Résumé
Repair of adult knee cartilage lesions remains a clinical challenge because of the limited cartilage self-healing capacity. A previous work of our team demonstrated that TGF-β3 could be entrapped in homemade collagen microspheres, and released progressively, which triggered the chondrogenic differentiation of MSCs in vitro and in vivo, and the production of neo-cartilage tissue. However, MSCs tend to show late hypertrophic differentiation, and subsequent tissue calcification. Thus, we identified Runx2 protein, which plays a central role in chondrocyte hypertrophy, as a molecular target to be repressed. We developed a siRNA nanovector, with tunable size, stability in cell culture conditions and high efficiency to transfect primary human MSCs. After entrapping vectors in porous collagen microspheres, we showed their size influenced both loading capacity and release kinetics, which led to differences in the transfection kinetics of human MSCs. This gene activated matrix must allow the control of MSC differentiation, and future advances in the treatment of cartilages lesions.