Bioadhesive and hemostatic microneedles integrated with NIR-responsive TiC/CeOheterojunction nanozymes for accelerated diabetic wound healing.

Abstract

RATIONALE: The hyperglycemic microenvironment and microvascular dysfunction in diabetic wounds induce excessive reactive oxygen species (ROS) accumulation and persistent bleeding, severely impeding healing. Conventional nanozymes can scavenge ROS by mimicking the activities of superoxide dismutase (SOD) and catalase (CAT), but generally exhibit low catalytic efficiency and poor physiological stability. Fabricating nanozyme heterojunctions offers a viable approach to circumventing the aforementioned drawbacks. METHODS: TC (TiC/CeO) heterojunctions were fabricated via an etching step followed by a solvothermal approach. The TC nanosheets were incorporated into a GelMA hydrogel to form the tip layer, while methacrylated dopamine (DMA) was integrated into the base layer for bio-adhesive functionality. A bilayer microneedle patch (GTM) was fabricated via a two-step photopolymerization process. The hemostatic capacity, photothermal conversion, and antioxidation properties were systematically examined. Meanwhile, animal experiments were executed utilizing a rabbit model of hepatic bleeding and a severe cutaneous defect model in diabetic Sprague-Dawley (SD) rats. RESULTS: Under NIR irradiation, the TC heterojunction exhibited significantly enhanced antioxidant enzymatic activity, driven by synergistic interfacial charge transfer and photothermal effects. The bio-adhesive base layer achieved rapid hemostasis in a hepatic hemorrhage model, reducing blood loss from 6.51 g to 0.93 g. A highly accelerated wound healing process was observed in a diabetic rat model of full-thickness skin defects following treatment with GTM under NIR irradiation, achieving 99.89% wound closure by Day 20 while alleviating oxidative stress and promoting collagen deposition. CONCLUSION: This study developed a bifunctional wound repair platform by integrating a strongly adhesive microneedle base with NIR-responsive heterojunction nanozymes, providing novel insights for overcoming challenges in diabetic wound healing.