Gelatin-oxidized dextran Schiff base hydrogel with MXene@TiO₂ and GHK-Cu: A multifunctional dressing for photothermal-antibacterial and pro-angiogenic wound repair

Chronic wound healing is often impaired by persistent pathogenic infection, excessive oxidative stress, and insufficient angiogenic drive. In this study, a multifunctional injectable hydrogel dressing (Gel/ODex/MT/GHK-Cu) was developed based on a dynamic chemical network to accelerate skin tissue regeneration through the synergistic effects of photothermal antibacterial therapy and biochemical signaling. The system utilizes dynamic Schiff base crosslinking between gelatin (Gel) and oxidized dextran (ODex) as the structural framework, integrating MXene@TiO 2 (MT) heterojunction nanosheets and copper peptide (GHK-Cu) as functional units. Results demonstrated that the hydrogel possessed excellent rheological properties, self-healing capacity, and tissue adhesiveness (with adhesion strength sufficient to withstand various skin movements), with a swelling ratio exceeding 200% for effective exudate management. Under 808 nm near-infrared (NIR) irradiation, the MT heterojunction nanosheets exhibited significant photothermal conversion capability, raising the local temperature above 45 °C within 15 min, achieving efficient ablation (>99%) of Staphylococcus aureus and Escherichia coli through the synergy of hyperthermia and the physical-mechanical disruption of bacterial membranes. Meanwhile, the sustained release of Cu 2 + from GHK-Cu provided outstanding antioxidant activity and significantly enhanced the migration of human umbilical vein endothelial cells. In vivo evaluations in a mouse full-thickness skin defect model confirmed that the hydrogel combined with NIR treatment significantly shortened wound closure time and promoted re-epithelialization, collagen deposition, and the formation of functional hair follicles. By establishing an integrated platform for physical protection, precise ablation, and bio-inspired repair, this study offers a promising advanced strategy for the clinical management of chronic infected wounds. Download: Download high-res image (126KB) Download: Download full-size image A multifunctional injectable hydrogel dressing was developed via Schiff base crosslinking of gelatin and oxidized dextran, incorporating MXene@TiO₂ nanosheets and GHK‑Cu. The hydrogel shows excellent photothermal antibacterial activity, anti-inflammatory effect, and sustained Cu²⁺ release to promote angiogenesis and L929 cell proliferation. Combined with NIR irradiation, the hydrogel significantly accelerates full‑thickness wound healing in mice by enhancing re‑epithelialization, angiogenesis, collagen deposition, and hair follicle regeneration.