Self-assembled porous microgel scaffold with layered drug release for efficient repair of osteochondral...

The difficulty in regenerating osteochondral defects lies in the reduced proliferation and premature hypertrophy of chondrocytes. By maintaining the phenotype of immature chondrocytes within the superficial layer of regenerated cartilage and replicating natural cartilage microstructure, the proliferation capacity of chondrocytes can be enhanced, ensuring a continuous cell supply for cartilage repair. Therefore, utilizing biomimetic scaffolds with spatial microenvironment specificity to simulate the natural layered microstructure of osteochondral tissue is a key focus. We have designed a three-layer porous microgel scaffold with spatiotemporal controlled release of bioactive factors. In vitro, this scaffold can induce directed differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and maintain chondrocyte phenotypes at various maturation stages. In an animal model of osteochondral defects, this scaffold promoted the repair of the layered microstructure of articular cartilage. We speculate that the regenerative effect of the three-layer hydrogel system may be attributed to the precisely directed differentiation of chondrocytes and the accurate distribution of the corresponding extracellular matrix (ECM), as revealed by mRNA transcriptome sequencing. This work provides insights into chondrogenesis controlled by the microenvironment and may offer strategies for reconstructing the layered microstructure of articular cartilage.