Injectable silk fibroin methacrylate hydrogels with coordination-coupled cerium-polyphenol nanoassemblies for...

Cartilage repair is hindered by an injury-driven microenvironment characterized by oxidative stress and persistent inflammation, while conventional structural hydrogels largely function as passive matrices. Here we develop an injectable, in situ photocurable, and cell-free hydrogel by integrating cerium-tea polyphenol nanoassemblies (CeTP) with a silk fibroin methacrylate (SilMA) network, establishing a colloid-network coupled platform termed CeTP-SilMA. Spectroscopic and surface-chemical analyses substantiate the metal-phenolic coordination underlying CeTP formation and its interfacial coupling with the polymer network. This coupling yields rapid on-demand gelation, reinforced network integrity, and concentration-dependent radical-scavenging activity, together with prolonged local antioxidative potential associated with cerium redox activity and tea polyphenol-mediated regulation. Functionally, CeTP-SilMA suppresses nuclear factor kappa B (NF-κB)-associated inflammatory activation, reduces pro-inflammatory outputs, and biases macrophages toward a pro-regenerative phenotype, thereby linking immune modulation with redox homeostasis. Under oxidative stress, CeTP-SilMA preserves chondrocyte mitochondrial function, improves viability, and promotes chondrogenic differentiation and matrix formation. In a rat osteochondral defect model, injectable photocuring delivery supports cartilage-like matrix deposition and improved osteochondral structural repair compared with structural controls. Overall, this work highlights a coordination-enabled route to engineer redox-active and immunomodulatory hydrogel interfaces via colloid-network integration for cartilage regeneration.