CaO2 nanoparticle-loaded injectable hydrogel with sustained oxygen release and ROS-scavenging functions for accelerating frostbite wound healing at high altitude

Abstract

Frostbite is common in high-altitude regions, where low oxygen levels and the cold climate aggravate wound hypoxia and reactive oxygen species (ROS) accumulation, making frostbite lesions prone to becoming hard-to-heal wounds. Traditional hydrogel dressings remain unsatisfactory under such extreme conditions, as they lack freezing resistance, low-temperature adhesion, sustained oxygen release, and ROS-scavenging activity. Herein, we report a multifunctional hydrogel for the management of high-altitude frostbite wounds, formed from polyvinylpyrrolidone-coated CaO₂ nanoparticles (CPO NPs), polyvinyl alcohol, tannic acid (TA), and glycerol through dynamic hydrogen-bonding interactions. The resulting CPO-PTG hydrogel exhibits injectability, rapid gelation, shape adaptability and self-healing, enabling conformal coverage of irregular frostbite wounds. The inclusion of glycerol endows the hydrogel with excellent antifreezing and water-retention properties, while reinforcing multiple covalent and noncovalent interactions between TA within the hydrogel and wound tissues, resulting in strong adhesion even at −20 °C. TA also contributes strong antibacterial activity, helping prevent wound infection. Notably, the hydrogel network regulates oxygen release from CPO NPs to achieve sustained oxygen delivery for 12 days and, together with the ROS-scavenging activity of TA, promotes cell proliferation and tube formation in vitro under hypoxic conditions. In a rat frostbite-induced hypoxic wound model, CPO-PTG hydrogel accelerates wound healing by reducing inflammation and enhancing angiogenesis. Therefore, this multifunctional hydrogel offers a promising strategy for frostbite wound repair, with potential applicability to other hypoxic wounds in high-altitude settings.