A Nanozyme-Loaded pH/Reactive Oxygen Species-Responsive Injectable Hyaluronic Acid/Gelatin Conductive Hydrogel for Coordinated Anti-Inflammation and Angiogenesis in Wound Healing

Complex wounds remain a clinical challenge due to their multifaceted pathophysiology, which involves persistent inflammation, oxidative stress, tissue hypoxia, and impaired angiogenesis. To address these issues, we developed an injectable, self-healing, and conductive hydrogel based on a dual dynamic covalent network formed by cross-linking phenylboronic acid-modified oxidized hyaluronic acid (OHA-PBA) and dopamine-grafted gelatin (GelDA). This network mimics the native extracellular matrix with its capacity for hydration regulation and cell adhesion, in addition to responding to the acidic and highly reactive oxygen species (ROS) wound microenvironment to enable intelligent drug release. By incorporating honeycomb-like manganese dioxide nanozymes (PHMP NPs) preloaded with puerarin (PUE) and conductive black phosphorus nanosheets (BP Ns), the hydrogel achieves sustained oxygen generation, ROS and reactive nitrogen species scavenging, electrical conductivity, and pro-angiogenic activity. In vivo experiments confirmed that the hydrogel significantly accelerates wound closure through multitarget mechanisms: downregulating pro-inflammatory factors (TNF-α, IL-6), promoting M2 macrophage polarization, and enhancing VEGF-mediated vascularization. This integrated strategy provides a comprehensive and translatable solution for advanced wound management.