ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

Treating diabetic wounds poses significant challenges due to the complex wound microenvironment, including bacterial infection, oxidative stress, inflammation, and impaired angiogenesis. We developed a novel curcumin nanoparticle formulation (ZnCur NPs) with excellent water dispersibility and stability, showcasing strong antibacterial, antioxidant, and anti-inflammatory properties. By encapsulating these ZnCur NPs along with RL-QN15 short peptides (with the function of promoting tissue repair and angiogenesis) into a hydrogel (CSA-OHAMA hydrogel, CO) based on chitosan and hyaluronic acid, we created a multifunctional hydrogel platform (Z/P/CO) that integrates antibacterial and immune-modulating functions. The Z/P/CO hydrogels are self-healing and adhesive, adapting to wound shapes while providing a protective barrier that minimizes bacterial invasion and maintains a moist environment. They effectively deliver ZnCur NPs and RL-QN15 peptides, enhancing antibacterial action and reshaping the adverse wound microenvironment. In vitro and in vivo results demonstrated that Z/P/CO significantly reduced inflammation, promoted angiogenesis, and facilitated collagen deposition, accelerating the healing of infected diabetic wounds within 17 days. This integrated hydrogel platform offers a promising strategy and effective method for treating diabetic wounds by reshaping the immune microenvironment.