A bioactive multi-functional heparin-grafted aligned poly(lactide-co-glycolide)/curcumin nanofiber membrane to accelerate diabetic wound healing

Highlights: • Aligned PC nanofibers were grafted with high density heparin to prepare PCH nanofiber membranes. • PCH improves curcumin release to induce higher cell migration and oxidative stress protection of skin fibroblasts. • PCH accelerates wound closure in diabetic rats by promoting re-epithelization, angiogenesis and collagen deposition. • PCH promote wound closure by sequestering endogenous growth factors TGF-β1 and FGF-2 in wound site. • Down regulation of GPx and NFκB expression by PCH relieves oxidative stress and inflammation to improve diabetic wound healing. Curcumin is reported to possess excellent efficacy to treat wounds that exhibit impaired healing. Heparin shows high affinity for many growth factors that are key biological mediators during the wound healing process. In this study, we aimed to prepare wound dressing membranes, for sustained release of an exogenous factor curcumin as well as sequestering endogenous growth factors at the wound site, to promote wound healing in diabetic rats. Toward this end, we prepared aligned curcumin-loaded poly(lactide-co-glycolide) (PLGA) nanofiber membranes (PC NFMs), followed by high density surface grafting of heparin to fabricate PLGA/curcumin (PCH) NFMs. Both PC and PCH NFMs show high tensile strength, low cytotoxicity and suitable water vapor transmission rate for application as wound dressings. Nonetheless, the PCH NFM shows higher curcumin release rate than PC due to enhanced hydrophilicity, which leads to higher cell migration rate and induced oxidative stress protection of HS68 fibroblast cells in vitro. In vivo study indicated the PCH exhibits the fastest wound closure rate among all membranes with accelerated re-epithelization rate, higher angiogenesis rate and more collagen deposition at the wound site. The accelerated and better skin tissue regeneration could be suggested to correlate with the multi-functionality of nanofibers, where grafted heparin attracting and stabilizing the growth factors important for wound healing in situ, together with relieving the high oxidative stress and the inflammatory cascade from released curcumin during diabetic wound healing.