Mesenchymal stem cells (MSCs) have been widely investigated to repair injured cartilage tissues for the treatment of arthritis. Despite these great efforts, the difficulty in the spatiotemporal control of delivered cells has limited the further clinical development with rapid clearance. Here, we developed injectable hyaluronate (HA) hydrogels to encapsulate MSCs for controlled cartilage tissue regeneration based on the supramolecular chemistry between β-cyclodextrin-modified HA (HA-CD) and adamantane (Ad)-modified HA (HA-Ad). Supramolecular HA hydrogels exhibited remarkable mechanical characteristics such as shear thinning and self-healing with a high cell viability of encapsulated MSCs. The spatiotemporally controlled delivery of MSCs from the supramolecular HA hydrogels resulted in the statistically significant chondrogenic differentiation and extracellular matrix deposition in vitro and in vivo. We could confirm the notable cartilage tissue regeneration in cartilage defect model rats after treatment with supramolecular HA hydrogels encapsulating MSCs for 28 days. Taken together, supramolecular HA hydrogels would be successfully harnessed as an injectable delivery system of MSCs for cartilage tissue regeneration and other tissue engineering applications.
Keywords: cartilage tissue regeneration; cell therapy; hyaluronate; mesenchymal stem cell; supramolecular hydrogel.