Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix

B. H. Woo, B. F. Fink, R. Page, J. A. Schrier, Y. W. Jo, G. Jiang, M. DeLuca, H. C. Vasconez, P. P. DeLuca

Research output: Contribution to journalArticlepeer-review

153 Scopus citations


Purpose. The purpose of this study was to develop a polymeric sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2) and to evaluate local bone growth induced by the sustained release of BMP-2 in an animal model. Methods. BMP-2 was incorporated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres to obtain different release rates. Two sustained and an immediate release implants were produced by suspending the BMP-2 loaded PLGA microspheres in aqueous sodium carboxymethylcellulose (CMC), lyophilizing, and cutting the dried materials to the size of the animal bone defects. The local in vivo release at the implantation site in rat calvarial defects was determined by gamma scintigraphy using radiolabeled BMP-2. The local bone induction in the critical size of rabbit calvarial defects was evaluated six weeks post implantation. Results. The immediate release implant showed about 65% initial drug release within 24 h and the remaining BMP-2 quickly exhausted from the implantation site within 7 days. The sustained release implants, showing 45-55% initial release followed by a prolonged release for 21 days, released a greater amount of BMP-2 at the implantation site and maintained higher serum BMP-2 for the longer period of time compared to the immediate release implant. Significant bone growth was observed in all BMP-2 treated defects while the defects without treatment or with BMP-2-free implant showed minimal bone healing. 75-79% of rabbit calvarial defect area was healed with newly induced bone matrix by the sustained release implants in 6 weeks as compared to 45% recovery from the immediate release implant. Conclusion. The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model.

Original languageEnglish
Pages (from-to)1747-1753
Number of pages7
JournalPharmaceutical Research
Issue number12
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by a grant from the National Institutes of Health (NIH) (1RO1DE14559-01) and the authors thank Genetics Institute, Inc. for kindly supplying the BMP-2 and PLGA microspheres used in this study.


  • BMP-2
  • Bone healing
  • Microsphere
  • PLGA
  • Sustained delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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