Abstract
The combination of mesenchymal stromal cells (MSCs) with active injectable carriers brings about innovative solutions to current issues in the field of tissue engineering. In particular, repair of adult articular cartilage lesions, especially those affecting the knee, remains a clinical challenge because of the limited cartilage self-healing capacity. A previous work of our team demonstrated that the open porosity of homemade collagen microspheres allowed for the entrapment and progressive release of TGF-β3, which efficiently triggered the chondrogenic differentiation of MSCs in vitro and in vivo, and the production of neo-cartilage tissue [1]. However, one major hurdle in MSC-based therapies for cartilage repair is their late hypertrophic differentiation and subsequent tissue calcification.In this context, we identified Runx2 protein, which plays a central role in chondrocyte hypertrophy, as the main molecular target to be repressed. We developed a new siRNA nanovector that showed interesting properties, such as tunable size, stability in cell culture conditions and high efficiency to transfect primary human MSCs [2]. After entrapment of nanovectors in porous collagen microspheres, we showed their size influenced both loading capacity and release kinetics. These different release profiles led to differences in the transfection kinetics of human MSCs. This original and unique type of gene activated matrix, with adaptable release kinetics, is one step forward in the control of MSC differentiation, and must allow future advances in the treatment of osteoarthritis and other cartilages lesions.References[1] Mathieu et al., 2014. Eur Cell Mater 28, 82–96; discussion 96-97. https://doi.org/10.22203/ecm.v028a07[2] Salvador et al., 2022. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2022.09.016