Body temperature-responsive Janus patches accelerate diabetic wound regeneration via coupling mechanical transduction and biochemical pathways.

Diabetic wound healing is impaired by the loss of mechanical tension at wound edges, a key driver of cellular proliferation and migration. This process remains unaddressed by conventional biochemical-focused therapies. Therefore, a shape memory adhesive regenerative therapeutic (SMART) patch was engineered for autonomous mechanical contraction and sustained bioactive ion release. The SMART patch consists of a shape memory polymer layer (LA-CA@Fe SMP) and an adhesive layer (LA-Zn Adhesive). The LA-CA@Fe SMP exhibited high shape recovery rate triggered at body temperature. The LA-Zn Adhesive offered robust wet adhesion with an interfacial shear strength of 22.30 kPa and controlled Zn2+ delivery. The patch demonstrated antibacterial efficacy and promoted fibroblast proliferation. In diabetic mice, the SMART patch achieved wound traction and promoted collagen deposition that accelerated wound closure by 50% and facilitated true skin regeneration with hair follicles and sebaceous glands. Furthermore, the SMART patch reshaped the wound microenvironment by enhancing M2 macrophage polarization and reducing oxidative stress. Transcriptomic analysis and verification of the protein expression levels indicated upregulation of yes-associated protein (YAP) and nuclear factor erythroid 2-related factor 2 (Nfr2) pathways involved in extracellular matrix remodeling, immune modulation, and cellular proliferation. This study introduces a combined mechano-chemical delivery system that addresses key limitations in diabetic wound healing, offering a promising controlled-release platform for regenerative therapy.