Enhanced osteogenic protein expression on human osteoblast-osteoclast co-culture system using doped hydroxyapatite plasma coatings for orthopedic and dental applications

Abstract

For decades, research has been attributed to the monoculture of either mesenchymal stem cells (MSCs) or monocytes to differentiate into osteoblasts (OBs) and osteoclasts (OCs) respectively, however, this is far from being realistic. For improved research in the field of biomaterials, the balance between OBs and OCs needs to be investigated simultaneously on in vitro models for a better understanding and prediction of the bone remodeling process in vivo. The study aims to investigate the effects of Mg+2 and Sr+2 dopant in hydroxyapatite coating on the simultaneous differentiation of human MSCs and Tamm Horsfall Protein 1 (THP-1) monocytes into OBs and OCs respectively. We hypothesize that a cultivation regime can be established to show simultaneous proliferation and differentiation of the MSCs and monocytes into OBs and OCs. Also, the presence of Sr+2 and Mg+2 will induce faster bone remodeling and demonstrate enhanced osteogenic properties. Doped hydroxyapatite coatings were fabricated on CpTi substrates using plasma spray coating technique and the influence of dopants on the in vitro OB−OC co-culture was studied by specific marker genes, namely OPG, RANKL, RUNX2, and ACP5. Comparison amongst the expressions of genes reveals the differentiation of the primary cells as early as 5-day time-point. Downregulation of RUNX2 and ACP5 in the doped HA coated samples at 15-day time-point are a proof of the effective role of the dopants in the enhancement of bone remodeling. This study shows the possibility of simultaneous culturing of human OB and OC precursors and demonstrates the efficacy of dopants in the pace change of bone remodeling for bone tissue engineering applications.