Oxygenating Nanobubble Hydrogel for Accelerated Surgical Wound Closure and Restoration of Native Skin Architecture

Prolonged hypoxia and inflammation are critical barriers in postsurgical care, often leading to delayed healing and excessive scarring, which are complications that standard passive dressings fail to address. Here, we engineer a translationally focused oxygen-nanobubble-laden hydrogel (ONB-Gel) that actively orchestrates a phase-specific healing cascade. Composed of stable sodium alginate nanobubbles within a Carbopol matrix, the ONB-Gel provides a sustained oxygen source directly to the wound bed. In a clinically relevant rat surgical wound model, the application of ONB-Gel markedly outperformed the standard-of-care dressing (Adaptic), accelerating complete wound closure by over 25% and reducing the final scar width by more than 50%. Mechanistically, the ONB-Gel resolves tissue hypoxia, significantly downregulating inflammatory cytokines (IL-6, TNF-α), oxidative stress, and the chronic hypoxia marker. Critically, beyond accelerating closure, ONB-Gel promotes tissue regeneration, evidenced by dense, functionally aligned collagen deposition and the restoration of a near-normal epidermal architecture, unattainable with conventional dressings. Overall, ONB-Gel represents a promising platform for enhancing both the rate and the quality of postsurgical wound repair.