Accelerated diabetic wound healing via microenvironmental modulation treated by hydrogel encapsulated with neural stem cells

Diabetic wound healing is a highly coordinated, multi-stage process that relies critically on the pro-regenerative microenvironment. Recently, stem cell-based therapies have emerged as a promising paradigm in regenerative medicine, largely attributable to their inherent self-renewal capacity, multilineage differentiation potential, and pro-repair secretome. Despite these advances, the therapeutic potential of neural stem cells (NSCs) in cutaneous wound repair remains largely unexplored. We systematically evaluated the pro-angiogenic, antioxidant, and mitochondrial modulatory effects of NSCs on endothelial cells. A bio-inspired hydrogel was designed for NSC encapsulation with favorable preliminary biocompatibility. The in vivo pro-healing efficacy of NSCs-armed hydrogel was then assessed in diabetic mice. NSCs enhanced angiogenesis, antioxidant capacity, and mitochondrial function in endothelial cells. The engineered hydrogel exhibited favorable preliminary biocompatibility for the encapsulation of NSCs. This platform accelerated diabetic wound healing by regulating inflammation, promoting angiogenic, and exerting neural-supportive effects. This NSC-loaded hydrogel platform offers a promising and clinically relevant strategy for diabetic wound repair.