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Release Kinetics of Polymer-Bound Bone Morphogenetic Protein-2 and Its Effects on the Osteogenic Expression of MC3T3-E1 Osteoprecursor Cells

Gharibjanian, Nareg A. M.S.; Chua, Walter C. M.D.; Dhar, Sanjay Ph.D.; Scholz, Thomas M.D.; Shibuya, Terry Y. M.D.; Evans, Gregory R. D. M.D.; Calvert, Jay W. M.D.

Plastic and Reconstructive Surgery: April 2009 - Volume 123 - Issue 4 - p 1169-1177
doi: 10.1097/PRS.0b013e31819f2987
Experimental: Original Articles

Background: In an effort to augment scaffold performance, additives such as growth factors are under investigation for their ability to optimize the “osteopotential” of synthetic polymer scaffolds. In parallel research, bone morphogenetic protein-2 (BMP-2), a growth factor that initiates bone formation, has been locally delivered to augment fracture healing and spinal fusion. The authors hypothesize that BMP-2 can be covalently bound to a polymer substrate, increasing its concentration and bioavailability over longer periods, thus improving the efficacy of the growth factor and subsequently the bony matrix production. It would remain bound longer when compared with published controls. This prolonged binding would then increase the bioavailability of the growth factor and thus increase bony matrix production over a longer interval.

Methods: Mouse preosteoblast MC3T3-E1 cells were cultured on poly(lactic-co-glycolic acid) and polycaprolactone polymer disks covalently bound with BMP-2 to assess the progression and quality of osteogenesis. Covalent binding of BMP-2 to each polymer was visualized by immunohistochemical analysis of polymer-coated microscope slides. The quantity of covalently bound BMP-2 was determined using enzyme-linked immunosorbent assay.

Results: Polymerase chain reaction results showed elevated expression levels for alkaline phosphatase and osteocalcin genes. BMP-2 was released from polycaprolactone over 2 weeks, with 86 percent remaining covalently bound, in contrast to 93 percent retained by poly(lactic-co-glycolic acid).

Conclusions: BMP-2, proven to alter polymer osteogenicity, remained bound to poly(lactic-co-glycolic acid), which may render poly(lactic-co-glycolic acid) an ideal choice as a polymer for scaffold-based bone tissue engineering using growth factor delivery.

Orange, Calif.

From the Aesthetic and Plastic Surgery Institute and the Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine.

Received for publication May 22, 2008; accepted October 6, 2008.

Presented at the 49th Annual Meeting of the Plastic Surgery Research Council, in Ann Arbor, Michigan, June 9 through 12, 2004.

Disclosure: None of the authors has a financial interest or commercial association that might pose or create a conflict of interest with the information presented in this article.

Jay W. Calvert, M.D., Department of Surgery, Veterans Affairs Hospital, 5901 East 7th Street, Long Beach, Calif. 90822,

©2009American Society of Plastic Surgeons