A rationally engineered PVA-HA hydrogel orchestrates osteochondral regeneration and matrix mineralization by cytoprotecting chondrocytes mitochondrion

Functional hydrogels based on carbohydrates are continually gaining research attention owing to their biological suitability and rationally engineered functions. Injectable hydrogels developed based hyaluronic acid (HA) and polyvinyl alcohol (PVA) have been reported to be attracting for osteoarthritis (OA) treatment. However, the excessive reactive oxygen species (ROS) in the oxidative stress microenvironment instigate chondrocyte mitochondrial damage and worsen cartilage degeneration, while conventional hydrogels cannot modulate oxidative stress. Consequently, this study proposed a strategy to rational design of dual-network PVA-HA hydrogels enables spatiotemporal control over anti-inflammatory cytokine release and ROS-scavenging functions, providing a disease-modifying therapeutic platform for OA through synergistic biomaterial-mediated microenvironment regulation. The designed hydrogels (PB-CaP@H) were enhanced by mineralized nanozymes (2 nm calcium phosphate (CaP) clusters modified Prussian blue (PB)), forming a composite hydrogel system that synergistically integrates near-infrared (NIR) response, anti-oxidative stress, and pro-cartilage mineralization functions. PB-CaP@H hydrogel has a porous structure (61 % porosity) and excellent mechanical properties (169 % elongation). Upon NIR irradiation, it warms the joint cavity to 48.9 °C, enhancing ROS scavenging (81 %) and accelerating mitochondrial repair. Micro-CT shows reduced cartilage damage. Molecular experiments confirm it repairs cartilage by up-regulating Col-II and SOX9. This injectable hydrogel offers a new OA treatment strategy by combining anti-oxidative stress therapy with cartilage repair.