Modulating Calcium Homeostasis via a Biomimetic Scaffold to Rescue Diabetic Ischemic Wounds

Abstract

ABSTRACT Diabetic wound healing is critically impaired by a pathological microenvironment with two core barriers: circulatory deficits from microangiopathy, and a loss of nanoscale topographical guidance due to extracellular matrix (ECM) disruption. To address this, we developed Musc@CP, an advanced dressing that synergistically combines an ECM‐mimetic multi‐property scaffold with active vascular modulation. The platform is based on a chitosan‐pullulan (CP) nanofibrous scaffold that structurally recapitulates healthy dermal ECM to direct fibroblast adhesion and migration. The matrix incorporates muscone (Musc), a bioactive compound that attenuates intracellular Ca2+ overload‐associated endothelial dysfunction and is associated with improved local perfusion. This restoration of blood circulation may contribute to reprogramming the immune microenvironment within the wound, helping to suppress both inflammation and oxidative stress. Consequently, the healing progression in diabetic mice is effectively restored. Together, this integrated strategy represents a promising and mechanistically sound therapy for chronic diabetic wounds.