Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone. Issue 5 (May 2019)

• Record Type: Journal Article
• Authors: Lopez, Christopher D.; Diaz-Siso, J. Rodrigo; Witek, Lukasz; Bekisz, Jonathan M.; Gil, Luiz F.; Cronstein, Bruce N.; Flores, Roberto L.; Torroni, Andrea; Rodriguez, Eduardo D.; Coelho, Paulo G.
• Is Part Of: Plastic and reconstructive surgery. Volume 143:Issue 5(2019:May)
• Publication Date: 2019-05
• Subjects: Surgery, Plastic -- Periodicals; 617.95205
• DOI: 10.1097/PRS.0000000000005531
• Languages: English
• ISSNs: 0032-1052

Abstract

Abstract : Background: Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. Methods: Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits ( n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro–computed tomography/advanced reconstruction software. Micro–computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. Results: Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group ( p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. Conclusion: Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment. Abstract : Supplemental Digital Content is available in the text.