An injectable and degradable heterogeneous microgel assembly capable of forming a “micro-nest group” for cell condensation and cartilage regeneration

Abstract

Cell condensation, linking the migration and chondrogenic differentiation of MSCs, plays a crucial role in cartilage development. Current cartilage repair strategies are inadequately concerned with this process, leading to a suboptimal quality of regenerated cartilage. Inspired by the “nest flocks” structure of Social Weavers, a degradable heterogeneous microgel assembly (F/S-MA) is developed, which can release SDF-1, to form a “micro-nest group” structure and bond with HAV peptides to promote cell recruitment, condensation and chondrogenic differentiation. First, slow-degrading microgels (S-microgels) grafted with HAV peptides and fast-degrading microgels (F-microgels) loaded with SDF-1 are fabricated by an amidation reaction and Schiff base reaction, respectively. They employ sulfhydryl-modified gelatin as assembling agents to form F/S-MA through a thiol–ene reaction, exhibiting injectability, tissue adhesion, and microporosity. F-microgels undergo rapid degradation, leading to the release of SDF-1 and the formation of a “micro-nest group” in F/S-MA. Consequently, F/S-MA exhibits cell recruitment ability, meanwhile facilitating BMSC condensation through the synergistic effects of the “micro-nest group” and HAV peptides. In vitro experiments prove that F/S-MA enhances the expression of cell-condensation-related markers, ultimately upregulating the secretion of cartilage matrix. Animal experiments show that F/S-MA optimizes the quality of regenerated cartilage by improving cell recruitment and condensation. F/S-MA enhances cell condensation through structural and component design, which will provide new insights for cartilage regeneration.