A novel protocol for injectable artificial cartilage constructs based on programmed shape-morphing hydrogels for cartilage regeneration

Direct contact between cells is of great significance to the formation of natural tissues, especially in regard to cartilage differentiation, which begins with the biological process of cell aggregation. Herein, based on the preparation of microspheres via microwells, we prepared functional hydrogel-based microwells by using cobalt ionic crosslinking. The preparation of functional microwells can not only induce the upregulation of genes and proteins related to cartilage differentiation but also greatly reduce markers related to hypertrophy and mineralization, which play a significant role in the formation of hyaline cartilage. Importantly, we combined microwell cultures with the later preparation of injectable artificial cartilage grafts. In vitro, microwell culture and cartilage differentiation induction can be achieved through the preparation of microwells crosslinked by ions. Via the partial removal of ions, the hydrogel and microtissues can be injected into the defect through the shape recovery of the gel in the later stage and through the stable gel formed by covalent crosslinking to repair irregular cartilage defects. This study not only broadens the application of microwells but also promotes the progress of material-based tissue engineering strategies through the design of intelligent materials.