title: The size of surface microstructures as an osteogenic factor in calcium phosphate ceramics.
abstract: The microporosity of calcium phosphate (CaP) ceramics has been shown to have an essential role in osteoinduction by CaP ceramics after ectopic implantation. Here we show that it is not the microporosity but the size of surface microstructural features that is the most likely osteogenic factor. Two tricalcium phosphate (TCP) ceramics, namely TCP-S and TCP-B, were fabricated with equivalent chemistry and similar microporosity but different sizes of surface microstructural features. TCP-S has a grain size of 0.99 ± 0.20 μm and a micropore size of 0.65 ± 0.25 μm, while TCP-B displays a grain size of 3.08 ± 0.52 μm and a micropore size of 1.58 ± 0.65 μm. In vitro, both cell proliferation and osteogenic differentiation were significantly enhanced when human bone marrow stromal cells were cultured on TCP-S without any osteogenic growth factors, compared to TCP-B ceramic granules. The possible involvement of direct contact between cells and the TCP ceramic surface in osteogenic differentiation is also shown with a trans-well culture model. When the ceramic granules were implanted in paraspinal muscle of dogs for 12 weeks, abundant bone was formed in TCP-S (21 ± 10% bone in the available space), whereas no bone was formed in any of the TCP-B implants. The current in vitro and in vivo data reveal that the readily controllable cue, i.e. the size of the surface microstructure, could be sufficient to induce osteogenic differentiation of mesenchymal stem cells, ultimately leading to ectopic bone formation in calcium phosphate ceramics.
authors.affiliation: Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands; Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, People's Republic of China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands; Xpand Biotechnology BV, Bilthoven, The Netherlands.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Luo
authors.affiliation: Xpand Biotechnology BV, Bilthoven, The Netherlands.
authors.forename: Davide
authors.initials: D
authors.lastname: Barbieri
authors.affiliation: Department of Medical Cell Biophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands.
authors.forename: Ana M C
authors.initials: AM
authors.lastname: Barradas
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands; Xpand Biotechnology BV, Bilthoven, The Netherlands; School of Engineering and Materials Science (SEMS), Queen Mary University of London, London E1 4NS, UK.
authors.forename: Joost D
authors.initials: JD
authors.lastname: de Bruijn
authors.affiliation: Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands.
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.affiliation: Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE Enschede, The Netherlands; Xpand Biotechnology BV, Bilthoven, The Netherlands. Electronic address: h.yuan@utwente.nl.
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000327:Adsorption; D000818:Animals; D001483:Base Sequence; D001846:Bone Development; D002130:Calcium Phosphates / Q000737:chemistry*; D002478:Cells, Cultured; D002516:Ceramics; D017931:DNA Primers; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D010012:Osteogenesis; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D002130:Calcium Phosphates; D017931:DNA Primers; C020243:calcium phosphate
keywords: Calcium phosphate; Mesenchymal stem cell; Microstructure; Osteogenesis; Surface topography