VEGF-A regulates angiogenesis during osseointegration of Ti implants via paracrine/autocrine regulation of osteoblast response to hierarchical microstructure of the surface

Andrew L. Raines, Michael B. Berger, Nehal Patel, Sharon L. Hyzy, Barbara D. Boyan, Zvi Schwartz

Research output: Contribution to journalArticle

3 Scopus citations


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-A165 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.

Original languageEnglish (US)
Pages (from-to)423-433
Number of pages11
JournalJournal of Biomedical Materials Research - Part A
Issue number2
StatePublished - Feb 1 2019



  • VEGF
  • angiogenesis
  • osseointegration
  • osteoblast
  • titanium

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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