Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo

A current challenge of synthetic bone graft substitute design is to induce bone formation at a similar rate to its biological resorption, matching bone's intrinsic osteoinductivity and capacity for remodelling. We hypothesise that both osteoinduction and resorption can be achieved by altering surface microstructure of beta-tricalcium phosphate (TCP). To test this, two TCP ceramics are engineered with equivalent chemistry and macrostructure but with either submicron- or micron-scale surface architecture. In vitro, submicron-scale surface architecture differentiates larger, more active osteoclasts--a cell type shown to be important for both TCP resorption and osteogenesis--and enhances their secretion of osteogenic factors to induce osteoblast differentiation of human mesenchymal stem cells. In an intramuscular model, submicrostructured TCP forms 20 % bone in the free space, is resorbed by 24 %, and is densely populated by multinucleated osteoclast-like cells after 12 weeks; however, TCP with micron-scale surface architecture forms no bone, is essentially not resorbed, and contains scarce osteoclast-like cells. Thus, a novel submicron-structured TCP induces substantial bone formation and is resorbed at an equivalent rate, potentially through the control of osteoclast-like cells.