Hydrogel inspired by "adobe" with antibacterial and antioxidant properties for diabetic wound healing

With the aging population, the incidence of diabetes is increasing. Diabetes often leads to restricted neovascularization, antibiotic-resistant bacterial infections, reduced wound perfusion, and elevated reactive oxygen species, resulting in impaired microenvironments and prolonged wound healing. Hydrogels are important tissue engineering materials for wound healing, known for their high water content and good biocompatibility. However, most hydrogels suffer from poor mechanical properties and difficulty in achieving sustained drug release, hindering their clinical application. Inspired by the incorporation of fibers to enhance the mechanical properties of "adobe," core-shell fibers were introduced into the hydrogel. This not only improves the mechanical strength of the hydrogel but also enables the possibility of sustained drug release. In this study, we first prepared core-shell fibers with PLGA (poly(lactic-co-glycolic acid)) and PCL (polycaprolactone). PLGA was loaded with P2 (Parathyroid hormone-related peptides-2), developed by our group, which promotes angiogenesis and cell proliferation. We then designed a QTG (QCS/TA/Gel, quaternary ammonium chitosan/tannic acid/gelatin) hydrogel, incorporating the core-shell fibers and the anti-inflammatory drug celecoxib into the QTG hydrogel. This hydrogel exhibits excellent antibacterial properties and biocompatibility, along with good mechanical performance. This hydrogel demonstrates excellent water absorption and swelling capabilities. In the early stages of wound healing, the hydrogel can absorb the wound exudate, maintaining the stability of the wound micro- environment. This hydrogel promotes neovascularization and collagen deposition, accelerating the healing of diabetic wounds, with a healing rate exceeding 95 % by day 14. Overall, this study provides a promising strategy for developing tissue engineering scaffolds for diabetic wound healing.