Magnetically Programmable Hydrogel Enables Sequential Thermo-Mechano Therapy for Infected Diabetic Wound Healing

Wound healing in diabetic patients is severely compromised by persistent infection, impaired tissue integrity, and chronic inflammation. Here, a thermoresponsive magnetic hydrogel dressing (MHd; PNIPAm-PAm/Laponite/Fe₃O₄/TA) is developed to enable magnetically programmable, time-sequenced thermos-mechano-biochemical regulation for infected diabetic wounds. MHd integrates a temperature-sensitive polymer network, magnetic Fe₃O₄ nanoparticles, and the natural polyphenol tannic acid (TA), allowing external control under an alternating magnetic field (AMF). By temporally adjusting AMF intensity, MHd can be programmed to operate in distinct therapeutic modes across different treatment phases. High-intensity AMF induces rapid magnetothermal sterilization and thermoresponsive contraction, generating mechanical traction to accelerate early wound closure while triggering burst TA release for synergistic antibacterial and antioxidant effects. Subsequent low-intensity AMF maintains mild mechanical regulation and sustained TA release to support continuous bacterial suppression, reactive oxygen species scavenging, and tissue regeneration. In the absence of AMF, MHd remains in a resting mode with baseline TA release to stabilize the wound microenvironment. In vitro and in vivo studies demonstrate effective antibacterial activity, accelerated wound closure, enhanced angiogenesis, and collagen deposition. Mechanistic analyses suggest that mechanical regulation promotes healing via integrin-related mechanotransduction signaling. Overall, this work presents a magnetically programmable, stage-adaptive wound dressing for diabetic wound therapy.