A Magnesium-Phenolic Coordinated Hydrogel Orchestrates Antiapoptotic, Immunomodulatory, and Angiogenic Niches for Aging Wound Regeneration

Geriatric cutaneous wound healing is impeded by a senescent microenvironment characterized by excessive oxidative stress, persistent inflammation, and impaired vascularization. While conventional therapies are often constrained by suboptimal efficacy in aged skin, emerging biomaterial-based strategies offer promising avenues for microenvironment reprogramming. Based on transcriptomic profiling revealing specific deficits in Nrf2-mediated antioxidant defense and VEGF signaling in senescent wounds, we report a magnesium-phenolic coordinated hydrogel, designated as the Aging-resistant Ionogel Dressing (AID), which is engineered by assembling bioactive magnesium ions (Mg2+) and polydopamine (PDA) within a polyvinyl alcohol (PVA) network. This design leverages metal-phenolic coordination chemistry to target vascular insufficiency, redox imbalance, and immune dysregulation. Physically, the dynamic coordination bonds endow the hydrogel with optimized viscoelasticity and robust tissue adhesiveness. Biologically, AID acts as a potent reactive oxygen species (ROS) scavenger to inhibit oxidative apoptosis, while exhibiting intrinsic antibacterial activity. Furthermore, AID remodels the immune niche by driving macrophage transition from pro-inflammatory (M1) to pro-regenerative (M2) phenotypes, while sustained Mg2+ release drives robust angiogenesis. In aged ICR mice, AID significantly accelerates wound closure, potentiates collagen deposition, and restores functional vascular networks. This study presents a comprehensive strategy to revitalize the senescent microenvironment, offering a translational breakthrough for geriatric wound management.