Abstract
Background: Airway epithelial injury is common in respiratory diseases and post-surgical conditions, leading to impaired barrier function and delayed healing. There remains an urgent need for localized biomaterial-based therapies to support epithelial repair under oxidative stress. Methods: We developed a self-healing injectable hydrogel based on chitosan and oxidized dextran, crosslinked via dynamic imine bonds. N-acetylcysteine (NAC) was encapsulated as a therapeutic payload. The hydrogel was characterized for rheological recovery, drug release kinetics, and evaluated in vitro using airway epithelial cells. Results: The hydrogel exhibited excellent self-healing behavior and sustained NAC release over 48 h. It promoted cell proliferation, enhanced migration in scratch assays, and upregulated ZO-1 expression. In an H₂O₂-induced injury model, NAC-loaded hydrogels significantly restored cell viability to near-normal levels. Conclusion: This NAC-loaded self-healing hydrogel provides both mechanical and biochemical support for airway epithelial repair. It offers a minimally invasive platform for localized treatment of airway injuries, with potential applications in respiratory disease management and post-operative mucosal healing.
Keywords: Self-healing hydrogel， airway epithelial repair， chitosan， oxidized dextran， N-acetylcysteine， dynamic covalent crosslinking， drug delivery