Comparison of 5 BMPs for their chondrogenic potentials and microfracture-mediated cartilage repair using heparin/PEAD coacervate sustained release polymer

Cartilage defect repair and osteoarthritis treatments remain clinical challenges. Microfracture is a commonly used surgical procedure for the treatment of cartilage defects but often leads to fibrocartilage repair. The aim of this study is to compare the effects of 5 bone morphogenetic proteins (BMPs) on chondrogenic differentiation of human bone marrow mesenchymal stem cells, as well as to investigate the use of the heparin/poly (ethylene arginine aspartate diglyceride (PEAD) coacervate sustained release system to deliver these BMPs for microfracture-mediated cartilage repair. Our results indicate that all 5 human BMPs significantly enhance the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs) with BMPs 2,4 and 9 being more potent than BMP6 or BMP7, as revealed by Alcian blue, SO staining, and immunohistochemistry of COL2. Coacervate-BMPs are biocompatible for both hBMMSCs and rat muscle-derived stem cells (MDSCs) and promote their proliferation. <i>In vivo</i>, sustained release of human BMPs 2,4,6,7,9 with heparin/PEAD coacervate significantly enhances microfracture-mediated cartilage repair in a rat osteochondral defect model, as demonstrated by ICRS macroscopic score, Seller's histology score, and COL2 staining. These effects are mediated by increasing SOX9 expression in the regenerated cartilage. In conclusion, BMPs 2,4,9 are the most potent BMPS to promote chondrogenic differentiation, while all BMPs enhanced microfracture-mediated cartilage repair when delivered with heparin/PEAD coacervate without a significant difference between the different BMPs.