Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold

Biomaterials. 2007 Jun;28(17):2763-71. doi: 10.1016/j.biomaterials.2007.02.023. Epub 2007 Mar 12.


In this study, a heparin-conjugated poly(l-lactic-co-glycolic acid) (HP-PLGA) scaffold was developed for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then used to address the hypothesis that BMP-2 delivered from this scaffold could enhance ectopic bone formation. We found the amount of heparin conjugated to the PLGA scaffolds could be increased up to 3.2-fold by using scaffolds made from star-shaped PLGA, as compared to scaffolds made from linear PLGA, and that the release of BMP-2 from the HP-PLGA scaffold was sustained for at least 14 days in vitro. The BMP-2 released from the HP-PLGA scaffold stimulated an increase in alkaline phosphatase (ALP) activity of osteoblasts for 14 days in vitro, suggesting that the HP-PLGA scaffold delivery system releases BMP-2 in a bioactive form for a prolonged period. By contrast, BMP-2 release from unmodified (no heparin) PLGA scaffolds induced a transient increase in ALP activity for the first 3 days and a decrease thereafter. In vivo bone formation studies showed the BMP-2-loaded HP-PLGA scaffolds induced bone formation to a much greater extent than did either BMP-2-loaded unmodified PLGA scaffolds or unloaded (no BMP-2) HP-PLGA scaffolds, with 9-fold greater bone formation area and 4-fold greater calcium content in the BMP-2-loaded HP-PLGA scaffold group compared to the BMP-2-loaded unmodified PLGA scaffold group. Collectively, these results demonstrate that the HP-PLGA delivery system is capable of potentiating the osteogenic efficacy of BMP-2, and underscore its importance as a possible bone regeneration strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology*
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Cricetulus
  • Female
  • Heparin / chemical synthesis
  • Heparin / chemistry*
  • Humans
  • Hydrolysis
  • Kinetics
  • Lactic Acid / chemical synthesis
  • Lactic Acid / chemistry*
  • Muscle, Skeletal / cytology
  • Osteogenesis / drug effects*
  • Polyglycolic Acid / chemical synthesis
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Porosity
  • Prostheses and Implants
  • Rats
  • Rats, Wistar
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta / administration & dosage*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*


  • BMP2 protein, human
  • Biocompatible Materials
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Polymers
  • Transforming Growth Factor beta
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Heparin
  • Calcium