Isorhynchophylline-loaded silk sericin/gelatin methacrylate crosslinked hydrogel: A synergistic platform for...

Acute and chronic wounds face substantial clinical hurdles from pathological inflammation and poor tissue regeneration, with current therapies failing to integrate drug delivery and microenvironment modulation. We engineered an isorhynchophylline-loaded silk sericin/gelatin methacrylate (IRN@SS/GelMA) hydrogel via thermo-induced co-assembly at 37 °C. This hydrogel system is multifunctional. Structural characterizations (SEM, XRD, FTIR, and mechanical testing) reveal that the SS-GelMA matrix forms a macroporous structure. Compared with GelMA, it has 50 % higher porosity. Moreover, its thermal stability is enhanced, with a decomposition temperature that is 50 °C higher. The hydrogel also demonstrates biocompatibility and sustained drug release kinetics, achieving 73 % cumulative release over 6 days, along with dual - phase therapeutic efficacy. In murine wound models, it markedly accelerates wound closure. Mechanistically, it alleviates inflammation by reducing the levels of IFN-γ and CSF. It also promotes collagen deposition. Transcriptomic analysis validates the coordinated up - regulation of VEGF, FGF, and EGF pathways, coupled with the suppression of TNF and IL-17 signaling. By integrating the antioxidative and anti - inflammatory properties of SS, the structural support of GelMA, and the immunomodulatory capability of IRN, this platform enables scar-minimized wound healing through spatiotemporal regulation of the regeneration cascade. Overall, our work presents a promising regenerative strategy for wound repair, emphasizing immunomodulation and the regulation of the wound regeneration process.