Bone marrow stromal cells enhance the osteogenic properties of hydroxyapatite scaffolds by modulating the foreign body reaction.

We aimed to investigate the osteogenic properties of bone marrow stromal cell (BMSC)-loaded biomimetic constructs composed of hydroxyapatite (HA), with or without in vitro cell-derived extracellular matrix (HA-ECM), and to assess the cellular components of the elicited foreign body reaction. HA-ECM constructs were produced by adult rat dermal fibroblasts cultured on top of synthetic HA microparticles. Rat calvarial critical-sized defects (8 mm) were created and treated with the generated HA-ECM constructs or HA microparticles, alone or combined with green fluorescent protein (GFP)-expressing BMSCs. The new bone formation and the local cellular inflammatory response (macrophages, neutrophils, lymphocytes, eosinophils and PCNA-index) were assessed by histomorphometry and immunohistochemistry at 2 and 12 weeks postoperatively. In addition, the BMSCs' survival and engraftment were checked. The largest volume of the newly formed bone was found in defects treated with HA-ECM constructs combined with BMSCs (p < 0.05). Moreover, the implanted BMSCs modulated the local inflammatory response, demonstrated by either a significant increase (HA vs HA + BMSCs) or decrease (HA-ECM vs HA-ECM + BMSCs) of the inflammatory cell number. No donor BMSCs were detected at the site of implantation or in the host bone marrow at 2 or 12 weeks postoperatively. In conclusion, the treatment of critical-sized calvarial defects with the BMSC-loaded biomimetic constructs has significantly enhanced bone repair by modulating the foreign body reaction. Our findings highlight the implications of BMSCs in the regulation of the foreign body reaction triggered by tissue-engineered constructs, proving a higher efficiency for the BMSC combination therapy.