Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects

J Periodontol. 2003 Jun;74(6):787-97. doi: 10.1902/jop.2003.74.6.787.

Abstract

Background: Bone morphogenetic proteins (BMPs) are being evaluated as candidates for periodontal and bone regenerative therapy. However, the research on recombinant human bone morphogenetic protein-4 (rhBMP-4) has been insufficient to evaluate its capacity to enhance bone formation and its carrier system. The purpose of this study was to evaluate the bone regenerative effect of rhBMP-4 delivered with an absorbable collagen sponge (ACS) or beta-tricalcium phosphate (beta-TCP). We also compared the potential of beta-TCP to that of ACS as a carrier system for rhBMP-4.

Methods: Eight-mm calvarial critical-sized defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 groups of 20 animals each. The defects were treated with rhBMP-4/ACS (rhBMP-4 at 0.05 mg/ml), rhBMP-4/beta-TCP (rhBMP-4 at 0.05 mg/ml), ACS alone, beta-TCP alone, or left untreated for surgical control. The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated radiodensitometrically, histologically, and histomorphometrically.

Results: The results of radiodensitometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups were more radiopaque than other groups at both 2 and 8 weeks (P < 0.01). The histologic observations were as follows: in the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups, new bone was evident at the defect sites at 2 weeks and 8 weeks. The results of histomorphometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups had more bone (%) than other groups at both 2 and 8 weeks (P < 0.01).

Conclusions: Surgical implantation of rhBMP-4/ACS may be used to support bone regeneration in the rat calvarial critical-sized defect, and rhBMP-4/beta-TCP may be able to regenerate bone in the rat calvarial critical-sized defect without complication. In addition, both ACS and beta-TCP may be considered as available carriers for rhBMP-4.

Publication types

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

MeSH terms

  • Absorptiometry, Photon
  • Animals
  • Biocompatible Materials
  • Bone Density / drug effects
  • Bone Diseases / drug therapy*
  • Bone Diseases / pathology
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / administration & dosage
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bone Regeneration / drug effects*
  • Calcium Phosphates
  • Drug Carriers
  • Gelatin Sponge, Absorbable
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Skull / drug effects*
  • Skull / pathology

Substances

  • BMP4 protein, human
  • Biocompatible Materials
  • Bmp4 protein, rat
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Calcium Phosphates
  • Drug Carriers
  • Recombinant Proteins
  • beta-tricalcium phosphate
  • tricalcium phosphate