Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy

Osteoarthritis (OA), characterized by chronic inflammation and cartilage degeneration, significantly affects over 500 million people globally. Nanoparticles have emerged as promising treatments for OA; however, current strategies often employ a single type of nanoparticle targeting specific disease stages, limiting sustained therapeutic efficacy. In this study, a novel collagen hydrogel is introduced, thiol crosslinked collagen-cerium oxide-poly(D,L-lactic-co-glycolic acid) microspheres encapsulating nanoparticles (CSH-CeO₂-pFe₂O₃), designed for the controlled release of cerium oxide (CeO₂) and ferric oxide (Fe₂O₃) nanoparticles for comprehensive OA management. The sulfhydryl cross-linked collagen matrix embeds CeO₂ nanoparticles and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating Fe₂O₃ nanoparticles. The CSH-CeO₂-pFe₂O₃ hydrogel exhibits enhanced mechanical strength and remarkable injectability, along with a significant promotion of cell adhesion, proliferation, and chondrogenic differentiation. Notably, the hydrogel demonstrates intelligent responsiveness to high levels of reactive oxygen species, initiating the rapid release of CeO₂ nanoparticles to address the intense inflammatory responses of early-stage OA, followed by the sustained release of Fe₂O₃ nanoparticles to facilitate cartilage regeneration during the proliferative phase. In a rat model with cartilage defects, the hydrogel significantly alleviates inflammation and enhances cartilage regeneration, holding substantial potential for effectively managing the pathologically complex OA.