Injectable Thermosensitive Thiol-Modified NIPAAm-g-Chitosan Hydrogels for Cartilage Regeneration in a Rabbit Osteoarthritis Model

Abstract

Cartilage tissue has a limited intrinsic capacity for self-healing. Over the decades, researchers have extensively researched methods of cartilage repair, yet some limitations still need to be resolved. Most studies typically evaluate osteochondral regeneration in normal animals. However, traumatic articular cartilage defects may eventually result in osteoarthritis (OA), and the relationship between cartilage defects and OA is not independent. Therefore, in this study, the effect of thiol-modified NIPAAm-g-chitosan (TNC) hydrogels containing human adipose-derived mesenchymal stem cells (hADMSCs), with or without etanercept, a TNF-α inhibitor, was evaluated for cartilage regeneration in a monosodium iodoacetate (MIA)-induced OA rabbit model. TNC hydrogels, with a suitable lower critical solution temperature (LCST), porous interior microstructures, enhanced mechanical properties, and without cytotoxicity were synthesized and characterized by DSC, SEM, NMR, and the CCK8 kit. The OA rabbit models were established by MIA injection in the rabbit knees and verified with histological examinations and cytokine detection for IL-1β, IL-6, and TNF-α. According to macroscopic evaluations, micro-CT analysis, and histological and immunohistochemical evaluations, the results of cartilage repair in OA models showed improvement in cartilage regeneration in the cell-seeded hydrogel groups compared with the empty defect groups. Furthermore, etanercept effectively promoted osteochondral defect repair in the first 4 weeks. In OA models, TNC hydrogels containing hADMSCs and etanercepts could be promising for cartilage tissue engineering.