Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing |
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Authors: | Jay A Schrier Betsy F Fink Janet B Rodgers Henry C Vasconez Patrick P DeLuca |
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Institution: | (1) Faculty of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 40536 Lexington, KY;(2) Biotechnology Facility, Magellan Laboratories, Inc., 92126 San Diego, CA;(3) Division of Plastic Surgery, Department of Surgery, College of Medicine, University of Kentucky, 40536 Lexington, KY;(4) Division of Laboratory Animal Resources. College of Research and Graduate Studies, University of Kentucky, 40536 Lexington, KY |
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Abstract: | The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic
protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than
would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary
to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling.
Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them
in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded
microspheres by lyophilization matrices for implantation were prepared by lyophilizing a suspension of the microspheres in
2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres.
A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect
well allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology.
In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days. With the unembedded microspheres
releasing faster than those embedded in CMC In vivo. the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded
PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2 PLGA microspheres
in CMC was an effective implantable protein-delivery system for the use in bone repair.
Published: October 7. 2001. |
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Keywords: | bone morphogenetic protein-2 PLGA microspheres controlled delivery protein delivery in vitro in vivo bone repair |
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