Abstract

Diabetic chronic wounds, characterized by a dysregulated “infection-inflammation-angiogenesis” microenvironment, remain a pressing global health challenge. Single-functional therapies struggle to address this multi-factorial barrier, underscoring the need for innovative approaches. Herein, we engineered a pH-responsive coordination polymer (Cu-Cur CPs), formed by self-assembling curcumin (Cur) with Cu 2+ ions via coordination bonds, and encapsulated it within an electrospun PCL/sericin composite nanofiber membrane (CCSP). Cu-Cur CPs dissociate under acidic conditions (pH <6.5) to co-release Cur (anti-inflammatory/antioxidant) and Cu 2+ (antibacterial/pro-angiogenic), remaining stable at neutral pH (>7.0) to minimize off-target release. The PCL/sericin scaffold provides mechanical stability, biocompatibility, and a porous structure facilitating gas/nutrient exchange. In vitro , CCSP demonstrated pH-responsive release behavior, with 65.42% of Cur released under acidic conditions (pH 5.0) versus only 12.36% at neutral pH (7.4, p  < 0.05). Flow cytometric analysis further revealed that CCSP significantly modulated the immune microenvironment by upregulating CD206 (1.99-fold) and downregulating iNOS (1.97-fold) compared to SP controls. In a diabetic rat model with S. aureus -infected wounds, CCSP treatment significantly accelerated wound closure and improved healing quality—immunofluorescent analysis confirmed higher densities of α-SMA + and CD31 + . Collectively, this study provides a novel “carrier skeleton (PCL/sericin)-responsive release (Cu-Cur CPs)-multi-target synergy” paradigm for diabetic wound healing, offering a versatile platform for chronic wounds and multifactorial inflammation.