Evaluation of natural protein-based nanofiber composite photocrosslinking hydrogel for skin wound regeneration.

Protein based photocrosslinking hydrogels with nanofiber dispersions were reported to be an effective wound dressing. In this study, two kinds of protein (gelatin and decellularized dermal matrix) were modified to obtain GelMA and ddECMMA, respectively. Poly(ε-caprolactone) nanofiber dispersions (PCLPBA) and thioglycolic acid-modified chitosan (TCS) were added into GelMA solution and ddECMMA solution, respectively. After photocrosslinking, four kinds of hydrogel (GelMA, GTP4, DP and DTP4) were fabricated. The hydrogels showed excellent physico-chemical property, biocompatibility and negligible cytotoxicity. When applied on the full-thickness cutaneous deficiency of SD rats, hydrogel treated groups exhibited an enhanced wound healing effect than Blank group. Besides, the histological staining of H&E and Masson's showed that hydrogels groups with PCLPBA and TCS (GTP4 and DTP4) improved wound healing. Furthermore, GTP4 group performed better healing effect than other groups, which had great potential in skin wound regeneration.

A photocrosslinking antibacterial decellularized matrix hydrogel with nanofiber for cutaneous wound healing.

ddECMMA is the methacrylating product of decellularized dermal extracellular matrix with biological signals and capable of photocrosslinking. Thiolated chitosan (TCS) is an effective antibacterial component. PCLPBA is a kind of plasma-treated polycaprolactone nanofiber dispersions (PCLP) that regulates macrophage polarization and promotes angiogenesis. In this study, we obtained ddECMMA via methacrylation reaction. TCS was prepared by reaction between chitosan and thioglycolic acid. PCLPBA was fabricated via reaction between PCLP and 3-buten-1-amine. TCS and PCLPBA were mixed in ddECMMA solution and photocrosslinked to form DTP4 hydrogel. The hydrogel showed rapid gelation, good mechanical strength, antibacterial and antioxidant properties. When it was cocultured with NIH 3T3 cells, the cells showed good morphology and proliferation rate. After applying it to the full-thickness cutaneous wound, wounds almost healed in 2 weeks via re-epithelialization and neovascularization with negligible scar tissue. The results indicate that DTP4 hydrogel is a promising candidate for clinic skin wound healing.

Injectable hyaluronic acid hydrogel encapsulated with Si-based NiO nanoflower by visible light cross-linking: Its antibacterial applications.

Bacterial infections have become a severe threat to human health and antibiotics have been developed to treat them. However, extensive use of antibiotics has led to multidrug-resistant bacteria and reduction of their therapeutic effects. An efficient solution may be localized application of antibiotics using a drug delivery system. For clinical application, they need to be biodegradable and should offer a prolonged antibacterial effect. In this study, a new injectable and visible-light-crosslinked hyaluronic acid (HA) hydrogel loaded with silicon (Si)-based nickel oxide (NiO) nanoflowers (Si@NiO) as an antibacterial scaffold was developed. Si@NiO nanoflowers were synthesized using chemical bath deposition before encapsulating them in the HA hydrogel under a mild visible-light-crosslinking conditions to generate a Si@NiO-hydrogel. Si@NiO synthesis was confirmed using scanning electron microscopy, transmission electron microscopy, and powder X-ray diffraction. As-prepared Si@NiO-hydrogel exhibited enhanced mechanical properties compared to a control bare hydrogel sample. Moreover, Si@NiO-hydrogel exhibits excellent antibacterial properties against three bacterial strains (P. aeruginosa, K. pneumoniae, and methicillin-resistant Staphylococcus aureus (>99.9% bactericidal rate)) and negligible cytotoxicity toward mouse embryonic fibroblasts. Therefore, Si@NiO-hydrogel has the potential for use in tissue engineering and biomedical applications owing to its injectability, visible-light crosslink ability, degradability, biosafety, and superior antibacterial property.

Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect.

There is no therapy currently available for fully repairing articular cartilage lesions. Our laboratory has recently developed a visible light-activatable methacrylated gelatin (mGL) hydrogel, with the potential for cartilage regeneration. In this study, we further optimized mGL scaffolds by supplementing methacrylated hyaluronic acid (mHA), which has been shown to stimulate chondrogenesis via activation of critical cellular signalling pathways. We hypothesized that the introduction of an optimal ratio of mHA would enhance the biological properties of mGL scaffolds and augment chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). To test this hypothesis, hybrid scaffolds consisting of mGL and mHA at different weight ratios were fabricated with hBMSCs encapsulated at 20 × 106  cells/ml and maintained in a chondrogenesis-promoting medium. The chondrogenenic differentiation of hBMSCs, within different scaffolds, was estimated after 8 weeks of culture. Our results showed that mGL/mHA at a 9:1 (%, w/v) ratio resulted in the lowest hBMSC hypertrophy and highest glycosaminoglycan production, with a slightly increased volume of the entire construct. The applicability of this optimally designed mGL/mHA hybrid scaffold for cartilage repair was then examined in vivo. A full-thickness cylindrical osteochondral defect was surgically created in the rabbit femoral condyle, and a three-dimensional cell-biomaterial construct was fabricated by in situ photocrosslinking to fully fill the lesion site. The results showed that implantation of the mGL/mHA (9:1) construct resulted in both cartilage and subchondral bone regeneration after 12 weeks, supporting its use as a promising scaffold for repair and resurfacing of articular cartilage defects, in the clinical setting.