Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffold improves subchondral bone repair

Abstract

To date, osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair has been suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed at improving the bone repair potential of this scaffold by incorporating strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 {micro}m). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 {+/-} 0.04 wt.%. Then 30 wt.% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well distributed and embedded in the collagenic matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed in in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of both ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold only in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.