CaAlg hydrogel containing bone morphogenetic protein 4-enhanced adipose-derived stem cells combined with osteochondral mosaicplasty facilitated the repair of large osteochondral defects.

Abstract

Cartilage repair presents a challenge to clinicians and researchers. A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage. In the present study, we aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs). ADSCs were transduced with BMP4 (B-ADSCs). The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA). Swine models of large cartilage defects of the knee were constructed and received one of the four treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks. Outcomes were evaluated at 12 and 24weeks after surgery. The in vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control. In vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface. Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups. Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage. Mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of one-stage complete repair surgery for large osteochondral defects. This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.