Subchondral bone repair potential of an osteochondral scaffold augmented with BMP-2 or strontium-enriched amorphous calcium phosphate: a co-culture in vitro model

Purpose: the osteoinductive potential of two different augmentation strategies: the addition of Bone Morphogenetic Protein-2 (BMP-2) or the incorporation of strontium ions-enriched amorphous calcium phosphate (Sr-ACP) granules. Methods: Human mesenchymal stromal cells (MSCs) were seeded on the differently modified scaffolds and unmodified material used as a control, and grown for 14 days in a co-culture system in the presence of primary osteoclasts and conditioned medium of endothelial cells. The potential of the BMP-2- and Sr-ACP-enriched scaffolds compared to the control was then evaluated in terms of MSCs adhesion and morphology, metabolic activity, osteogenic differentiation, and osteoclasts' markers expression. Results: Morphologically, both modified scaffolds sustained good cell adhesion. More secreted matrix was observed on the BMP-2 scaffold, together with higher metabolic activity and an upregulation of most of the evaluated osteoblast-related genes compared to the control and the Sr-ACP scaffold. Conversely, in the presence of the Sr-ACP scaffold, lower metabolic activity and a slower activation of osteoblast-related markers, together with a tendency to stimulate the osteoclasts' activity, was observed. Conclusion: Overall, both augmentation strategies were able to favor the adhesion and growth of MSCs compared to the unmodified scaffold, with the BMP-2-modified scaffold promoting more the differentiation of MSCs toward a mature osteoblastic phenotype than the Sr-ACP-modified scaffold, and the latter promoting more osteoclast activation.