Curcumin loaded hydrogel with anti-inflammatory activity to promote cartilage regeneration in immunocompetent animals

Stable cartilage regeneration in immunocompetent animals remains a huge challenge, mainly ascribing to the in vivo implantation of tissue-engineered cartilage inevitably arousing inflammatory reactions, resulting in cartilage-specific extracellular matrix erosion, chondrogenic niche destruction, and chondrocyte deterioration. Herein, we developed an anti-inflammatory platform, namely, Cur/GelMA hydrogel, by loading a potent anti-inflammatory drug of curcumin (Cur) into gelatin methacryloyl (GelMA) hydrogel. The Cur/GelMA hydrogel exhibited satisfactory Cur release kinetics in vitro and exerted favorable anti-inflammatory effects when cocultured with lipopolysaccharide-induced RAW264.7 macrophages in vitro. Furthermore, the Cur/GelMA hydrogel showed gratifying biocompatibility and supported cartilage regeneration in vitro when colonized with rabbit- and goatderived chondrocytes. In addition, the in vitro engineered cartilages in the Cur/GelMA hydrogel were able to maintain a cartilaginous phenotype and achieved stable cartilage regeneration when subcutaneously implanted in autologous rabbits and goats for 2 and 4 weeks compared to the GelMA hydrogel. Furthermore, our data revealed that the in vivo-generated cartilage in the Cur/GelMA group apparently alleviated the inflammatory reaction compared to its GelMA counterpart, suggesting that the locally released Cur endowed the Cur/GelMA hydrogel with potent anti-inflammatory capacity. This study provides a reliable anti-inflammatory platform for stable cartilage regeneration in immunocompetent animals, significantly advancing the clinical application of tissue-engineered cartilage.