Lacuna-mimic human-derived nasal septal chondrocyte clusters encapsulated in click chemistry-based hydrogel for in vivo cartilage regeneration

In the lacuna structure of cartilage, a small group of chondrocytes are contacted and surrounded by extracellular matrix. To mimic this structure, we applied tannic acid (TA)-based clustering and click chemistry-based hydrogel to our human-derived nasal septal chondrocytes (hNCs) with advantages including easy harvesting from patients, stemness, and superior differentiation capacity. We fabricated lacuna-mimic hNC clusters based on the binding ability of TA. The hNC clusters were encapsulated in a hydrogel crosslinked by click chemistry between modified polyethylene glycol (PEG) and gelatin. The hNC clusters showed high viability and improved chondrogenic differentiation in click chemistry-based hydrogel. When we injected the hNC clusters in hydrogel into a rat osteochondral defect model, they resulted in successful regeneration of cartilage in immunohistochemical staining data. These results demonstrate the potential of the lacuna-mimic structure composed of hNC clusters and click chemistry-based hydrogel in cartilage regeneration in vivo.