Folic Acid- and Nanochitin-Based Hydrogel Matrix Incorporating CeO2/ZnO-Loaded Montmorillonite for Oxidative Stress-Modulated Wound Healing

Abstract The limited self-repair capacity of skin necessitates advanced wound dressings that can accelerate healing, prevent infection, and promote tissue regeneration. Herein, we constructed a supramolecular hydrogel via hydrogen bonding and electrostatic interactions among deacetylated nanochitin (TCN), folic acid (FA), and CeO2/ZnO-loaded montmorillonite (FA/CZM-TCN). TCN, in coordination with FA, constituted a biomimetic extracellular matrix scaffold that effectively promoted cell migration. When the hydrogel dressing is injected into irregular skin wounds in mice, it exhibits favorable wettability and conformal coverage of the wound bed immediately after injection. The wound closure rate reached 95% on day 12, demonstrating accelerated healing. Notably, the incorporation of CeO2/ZnO-loaded montmorillonite not only reinforced the mechanical performance and structural integrity of the hydrogel but also synergistically conferred sustained antibacterial and antioxidant capabilities, thereby effectively mitigating local oxidative stress. In a full-thickness wound model, the hydrogel significantly accelerated healing compared to untreated controls, as evidenced by faster closure rates, enhanced angiogenesis, and increased collagen deposition (Masson trichrome staining). We hypothesize that the antioxidant and antibacterial functions of CeO2/ZnO-loaded montmorillonite synergize with the TCN/FA scaffold to accelerate healing.