Functionally modular hydrogel enables dynamic sensing and adaptive regulation for wound regeneration

Impaired wound healing, typified by diabetic ulcers, is driven by sustained inflammation, compromised angiogenesis, and a susceptibility to infection, which collectively disrupt tissue repair and functional regeneration. To address this challenge, therapeutic systems capable of dynamically sensing and actively modulating the wound milieu are urgently needed. Here, we present a functionally compartmentalized theranostic hydrogel platform that integrates real‑time infection monitoring with coordinated immunomodulatory and pro-angiogenic regulation. The system comprises a sensing base layer with high-sensitivity resistive temperature response via ion-doping, enabling real-time detection of local temperature elevation associated with infection, and a therapeutic layer containing engineered microspheres loaded with anti-inflammatory diclofenac sodium and vascular endothelial growth factor (VEGF), enabling temperature-triggered anti-inflammatory modulation alongside sustained pro-angiogenic support. In a diabetic full-thickness wound model, the hydrogel platform demonstrated real‑time monitoring capability and multifunctional therapeutic activity: it effectively suppressed excessive inflammation, enhanced vascular network formation, accelerated wound closure by approximately 80%, improved collagen organization, and promoted functional skin regeneration. By integrating dynamic sensing with on‑demand drug release, this sense-and-respond strategy offers a modular and adaptive platform for precision management of chronic, hard‑to‑heal wounds. The functionally compartmentalized theranostic hydrogel platform enables real-time monitoring of diabetic wounds while promoting tissue regeneration through inflammation regulation, macrophage polarization, and enhanced angiogenesis.