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Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.


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 ?-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 ?M 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.

SUBMITTER: Lopez CD 

PROVIDER: S-EPMC6620113 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.

Lopez Christopher D CD   Diaz-Siso J Rodrigo JR   Witek Lukasz L   Bekisz Jonathan M JM   Gil Luiz F LF   Cronstein Bruce N BN   Flores Roberto L RL   Torroni Andrea A   Rodriguez Eduardo D ED   Coelho Paulo G PG  

Plastic and reconstructive surgery 20190501 5


<h4>Background</h4>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.<h4>Methods</h4>Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15).  ...[more]

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