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VEGF‐A regulates angiogenesis during osseointegration of Ti implants via paracrine/autocrine regulation of osteoblast response to hierarchical microstructure of the surface
Author(s) -
Raines Andrew L.,
Berger Michael B.,
Patel Nehal,
Hyzy Sharon L.,
Boyan Barbara D.,
Schwartz Zvi
Publication year - 2019
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36559
Subject(s) - materials science , autocrine signalling , paracrine signalling , osseointegration , angiogenesis , osteoblast , microstructure , microbiology and biotechnology , biomedical engineering , cancer research , implant , composite material , biology , medicine , in vitro , biochemistry , receptor , surgery
Establishment of a patent vasculature at the bone–implant interface plays a significant role in determining overall success of orthopedic and dental implants. Osteoblasts produce vascular endothelial growth factor‐A (VEGF‐A), an important regulator of angiogenesis during bone formation and healing, and the amount secreted is sensitive to titanium (Ti) surface microtopography and surface energy. The purpose of this study was to determine if surface properties modulate cellular response to VEGF‐A. MG63 osteoblast‐like cells were transfected with shRNA targeting VEGF‐A at >80% knockdown. Cells stably silenced for VEGF‐A secreted reduced levels of osteocalcin, osteoprotegerin, FGF‐2, and angiopoietin‐1 when cultured on grit‐blasted/acid‐etched (SLA) and hydrophilic SLA (modSLA) Ti surfaces and conditioned media from these cultures caused reduced angiogenesis in an endothelial tubule formation assay. Treatment of MG63 cells with 20 ng/mL rhVEGF‐A 165 rescued production in silenced cells and increased production of osteocalcin, osteoprotegerin, FGF‐2, and angiopoietin‐1, with greatest effects on control cells cultured on modSLA. Addition of a neutralization antibody against VEGF receptor 2 (VEGFR2; Flk‐1) resulted in a significant increase in VEGF‐A production. Overall, this study indicates that VEGF‐A has two roles in osseointegration: enhanced angiogenesis and an autocrine/paracrine role in maturation of osteoblast‐like cells in response to Ti surface properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 423–433, 2019.