title: The synergistic effect of VEGF and biomorphic silicon carbides topography on in vivo angiogenesis and human bone marrow derived mesenchymal stem cell differentiation.
abstract: Topographical features of biomaterials are able to modulate cell attachment, spreading and differentiation. The addition of growth factors to implantable biomaterials can modify these cellular responses, enhancing their therapeutic potential. The aim of this research is to establish the influence of biomorphic silicon carbide ceramics (bioSiCs) surface topography on the proliferation and osteoblastic differentiation of mesenchymal stem cells and the potential synergistic effect of the ceramic porous structure together with vascular endothelial growth factor loading (VEGF) on the surface mediated osteoblastic differentiation. Three porous bioSiCs with important differences in their microstructure were obtained from different natural precursors. Samples loaded with or without VEGF through ionic interactions were cultured with human umbilical vein endothelial cells (HUVEC) or bone marrow derived mesenchymal stem cells (hMSCs). Cell behaviour and protein activity with regard to bioSiC porous structure and surface properties were analysed. An in vivo model (Chick Chorioallantoic Membrane; CAM) was used to assess the capability of the VEGF loaded systems to promote angiogenesis. Experimental data show that loaded systems were able to control the release of VEGF for up to 15 d ensuring the activity of the protein, increasing the proliferation of HUVECs and the formation of new blood vessels in the CAM. It was found that the selection of bioSiCs with a higher pore size promoted a higher concentration of osteoblastic differentiation markers of MSCs cultured on the surface of bioSiCs. Furthermore, the addition of VEGF to the systems was able to promote a faster osteoblastic differentiation according to the qPCR results, suggesting a synergy between both the surface properties and the controlled release of the growth factor. The VEGF loaded sapelli bioSiC was found to be the most promising material for bone tissue engineering applications.
authors.affiliation: Dpto. Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Díaz-Rodríguez
authors.forename: J L
authors.initials: JL
authors.lastname: Gómez-Amoza
authors.forename: M
authors.initials: M
authors.lastname: Landin
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017554:Carbon Compounds, Inorganic / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016062:Porosity; D017655:Silicon Compounds / Q000737:chemistry; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D017554:Carbon Compounds, Inorganic; D004343:Drug Implants; D017655:Silicon Compounds; D042461:Vascular Endothelial Growth Factor A; C022088:silicon carbide