Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Biopatterned Recombinant Human Bone Morphogenetic Protein 2 Does Not Induce Pansynostosis or Growth Restriction in the Immature Craniofacial Skeleton
Sameer Shakir, BS1, Osama Basri, DMD1, James J. Cray, PhD2, Sanjay Naran, MD1, Darren M. Smith, MD3, Zoe M. MacIsaac, MD1, Evan B. Katzel, MD1, Weinberg M. Seth, PhD1, Mark P. Mooney, PhD1, Joseph E. Losee, MD1, Cooper M. Greg, PhD1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2Medical University of South Carolina, Charleston, SC, USA, 3Hospital for Sick Children, Toronto, ON, Canada.

PURPOSE:
When other therapeutic options have failed, rhBMP-2 may help to heal problematic calvarial defects. While rhBMP-2 remains a potent osteoinductive agent, current off-label applications normally far supersede physiologic concentrations and may contribute to previously reported side effects including ectopic bone formation, inflammation, and cancer. Furthermore, the efficacy of rhBMP-2 therapy in the skeletally immature pediatric patient with a nonhealing calvarial defect remains unknown. The study aimed to compare the effects of rhBMP-2 dose on cranial growth in a juvenile New Zealand White rabbit strip suturectomy model with the hypothesis that higher dose rhBMP-2 negatively affects cranial growth.
METHODS:
Twenty juvenile New Zealand White rabbits underwent bicoronal strip suturectomies treated with 0.4-mg/mL rhBMP-2/absorbable collagen sponge (n=7), 100-ug/mL biopatterned rhBMP-2/acellular dermal matrix (n=6), or left empty (n=7). Amalgam markers were placed at suture confluences to radiographically track suture separation and cranial growth at 10, 25, and 42 days of age. Means and standard deviations for craniofacial growth variables were calculated and compared using two-way ANOVA statistical analysis. Cranial sutures were qualitatively assessed using micro-computed tomographic (uCT) scanning at 42 days postoperatively.
RESULTS:
Treatment with 0.4mg/mL rhBMP-2 resulted in significant growth changes and fusion of the coronal sutures bilaterally, anterior sagittal suture, and frontonasal suture by cephalometric analyses at 42 days postoperatively (p<0.05). Growth changes appeared greatest in the nasal region and less in the bicoronal and anterior sagittal regions. No significant differences in cranial growth were noted with use of 100-ug/mL biopatterned rhBMP-2 when compared to the empty defect group. Qualitative uCT analysis revealed comparable bony defect healing between rhBMP-2 groups. Application of high-dose, 0.4mg/mL rhBMP-2 resulted in pansynostosis upon uCT analysis, further verifying cranial growth restriction. Low-dose, 100-ug/mL biopatterned rhBMP-2 consistently regenerated bone within the surgical defect margin without evidence of extra-sutural invasion.
CONCLUSION:
Use of rhBMP-2 results in unwanted craniofacial changes in a dose-dependent manner. Local effects of high dose rhBMP-2 include pansynostosis and growth restriction that may limit its potential translation into the clinical setting. However, low dose biopatterned rhBMP-2 regenerates bone within a target defect without causing these undesirable side effects. This low-dose, spatially controlled methodology of growth factor delivery may improve the clinical efficacy of current off-label use of rhBMP-2 in the immature craniofacial skeleton.


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