Self-Evolving Hydrogel Dressing Temporally Accelerates Infected Diabetic Wound Healing.

Abstract

Diabetic wounds usually involve disorganized redox and immune homeostasis and are prone to bacterial infection, often leading to delayed healing and worse outcomes. However, existing therapeutic strategies cannot simultaneously achieve potent antibacterial action and temporal microenvironment modulation. Herein, a self-evolving hyaluronan/poly(aspartic acid) hydrogel dressing integrating in situ Ag⁺-to-Ag nanozyme conversion function and hydrolyzable Fe₃N/Fe₃O₄ nanoheterojunction (nHJ) is presented to meet the intricate requirements of consecutive healing stages. At infectious inflammatory stage, nHJ-based self-oxygenated photodynamic and photothermal effects synergize with Ag⁺ to combat multidrug-resistant biofilm-forming bacteria. Subsequently, Ag nanozymes with superoxide dismutase/catalase-like activities continuously scavenge reactive oxygen species while generating oxygen, facilitating macrophage M1-to-M2 repolarization and ensuing inflammatory-to-proliferative phase transition. Accumulated ammonia enhances cell proliferation, migration and angiogenesis. The dressing demonstrates exceptional biocompatibility and bioactivity in accelerating Staphylococcus aureus-infected full-thickness cutaneous wound healing in a diabetic rat model, as validated by hemostatic, broad-spectrum antibacterial, antioxidative and immunomodulatory abilities, enhanced oxygenation and cell proliferation, and extensive collagen deposition, vascularization and re-epithelialization. RNA-seq results further reveal the activation of multiple pro-healing signaling axes. Consequently, this platform offers a powerful dynamic strategy of realizing robust antibacterial activity and active temporal niche modulation to guide the healing of infected diabetic wounds.