Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe₂O₃ nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe₂O₃ providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe³⁺. In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.