Interactions between endothelial progenitor cells (EPC) and titanium implant surfaces

Clin Oral Investig. 2013 Jan;17(1):301-9. doi: 10.1007/s00784-012-0691-7. Epub 2012 Mar 10.


Objectives: Endothelial cells play an important role in peri-implant angiogenesis during early bone formation. Therefore, interactions between endothelial progenitor cells (EPCs) and titanium dental implant surfaces are of crucial interest. The aim of our in vitro study was to investigate the reactions of EPCs in contact with different commercially available implant surfaces.

Materials and methods: EPCs from buffy coats were isolated by Ficoll density gradient separation. After cell differentiation, EPC were cultured for a period of 7 days on different titanium surfaces. The test surfaces varied in roughness and hydrophilicity: acid-etched (A), sand-blasted-blasted and acid-etched (SLA), hydrophilic A (modA), and hydrophilic SLA (modSLA). Plastic and fibronectin-coated plastic surfaces served as controls. Cell numbers and morphology were analyzed by confocal laser scanning microscopy. Secretion of vascular endothelial growth factor (VEGF)-A was measured by enzyme-linked immunosorbent assay and expressions of iNOS and eNOS were investigated by real-time polymerase chain reaction.

Results: Cell numbers were higher in the control groups compared to the cells of titanium surfaces. Initially, hydrophilic titanium surfaces (modA and modSLA) showed lower cell numbers than hydrophobic surfaces (A and SLA). After 7 days smoother surfaces (A and modA) showed increased cell numbers compared to rougher surfaces (SLA and modSLA). Cell morphology of A, modA, and control surfaces was characterized by a multitude of pseudopodia and planar cell soma architecture. SLA and modSLA promoted small and plump cell soma with little quantity of pseudopodia. The lowest VEGF level was measured on A, the highest on modSLA. The highest eNOS and iNOS expressions were found on modA surfaces.

Conclusions: The results of this study demonstrate that biological behaviors of EPCs can be influenced by different surfaces. The modSLA surface promotes an undifferentiated phenotype of EPCs that has the ability to secrete growth factors in great quantities.

Clinical relevance: In correlation with recent clinical studies these results underline the hypothesis that EPC could promote and increase neovascularization by secreting paracrine factors which support osseointegration of dental implants.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Etching, Dental / methods
  • Cell Count
  • Cell Culture Techniques
  • Cell Differentiation / physiology
  • Cell Shape
  • Coated Materials, Biocompatible / chemistry
  • Dental Etching / methods
  • Dental Implants*
  • Dental Materials / chemistry*
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / cytology*
  • Fibronectins / chemistry
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type III / analysis
  • Osseointegration / physiology
  • Phenotype
  • Polystyrenes / chemistry
  • Stem Cells / physiology*
  • Surface Properties
  • Titanium / chemistry*
  • Vascular Endothelial Growth Factor A / analysis


  • Coated Materials, Biocompatible
  • Dental Implants
  • Dental Materials
  • Fibronectins
  • Polystyrenes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Titanium
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III