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

Christopher D. Lopez, J. Rodrigo Diaz-Siso, Lukasz Witek, Jonathan M. Bekisz, Luiz F. Gil, Bruce N. Cronstein, Roberto L. Flores, Andrea Torroni, Eduardo D. Rodriguez, Paulo Coelho

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1408-1419
Number of pages12
JournalPlastic and reconstructive surgery
Volume143
Issue number5
DOIs
StatePublished - May 1 2019

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Dipyridamole
Ceramics
Bone and Bones
Collagen
Bone Development
Adenosine A2 Receptor Agonists
Control Groups
Standard of Care
Osteogenesis
Linear Models
Histology
Software
Tomography
Confidence Intervals
Rabbits
Transplants

ASJC Scopus subject areas

  • Surgery

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

In: Plastic and reconstructive surgery, Vol. 143, No. 5, 01.05.2019, p. 1408-1419.

Research output: Contribution to journalArticle

Lopez, CD, Diaz-Siso, JR, Witek, L, Bekisz, JM, Gil, LF, Cronstein, BN, Flores, RL, Torroni, A, Rodriguez, ED & Coelho, P 2019, 'Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone', Plastic and reconstructive surgery, vol. 143, no. 5, pp. 1408-1419. https://doi.org/10.1097/PRS.0000000000005531
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. / Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone. In: Plastic and reconstructive surgery. 2019 ; Vol. 143, No. 5. pp. 1408-1419.
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AU - Witek, Lukasz

AU - Bekisz, Jonathan M.

AU - Gil, Luiz F.

AU - Cronstein, Bruce N.

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N2 - 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.

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