Beta-tricalcium phosphate ceramic triggers fast and robust bone formation by human mesenchymal stem cells

J Tissue Eng Regen Med. 2019 Jun;13(6):1007-1018. doi: 10.1002/term.2848. Epub 2019 Apr 15.

Abstract

Due to their osteoconductive and inductive properties, a variety of calcium phosphate (CaP) scaffolds are commonly used in orthopaedics as graft material to heal bone defects. In this study, we have used two CaP scaffolds with different hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) ratios (MBCP®; 60/40 and MBCP+ ®; 20/80) to investigate their intrinsic capacity to favour human bone marrow stem cells (hBMSCs) osteogenic differentiation capacity. We report that MBCP+ ® showed in in vitro culture model a higher rate of calcium ion release in comparison with MBCP®. In two defined coculture systems, the hBMSC seeded onto MBCP+ ® presented an increased amount of VEGF secretion, resulting in an enhanced endothelial cell proliferation and capillary formation compared with hBMSC seeded onto MBCP®. When both ceramics combined with hBMSC were implanted in a nude mouse model, we observed a faster osteogenic differentiation and enhancement mature bone deposition sustained by the presence of a vast host vasculature within the MBCP+ ® ceramics. Bone formation was observed in samples highly positive to the activation of calcium sensing receptor protein (CaSr) on the surface of seeded hBMSC that also shown higher BMP-2 protein expression. With these data we provide valuable insights in the possible mechanisms of ossification and angiogenesis by hBMSC that we believe to be primed by calcium ions released from CaP scaffolds. Evidences could lead to an optimization of ceramic scaffolds to prime bone repair.

Keywords: calcium phosphate; osteogenesis; regenerative medicine; vascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Calcium Phosphates / pharmacology*
  • Cell Differentiation
  • Cell Proliferation / drug effects
  • Ceramics / pharmacology*
  • Durapatite / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice, Nude
  • Neovascularization, Physiologic / drug effects
  • Osteogenesis / drug effects*
  • Receptors, Calcium-Sensing / metabolism
  • Signal Transduction
  • Tissue Engineering

Substances

  • Bone Morphogenetic Protein 2
  • Calcium Phosphates
  • Receptors, Calcium-Sensing
  • beta-tricalcium phosphate
  • Durapatite