Microalgae extracellular vesicles-loaded dual antioxidative and anti-inflammatory hydrogel system for wound healing and peripheral nerve repair in diabetes

, mEVs@TAgel significantly reduced ROS levels by activating the Nrf2 signaling pathway, enhanced mitochondrial function in keratinocytes and Schwann cells, and drove M1-to-M2 macrophage polarization via suppression of NF-κB signaling. In diabetic mice, treatment with mEVs@TAgel accelerated full-thickness wound closure, promoted re-epithelialization, angiogenesis, and collagen remodeling, and reduced scar formation through early Col 3 deposition and an improved Col 3/Col 1 ratio. Notably, in a sciatic nerve injury model, mEVs@TAgel enhanced functional recovery, axonal regeneration, remyelination, and muscle preservation. Long-term biosafety evaluations showed no systemic toxicity or inflammatory side effects. Altogether, mEVs@TAgel represents a safe and potent platform that coordinately mitigates oxidative stress, inflammation, and tissue damage, offering a promising strategy for diabetic wound and nerve repair.