Functionalized hydrogels of CeO2 and Urolithin A synergistically scavenge ROS and activate mitophagy for cartilage repair

In recent years, CeO₂ nanoparticles are promising biomaterials due to their excellent biocompatibility and antioxidant properties. This study utilizes a methacrylated gelatin (GelMA) hydrogel platform to construct a dual-functional composite material, CeUA@GelMA, by co-loading CeO₂ nanoparticles with urolithin A (UA). This material possesses both reactive oxygen species (ROS) scavenging and mitophagy activation capabilities, aiming to overcome the bottleneck in cartilage regeneration by regulating mitochondrial homeostasis. <i>In vitro</i> experiments confirmed that this material significantly reduces ROS levels within BMSCs under oxidative stress, maintains mitochondrial membrane potential, and promotes chondrogenic differentiation by upregulating genes such as Sox9, Col II, and ACAN. <i>In vivo</i> studies demonstrated that the CeUA@GelMA group achieved hyaline-like cartilage regeneration 8 weeks post-operation. The surface roughness of the newly formed cartilage was comparable to that of natural cartilage, with collagen and glycosaminoglycan density approaching normal cartilage levels. In summary, this research offers an innovative strategy and hydrogel material for cartilage tissue engineering through the regulation of mitochondrial homeostasis.