Hai Zhou, Chaoyang Huang, Yanqi Chen, Tingzi Zhao, Fengyi Zhu, Gong Jun, Jinrong Zhang, Yingsong Pan, Qiulan Wen, Lei Yang, Huihui Zhang, Lianglong Chen
ABSTRACT Diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, and susceptibility to infection, posing significant clinical challenges. Here, we report an intelligent shape‐memory sponge (P 1 A 3 @B‐MOF) engineered for the programmable modulation of the diabetic wound microenvironment. The dressing consists of an interpenetrating network of oxidized pullulan and acellular dermal matrix, incorporating zeolitic imidazolate framework‐8 (ZIF‐8) metal–organic frameworks encapsulated with salvianolic acid B (SalB) via in situ self‐assembly. This design enables exudate‐triggered shape recovery and pH‐responsive drug release, targeting the acidic pathological environment. We demonstrate that the released Zn 2+ and SalB exert synergistic effects: conferring broad‐spectrum antibacterial activity, orchestrating macrophage repolarization from proinflammatory M1 to regenerative M2 phenotypes, and activating the hypoxia‐inducible factor 1‐alpha (Hif‐1α)/vascular endothelial growth factor (VEGF) pathway to restore vascularization. In a diabetic rat model, the sponge accelerated wound closure with a 98.5% healing rate by day 14 and modulated collagen deposition via the transforming growth factor‐β (TGF‐β)/Smad signaling axis, thereby effectively mitigating scar formation. This integrated strategy offers a promising modality for restoring immune homeostasis and promoting functional skin regeneration.