title: Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo.
abstract: 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.
authors.affiliation: Xpand Biotechnology BV, 3723 MB Bilthoven, The Netherlands.Noel.Davison@Xpand-Biotech.com.
authors.forename: N L
authors.initials: NL
authors.lastname: Davison
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: T
authors.initials: T
authors.lastname: Schoenmaker
authors.forename: V
authors.initials: V
authors.lastname: Everts
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: F
authors.initials: F
authors.lastname: Barrère-de Groot
authors.forename: J D
authors.initials: JD
authors.lastname: de Bruijn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D004285:Dogs; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000601:surgery; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis
chemical_list: D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate