Functional injectable hydrogel with spatiotemporal sequential release for recruitment of endogenous stem cells and <i>in situ</i> cartilage regeneration

Abstract

Articular cartilage is refractory to self-healing due to the absence of vascular, nervous, and lymphatic systems, and its repair remains a clinical challenge. Tissue regeneration through <i>in situ</i> recruitment of stem cells <i>via</i> cell-free scaffolds is a promising alternative strategy. Herein, a kind of functional injectable hydrogel system (Col-Apt@KGN MPs), which is a collagen-based and microsphere-embedded cell-free scaffold, was designed to achieve spatiotemporal regulation of endogenous mesenchymal stem cells (MSCs) recruitment and their chondrogenic differentiation by respective release of aptamer 19S (Apt19S) and kartogenin (KGN). <i>In vitro</i> results confirmed that the Col-Apt@KGN MPs hydrogel had sequential release characteristics. Apt19S was rapidly released from the hydrogel within 6 days, while KGN was slowly released for 33 days <i>via</i> the degradation of poly(lactic-<i>co</i>-glycolic acid) (PLGA) microspheres. When cultured with MSCs, the Col-Apt@KGN MPs hydrogel supported the adhesion, proliferation, and chondrogenic differentiation of MSCs. <i>In vivo</i> results indicated that the Col-Apt@KGN MPs hydrogel effectively promoted the recruitment of endogenous MSCs in a rabbit full-thickness cartilage defect model; furthermore, the Col-Apt@KGN MPs hydrogel enhanced the secretion of cartilage specific extracellular matrix and achieved the reconstruction of subchondral bone. This study demonstrates that the Col-Apt@KGN MPs hydrogel possesses great potential in recruitment of endogenous stem cells and cartilage tissue regeneration.