Ectopic bone formation associated with recombinant human bone morphogenetic proteins-2 using absorbable collagen sponge and beta tricalcium phosphate as carriers

Biomaterials. 2005 May;26(15):2501-7. doi: 10.1016/j.biomaterials.2004.07.015.


The ectopic bone formation of recombinant human bone morphogenetic protein-2(rhBMP-2) was evaluated using absorbable collagen sponges (ACS) and beta tricalcium phosphate (beta-TCP) as carriers in a rat subcutaneous assay model. Subcutaneous pockets were created on the back of rats. The pockets were implanted with rhBMP-2/ACS, rhBMP-2/beta-TCP, ACS alone, and beta-TCP alone. The rats were sacrificed at 2 or 8 weeks for histological and immunohistochemical evaluation. At 2 weeks, bone formation was evident in both the rhBMP-2/ACS and rhBMP-2/beta-TCP sites. At 8 weeks, the quantity of the new bone with a more advanced stage of remodeling had increased further in the rhBMP-2/beta-TCP sites. However, the newly formed bone observed at 2 weeks was not found in the rhBMP-2/ACS sites. On immunohistochemical observation, osteopontin staining was observed on both the rhBMP-2/ACS (2 weeks) and rhBMP-2/beta-TCP (2 and 8 weeks) sites. Osteocalcin was not detected in any of the samples. The lack of space-providing capacity of ACS may be one of the major factors responsible for its failure to maintain the newly induced bone. Therefore, a carrier for BMPs should provide space for bone formation and maturation during the more advanced healing stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Absorption
  • Animals
  • Biocompatible Materials / chemistry
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Substitutes / administration & dosage
  • Bone Substitutes / chemistry*
  • Bone and Bones / cytology
  • Bone and Bones / drug effects*
  • Calcium Phosphates / chemistry*
  • Choristoma / pathology
  • Collagen / chemistry*
  • Drug Carriers / chemistry*
  • Drug Implants / administration & dosage
  • Male
  • Materials Testing
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering
  • Transforming Growth Factor beta / administration & dosage*


  • BMP2 protein, human
  • Biocompatible Materials
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Bone Substitutes
  • Calcium Phosphates
  • Drug Carriers
  • Drug Implants
  • Transforming Growth Factor beta
  • beta-tricalcium phosphate
  • Collagen