, while the impact of air plasma on the impedance of hydrogel is not obvious. The capacitance results show that both argon and helium plasma can make the capacitance of hydrogel larger, and the longer discharge time leads to the larger capacitance. While air plasma can reduce the capacitance of hydrogel. The results of Fourier infrared absorption spectroscopy and X‐ray diffraction spectrum show that the secondary structure of SF is mainly β‐fold. The results of Raman show that PEDOT:PSS is successfully incorporated into hydrogel, and there exists random coil conformation of SF in hydrogel. The results of X‐ray photoelectron spectroscopy show that the SF‐PEDOT:PSS hydrogel mainly contains C, O, and N elements.

Chondrogenic Differentiation of Adipose-Derived Stromal Cells Induced by Decellularized Cartilage Matrix/Silk Fibroin Secondary Crosslinking Hydrogel Scaffolds with a Three-Dimensional Microstructure.

Finding an ideal scaffold is always an important issue in the field of cartilage tissue engineering. Both decellularized extracellular matrix and silk fibroin have been used as natural biomaterials for tissue regeneration. In this study, a secondary crosslinking method of γ irradiation and ethanol induction was used to prepare decellularized cartilage extracellular matrix and silk fibroin (dECM-SF) hydrogels with biological activity. Furthermore, the dECM-SF hydrogels were cast in custom-designed molds to produce a three-dimensional multi-channeled structure to improve internal connectivity. The adipose-derived stromal cells (ADSC) were seeded on the scaffolds, cultured in vitro for 2 weeks, and implanted in vivo for another 4 and 12 weeks. The double crosslinked dECM-SF hydrogels exhibited an excellent pore structure after lyophilization. The multi-channeled hydrogel scaffold presents higher water absorption ability, surface wettability, and no cytotoxicity. The addition of dECM and a channeled structure could promote chondrogenic differentiation of ADSC and engineered cartilage formation, confirmed by H&E, safranin O staining, type II collagen immunostaining, and qPCR assay. In conclusion, the hydrogel scaffold fabricated by the secondary crosslinking method has good plasticity and can be used as a scaffold for cartilage tissue engineering. The multi-channeled dECM-SF hydrogel scaffolds possess a chondrogenic induction activity that promotes engineered cartilage regeneration of ADSC in vivo.

Silk fibroin hydrogel: A novel biopolymer for sustained release of vancomycin drug for diabetic wound healing

Diabetic wounds are a global concern due to their sluggish healing and likely to develop bacterial infections. In the current study, we prepared silk fibroin (SF) hydrogel and a composite of vancomycin (VANCO) - loaded SF hydrogel. SEM, swelling behavior, biodegradability, spreadability, viscosity analysis, infrared analysis (FTIR), and 1H NMR spectroscopy were used to characterize the composites and SF hydrogel. In addition, in vitro, in vivo, and serum analyses have been carried out. The results of SEM analysis, FTIR, and 1H NMR spectroscopy confirmed the successful encapsulation of SF hydrogel and VANCO. Whereas, in-vitro research demonstrated the controlled drug release and antibacterial ability of VANCO-loaded SF hydrogel composite. An in-vivo study revealed that a composite of VANCO-loaded SF hydrogel performed better than SF hydrogel and povidone (antiseptic cream), with diabetic wound healing percentages of 86.66, 33.33 and 16.66%, respectively. Further, serum analysis confirmed that in the composite treated group, metabolites such as lactate, serine, taurine, and others had been significantly increased, which have been directly correlated to wound healing. As a result, our composites have significant potential as antiseptic gels for diabetic wound healing.

Regenerated silk fibroin and alginate composite hydrogel dressings loaded with curcumin nanoparticles for bacterial-infected wound closure

It is important to treat a bacterial-infected wound with a hydrogel dressing due to its excellent biocompatibility and extracellular matrix mimicking structure. In this work, the antibacterial curcumin nanoparticles (Cur-NPs) loaded silk fibroin and sodium alginate (SF/SA) composite hydrogels have been developed as dressings for bacterial-infected wound closure. The as-prepared composite hydrogel dressings exhibited excellent biocompatibility and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, the composite hydrogel dressings showed good tissue adhesive strength because of their high viscosity and abundance of amino groups distributed on SF, which can form multi-aldehyde polysaccharides with the tissue surface. The porous 3D structure of the composite hydrogel dressings facilitated the absorption of exudate from the wound site and promoted the fusion of cellular nutrients and metabolites. In the full-thickness skin defect model with and without bacterial infection, the Cur-NPs loaded SF/SA composite hydrogel dressings prominently improves the closure of bacterial-infected wounds by improving cell proliferation, anti-inflammatory properties, vascular remodeling, and collagen deposition.

Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis

Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.

Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy.

Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150 [Formula: see text]g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30 [Formula: see text]g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience. Schematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice.

3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability.

Biological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coordinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and materials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and metachronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable metachronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical engineering, and biocompatible implants.

Silk Fibroin Hydrogel-Assisted Controlled Release of Antifungal Drug Ketoconazole

This research focused on preparing a ketoconazole-infused silk fibroin hydrogel to enhance patient compliance, leveraging the hydrogel's biocompatibility and biodegradability. The process used a 50% (v/v) ethanol, propanol, or glycerol solution treated with 2% (w/v) silk fibroin at 37°C. The use of glycerol quickened the gelation process. The hydrogel's structure was analyzed via SEM, and UV-VIS spectrometry was used to evaluate the encapsulation efficiency and ketoconazole release profile. The surface structure varied based on the formulation and the best encapsulation efficiency was observed with ethanol (60±1.78%), followed by propanol (56±2.72%) and glycerol (47±1.42%). The release profile demonstrated an initial burst release followed by 20 hours of sustained release. Furthermore, the hydrogel-encapsulated drug demonstrated effective antifungal activity against Aspergillus Niger. As a result, silk fibroin hydrogels are a promising option for controlled topical delivery of ketoconazole.
 Keywords: Silk fibroin, Controlled release, Hydrogels, Drug delivery.

Silk Fibroin-Based Shape-Memory Organohydrogels with Semicrystalline Microinclusions.

Inspired by nature, we designed organohydrogels (OHGs) consisting of a silk fibroin (SF) hydrogel as the continuous phase and the hydrophobic microinclusions based on semicrystalline poly(n-octadecyl acrylate) (PC18A) as the dispersed phase. SF acts as a self-emulsifier to obtain oil-in-water emulsions, and hence, it is a versatile and green alternative to chemical emulsifiers. We first prepared a stable oil-in-water emulsion without an external emulsifier by dispersing the n-octadecyl acrylate (C18A) monomer in an aqueous SF solution. To stabilize the emulsions for longer times, gelation in the continuous SF phase was induced by the addition of ethanol, which is known to trigger the conformational transition in SF from random coil to β-sheet structures. In the second step, in situ polymerization of C18A droplets in the emulsion system was conducted under UV light in the presence of a photoinitiator to obtain high-strength OHGs with shape-memory function, and good cytocompatibility. The incorporation of hydrophilic N,N-dimethylacrylamide and noncrystallizable hydrophobic lauryl methacrylate units in the hydrogel and organogel phases of OHGs, respectively, further improved their mechanical and shape-memory properties. The shape-memory OHGs presented here exhibit switchable viscoelasticity and mechanics, a high Young's modulus (up to 4.3 ± 0.1 MPa), compressive strength (up to 2.5 ± 0.1 MPa), and toughness (up to 0.68 MPa).

BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism

Bromodomain-containing protein 9 (BRD9), a component of non-canonical BAF chromatin remodeling complex, has been identified as a critical therapeutic target in hematological diseases. Despite the hematopoietic origin of osteoclasts, the role of BRD9 in osteoclastogenesis and bone diseases remains unresolved. Here, we show Brd9 deficiency in myeloid lineage enhances osteoclast lineage commitment and bone resorption through downregulating interferon-beta (IFN-β) signaling with released constraint on osteoclastogenesis. Notably, we show that BRD9 interacts with transcription factor FOXP1 activating Stat1 transcription and IFN-β signaling thereafter. Besides, function specificity of BRD9 distinguished from BRD4 during osteoclastogenesis has been evaluated. Leveraging advantages of pharmacological modulation of BRD9 and flexible injectable silk fibroin hydrogel, we design a local deliver system for effectively mitigating zoledronate related osteonecrosis of the jaw and alleviating acute bone loss in lipopolysaccharide-induced localized aggressive periodontitis. Overall, these results demonstrate the function of BRD9 in osteoclastogenesis and its therapeutic potential for bone diseases.

Photocurable fisetin silk fibroin hydrogel accelerates infected diabetic wounds healing through biofilm inhibition and macrophage immunomodulation

Infected diabetic wounds (IDW) are difficult to heal and lead to serious complications such as amputation. Inspired by natural elements, we developed an injectable photocurable hydrogel platform based on methacrylamide silk fibroin, encapsulated with ZnO NPs and plants derived fisetin, for accelerating IDW healing. The combined release of ZnO NPs and fisetin inhibited the biofilm formation of Staphylococcus aureus on the wound surface, while fisetin possessed the immunomodulatory function of promoting macrophage M2 polarization and the release of anti-inflammatory cytokines to promote tissue healing. Therefore, this natural hydrogel composite platform can be applied as a potential wound dressing with good biocompatibility.

Construction of adhesive and bioactive silk fibroin hydrogel for treatment of spinal cord injury.

Spinal cord injury (SCI) often causes severe and permanent disabilities due to the complexity of injury progression. The promising methods are generally based on tissue engineering technology using biocompatible hydrogels to achieve SCI repair. However, hydrogels are commonly incapable of close contact with the damaged spinal cord stumps and fail to support neural regeneration in SCI. Therefore, it is still a challenge to achieve stable contact with the transected nerve stumps and accelerate neural regeneration in the lesion microenvironment. Here, an in situ forming glycidyl methacrylated silk fibroin/ laminin-acrylate (SF-GMA/LM-AC) hydrogel was fabricated for SCI repair. The polymer chains formed a network quickly after ultraviolet (UV)-light trigger, in topological entanglement with the spinal cord, stitching the hydrogel and wet tissues together like a suture at the molecular scale. The SF-GMA/LM-AC hydrogel also provided a favorable environment for the growth of cells due to the incorporation of LM-AC. Compared with physical entrapment of LM, LM-AC immobilized in the hydrogel by covalent technology provided better microenvironments for neural stem cells (NSCs) growth. The repair of complete transection SCI in rats demonstrated that this hydrogel guided and promoted neural regeneration over 8 weeks, leading to hind limb locomotion recovery. This adhesive and bioactive SF-GMA/LM-AC hydrogel may open many opportunities in various therapeutic indications, including SCI. STATEMENT OF SIGNIFICANCE: Many materials have been developed for building transplanted scaffolds, but it is still a challenge to fabricate bioactive scaffolds and adhesion to wet tissues. In this study, we successfully developed an in situ forming SF-GMA/LM-AC hydrogel for SCI repair. This in situ forming hydrogel formed significant adhesion to the native spinal cord, stitching hydrogel and tissue together like a suture at the molecular scale. In addition, covalent immobilized LM-AC was used as the contact guidance biochemical cues for axonal outgrowth and had much better bioactive effects than physically entangled LM. Moreover, this universal strategy would open an avenue to fabricate adhesive and bioactive hydrogel for various disease treatments including SCI.

Characterization, antibacterial and anticancer study of silk fibroin hydrogel

Purpose: Protein-based hydrogels such as silk fibroin hydrogel, are used in tissue engineering and regenerative medicine applications as they showed striking characteristics like biocompatibility and offered various benefits as biomaterials. The current study sought to prepare silk fibroin hydrogel and characterise it in order to assess its antibacterial and anticancer activity.
 Methodology: Silk fibroin hydrogel was prepared and characterized by using different microscopy methods, namely Scanning Electron Microscopy (SEM), Phase Contrast Electron (PCM) microscopy, and foldscope analysis. Further, it was characterized through 1H-NMR analysis, Fourier Transform Infrared spectroscopy (FTIR) analysis, and swelling properties. A Current study also covers an antimicrobial and anticancer analysis of silk fibroin hydrogel by disk diffusion method and SRB (Sulforhodamine B) assay respectively.
 Results: The antibacterial study confirmed that SF hydrogel has a moderate antibacterial activity for Streptococcus mutans, and Salmonella typhi. Additionally, the SRB assay test showed that silk fibroin hydrogels had moderate anticancer activity against the human lung cancer cell line (A549).
 Conclusion: The current study unequivocally demonstrates that silk fibroin hydrogel has antibacterial and anti-cancerous properties, making it a suitable scaffold for future studies that seek to target a specific drug delivery site.
 Keywords: Silk fibroin; Swelling behaviour; Anticancer; Drug carrier; Wound healing

Silk fibroin, gelatin, and human placenta extracellular matrix-based composite hydrogels for 3D bioprinting and soft tissue engineering

BackgroundThere is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity.MethodIn this study, silk fibroin (SF) and tyramine-substituted gelatin (G-TA) were enzymatically crosslinked with human placental extracellular matrix (hpcECM) to produce silk-gelatin-ECM composite hydrogels (SGE) with tunable mechanical properties, preserved elasticity, and bioactive functions. The SGE composite hydrogels were characterized in terms of gelation kinetics, protein folding, and bioactivity. The cyto- and biocompatibility of the SGE composite was determined by in vitro cell culture and subcutaneous implantation in a rat model, respectively. The most cell-supportive SGE formulation was then used for 3-dimensional (3D) bioprinting that induced chemical crosslinking during extrusion.ConclusionAddition of G-TA improved the mechanical properties of the SGE composite hydrogels and inhibited crystallization and subsequent stiffening of SF for up to one month. SGE hydrogels exhibit improved and tunable biomechanical properties and high bioactivity for encapsulated cells. In addition, its use as a bioink for 3D bioprinting with free reversible embedding of suspended hydrogels (FRESH) has been validated, opening the possibility to fabricate highly complex scaffolds for artificial soft tissue constructs with natural biomechanics in future.Graphical

Photopolymerized silk fibroin gel for advanced burn wound care

The future of burn wound treatment lies in developing bioactive dressings for faster and more effective healing and regeneration. Silk fibroin (SF) hydrogels have proven regenerative abilities and are being explored as a burn wound dressing. However, unfavorable gelation conditions limit the processability and clinical application. Herein a white light-responsive photopolymerization technique was adapted for gelation via photooxidation of tyrosine. To render the gel suitable for application to irregular and non-planar burn surfaces, SF gel-incorporated dressing (SFD) was fabricated. The mild gelation conditions using white light afforded the loading of drugs for local delivery. The moisture balance ability of the dressing was confirmed by the favorable measures of swelling capacity (106 ± 1 %) and moisture retention (≈10 h). The in vitro cytocompatibility of the gel was confirmed using HaCaT cells. Finally, in vivo performance of the SFD was tested on a second-degree burn in a rodent model. The gross analysis and histological assessment revealed scarless healing in SFD-treated groups. Overall, the SFD developed in this work is shown to be a promising candidate for advanced burn wound care.