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Augmenting Neovascularization Accelerates Distraction Osteogenesis

Davidson, Edward H. M.A., M.B.B.S.; Sultan, Steven M. B.A.; Butala, Parag M.D.; Tutela, John Paul M.D.; Canizares, Orlando M.D.; Wagner, I. Janelle M.D.; Knobel, Denis M.D.; Saadeh, Pierre B. M.D.; Warren, Stephen M. M.D.

Plastic and Reconstructive Surgery: August 2011 - Volume 128 - Issue 2 - p 406-414
doi: 10.1097/PRS.0b013e31821e6e2e
Experimental: Original Articles

Background: Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction.

Methods: Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.25 mm twice daily), and 21-day consolidation periods. From the beginning of the consolidation period, animals received daily injections of either AMD3100 (bone marrow progenitor cell mobilizing agent) or sterile saline. Animals were euthanized on postoperative day 31; mandibles were harvested; and bone regeneration was assessed using micro–computed tomography, immunohistochemistry, bone morphogenetic protein-2 enzyme-linked immunosorbent assay, and mechanical testing.

Results: Immunohistochemistry demonstrated that AMD3100 treatment increased vascular density and bone formation. Micro–computed tomography and dual-emission x-ray absorptiometry demonstrated that AMD3100-treated animals had improved bone generation compared with sham-treated controls. Greater force was required on three-point testing to break AMD3100-treated bone. Bone morphogenetic protein-2 expression was up-regulated with AMD3100. Interestingly, the nondistracted contralateral hemimandibles treated with AMD3100 were also stronger than sham-treated counterparts.

Conclusions: Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow.

New York, N.Y.

From the Institute of Reconstructive Plastic Surgery, New York University Langone Medical Center.

Received for publication August 7, 2010; accepted February 7, 2011.

Stephen M. Warren, M.D., Institute of Reconstructive Plastic Surgery, New York University Medical Center, 560 First Avenue, TCH-169, New York, N.Y. 10017,

Disclosure: The authors receive Plerixafor for experimental use through a nonfinancial relationship with Genzyme. They have no financial interests to declare.

©2011American Society of Plastic Surgeons