Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene glycol copolymer-tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2

Biomaterials. 2006 Jul;27(21):3927-33. doi: 10.1016/j.biomaterials.2006.03.013. Epub 2006 Mar 24.

Abstract

A new putty-like material with bone-inducing capacity was made by combining a block copolymer of poly d,l-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) and beta-tricalcium phosphate (beta-TCP) powder with added recombinant human bone morphogenetic protein-2 (rhBMP-2). To optimize the material's efficacy for bone formation, we formulated the optimal composition ratio of the respective constituent that gives the greatest osteoinductive efficacy in a mouse model of ectopic bone formation. In this series of studies, we investigated the size of ectopic bone mass induced 3 and 6 weeks after implantation of the materials composed of 30 mg of PLA-DX-PEG with 2 microg of rhBMP-2 and 0, 15, 30, or 60 mg of beta-TCP powder. An additional experiment was designed to investigate how content ratios of beta-TCP powder in 30 mg-putty implants (0%, 16.7%, 33.3%, 50%, 66.7%, 83.3%, or 100%) for a fixed dose (5 microg) of the rhBMP-2 altered the size of the induced ossicle. The results from the first experiment indicated that the bone yields were linearly dependent on the amount of additional beta-TCP powder. In the second experiment, the largest ossicles induced by 5 microg of rhBMP-2 were obtained when the polymer/beta-TCP ratio was 1/2 in mice. The data provide important insights into the fabrication of implants that provide efficacious delivery of rhBMP-2. The new putty-like material may be valuable for repairing or regenerating bone in a clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Morphogenetic Proteins / chemistry*
  • Bone Morphogenetic Proteins / genetics
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Humans
  • Lactates / chemistry*
  • Male
  • Materials Testing
  • Mice
  • Mice, Inbred ICR
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology*
  • Polyethylene Glycols / chemistry*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Transforming Growth Factor beta / administration & dosage*
  • Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta / genetics

Substances

  • BMP2 protein, human
  • Biocompatible Materials
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Delayed-Action Preparations
  • Drug Carriers
  • Lactates
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • polylactic acid-dioxanone-polyethylene glycol block copolymer
  • Polyethylene Glycols