Thermosensitive Injectable Gradient Hydrogel-Induced Bidirectional Differentiation of BMSCs

Osteochondral defects threaten the quality of life of patients to a great extent. To simulate gradient changes in osteochondral tissue, a gradient-mixing injection device consisting of a controller and injection pumps is design. Bioactive glass (BG) and gellan gum (GG) are used to prepare thermosensitive injectable gradient hydrogels (B_0.5 G, B₁ G) with an upper critical solution temperature (UCST) range of 37.7-40.2 °C using this device for the first time. The mechanical properties of gradient hydrogels are significantly better than those of pure GG hydrogels. The gradients in the composition, structure, and morphology of gradient hydrogels are confirmed via physicochemical characterization. Cytocompatibility tests show that hydrogels, especially B_0.5 G gradient hydrogels, promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). Most importantly, qRT-PCR shows that the different components in B_0.5 G gradient hydrogels simultaneously induce the osteogenic and chondrogenic differentiation of BMSCs. Experimental injection in porcine osteochondral defects indicates that the B_0.5 G gradient hydrogel seamlessly fills irregular osteochondral defects in a less invasive manner by controlling the temperature to avoid cellular and tissue damage arising from crosslinkers or other conditions. These results show that thermosensitive injectable B_0.5 G gradient hydrogels have the potential for less invasive integrated osteochondral repair.