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Dipyridamole-Containing 3D-Printed Bioactive Ceramic Scaffolds for the Treatment of Calvarial Defects: An Experimental Study in Sheep
Jonathan M. Bekisz, BA1, Roberto L. Flores, MD1, Lukasz Witek, MSci, PhD2, Christopher D. Lopez, BA3, Christopher Runyan, MD, PhD1, Andrea Torroni, MD1, Bruce N. Cronstein, MD1, Paulo G. Coelho, DDS, PhD2.
1New York University School of Medicine, New York, NY, USA, 2New York University School of Dentistry, New York, NY, USA, 3Icahn School of Medicine at Mount Sinai & New York University School of Medicine, New York, NY, USA.

PURPOSE: Previous studies have demonstrated the efficacy of 3D-printed bioactive ceramic (3DBC) scaffolds in the restoration of long bone defects. The objective of this study is to test the efficacy of the osteogenic agent dipyridamole on 3DBC scaffold-mediated healing of calvarial defects using a sheep model.
METHODS: Custom 3DBC scaffolds were either coated with collagen (control) or coated with collagen and immersed in 100 µM dipyridamole (DIPY). Sheep (n=5) were subjected to 4 trephine-induced (12 mm diameter) calvarial defects with immediate scaffold placement via two separate operations: anteriorly (control) and posteriorly (DIPY) on the right (3 weeks healing) and left (6 weeks healing) sides of the calvarium. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification as a function of time in vivo. Statistical analysis was performed by a mixed model and significance was defined by p<0.05.
RESULTS: Histologic evaluation demonstrated no signs of inflammation within the defects. Significantly higher percentage of bone formation (p=0.02) was observed for the DIPY-containing scaffolds. A significant increase in bone percentage was observed from 3 to 6 weeks in vivo irrespective of scaffold group (p<0.01). Differences between groups were more pronounced at 6 weeks in vivo (~90% more for DIPY). No exuberant or ectopic bone formation was observed in either experimental group.
CONCLUSION: Defects treated with dipyridamole-containing 3DBC scaffolds demonstrated significantly improved bone generation without histologic evidence of inflammation or ectopic bone formation.


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