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Remodeling microenvironment based on MOFs-Hydrogel hybrid system for improving diabetic wound healing
Abstract Impaired healing of diabetic wounds is a critical threaten complication and still remains a vital clinical challenge, which are mainly characterized by the skin angiogenesis disorders and prolonged oxidative stress of the wound area. The specialty wound dressing systems with regular vascularization and reducing the inflammation are urgently desired. Herein, we present a remolding diabetic foot ulcer (DFU) microenvironment strategy that simultaneously reshaping wound microenvironment into a normal blood glucose and oxidative ones using a hybrid composites, which metformin hydrochloride (MH) and curcumin (Cur) incorporated in copper-based MOFs (HKUST-1), then Cur/MH/HKUST-1 impregnated into MH-loaded thermosensitive hydrogel (termed as Cur/MH/HKUST-1@Gel). The Cur/MH/HKUST-1@Gel was characterized by bio-stability, dual drug load efficiency and pH-dependent drug release patterns. The therapeutical efficiency of Cur/MH/HKUST-1@Gel in HaCat and HSF cells elucidated enhanced effects against oxidative stress, promotion the migration and growth of granulation tissue cells. The Cur/MH/HKUST-1@Gel retain sustained release of MH, Cur and Cu2+, also supply a moist microenvironment, and therefore significantly accelerate wound healing of diabetic mice. It was found that the Cur/MH/HKUST-1@Gel not only reformats the hostile DFU wound microenvironment, but also improves the wound closure as featured of newborn blood vessel, enhanced cell proliferation, highly deposition of collagen fiber, providing a promising candidate for the application of DFU healing.
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