Towards scarless repair: MMP-2 responsive drug releasing nanofibrous mat restores homeostasis via fibroblasts’ activation

Abstract

The failure of wound repair, particularly in cases of refractory wounds, is closely associated with immune disorders, leading to serious consequences such as scarring and ulcers. To address this issue, Poly [octanediol-co- (citric acid)] (POCA)/gelatin curcumin-loaded nanofibrous mats responsive to inflammatory microenvironments are developed. POCA serves as a cross-linker for gelatin, providing the nanofibrous mat with skin-like J-shaped stress-strain behavior. Moreover, the pendant carboxyl groups of POCA enable adhesion ability in the wet state, thereby increasing wound sealing. Most importantly, the as-prepared nanofibers are sensitive to MMP-2. Amorphous curcumin is responsively released in response to high MMP levels present in inflammatory wounds. This significantly enhances curcumin's efficiency. The mat exhibits substantial therapeutic effects on chronic diabetic wounds and tension-loaded wounds, nudging wound healing toward regenerative repair. Moreover, it was also shown to promote basement membrane renewal by activating wound fibroblasts, which mitigates the immune response and reinstate homeostasis.