Bone response to biomimetic implants delivering BMP-2 and VEGF: an immunohistochemical study

J Craniomaxillofac Surg. 2013 Dec;41(8):826-35. doi: 10.1016/j.jcms.2013.01.037. Epub 2013 Feb 21.


This animal study evaluated bone healing around titanium implant surfaces biomimetically coated with bone morphogenic protein-2 (BMP-2) and/or vascular endothelial growth factor (VEGF) by examining bone matrix proteins and mineralisation. Five different implant surfaces were established: acid-etched surface (AE), biomimetic calcium phosphate surface (CAP), BMP-2 loaded CAP surface, VEGF loaded CAP surface and dual BMP-2 + VEGF loaded CAP surface. The implants were inserted into calvariae of adult domestic pigs. For the comparison of osteoconductive capacity of each surface, bone mineral density and expression of bone matrix proteins (collagen I, BMP-2/4, osteocalcin and osteopontin) inside defined chambers around the implant were assessed using light microscopy and microradiography and immunohistochemical analysis at 1, 2 and 4 weeks. In the both groups delivering BMP-2, the bone mineral density was significantly enhanced after 2 weeks and the highest value was measured for the group BMP + VEGF. In the group VEGF, collagen I and BMP-2/4 expressions were significantly up-regulated at the first and second weeks. The percentage of BMP-2/4 positive cells in the group BMP + VEGF was significantly enhanced compared with the groups AE and CAP at the second week. Although the highest osteocalcin and osteopontin expression values were observed for the group BMP + VEGF after 2 weeks, no statistically significant difference in osteocalcin and osteopontin expressions was found between all groups at any time. It was concluded that combined delivery of BMP-2 and VEGF favoured bone mineralisation and expression of important bone matrix proteins that might explain synergistic interaction between both growth factors.

Keywords: Biomimetic; Bone; Bone morphogenic protein (BMP); Immunohistochemistry; Osteoconductivity; Vascular endothelial growth factor (VEGF).

Publication types

  • Comparative Study

MeSH terms

  • Acid Etching, Dental / methods
  • Animals
  • Biomimetic Materials / chemistry*
  • Bone Density / drug effects
  • Bone Matrix / drug effects
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Calcification, Physiologic / drug effects
  • Calcium Phosphates / chemistry
  • Coated Materials, Biocompatible / chemistry*
  • Collagen Type I / drug effects
  • Dental Implants
  • Dental Materials / chemistry
  • Dental Prosthesis Design
  • Female
  • Immunohistochemistry
  • Microradiography
  • Microscopy, Electron, Scanning
  • Osteocalcin / drug effects
  • Osteogenesis / drug effects
  • Osteopontin / drug effects
  • Skull / drug effects*
  • Surface Properties
  • Swine
  • Time Factors
  • Titanium / chemistry
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / pharmacology*


  • Bone Morphogenetic Protein 2
  • Calcium Phosphates
  • Coated Materials, Biocompatible
  • Collagen Type I
  • Dental Implants
  • Dental Materials
  • Vascular Endothelial Growth Factor A
  • Osteocalcin
  • Osteopontin
  • calcium phosphate
  • Titanium