In Situ Articular Cartilage Regeneration through Endogenous Reparative Cell Homing Using a Functional Bone Marrow-Specific Scaffolding System

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA)₄-CONH₂/Ac-(RADA)₄GGSKPPGTSS-CONH₂ (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior hyaline-like cartilage repair and successful subchondral bone reconstruction. By contrast, the control groups mostly led to fibrous tissue repair. These findings indicate that the DCM-RAD/SKP can recruit endogenous stem cells into the site of cartilage injury and promote differentiation of the infiltrating cells into the chondrogenic lineage, holding great potential as a one-step surgery strategy for cartilage repair.