Fabrication of an injectable hydrogel scaffold embedding kartogenin-encapsulated PLGA microsphere with long-term drug release to promote chondrogenesis

To address the long-lasting challenges on repair of articular cartilage defects in clinic, cartilage tissue engineering (CTE) strategy aims to develop favorable scaffolds to undertake mechanical support and simulate the cellular microenvironment for remodeling or replacing the defective cartilage tissues. Wherein, facile operation, favorable mechanical strength, excellent biocompatibility, suitable biodegradability, and innate chondrogenic ability are crucially adjective in CTE. Herein, we fabricated an injectable tetra-PEG hydrogel scaffold embedding kartogenin-encapsulated poly (lactic-co-glycolic acid) (PLGA@KGN) microspheres by means of the premix membrane emulsification (PME) method and quick sol-gel transformation. The unform tetra-PEG network endowed this composite hydrogel (tetra-PEG/PLGA@KGN) with favorable pores, easy injectability, mechanical strength and lower swelling ratio, while the internal small KGN drugs with the unique differentiation ability into chondrocytes could be slowly released for a long period of time, thus capably allowing the maintenance of the drug's effective concentration and long-lasting sustained release up to >28 days and persistently enhancing its chondrogenic efficiency. In vitro results indicated its satisfactory compatibility for supporting the cell activity, proliferation, and differentiation. Overall, due to improved mechanical property and sustainable KGN release behavior, this designable hydrogel scaffold may provide an option with clinical translational potential for cartilage repair.