Mechano‐Activated Cell Therapy for Accelerated Diabetic Wound Healing

Abstract Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto‐responsive hydrogel, cells, and wireless magneto‐induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)‐approved fibroblasts and keratinocytes to achieve ∼3‐fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano‐rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto‐responsive property also enables on‐demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The “all‐in‐one” system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.