Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects

Jonathan M. Bekisz, Roberto L. Flores, Lukasz Witek, Christopher D. Lopez, Christopher M. Runyan, Andrea Torroni, Bruce N. Cronstein, Paulo Coelho

Research output: Contribution to journalArticle

Abstract

Purpose: The objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, bioactive ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model. Materials and methods: Custom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100 μM concentration dipyridamole (DIPY) solution. Sheep (n = 5) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution. Results: No exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (p = 0.013) and 6 weeks (p = 0.046) in vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, p = 0.046 and p = 0.031, respectively). Conclusion: Dipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.

Original languageEnglish (US)
JournalJournal of Cranio-Maxillofacial Surgery
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Dipyridamole
Ceramics
Osteogenesis
Bone Regeneration
Collagen
Tissue Scaffolds
X-Ray Microtomography
Dura Mater
Porosity
Sheep
Inflammation
Bone and Bones

Keywords

  • 3D-printed
  • Calvaria
  • Dipyridamole
  • Osteogenesis
  • Tissue engineering

ASJC Scopus subject areas

  • Surgery
  • Oral Surgery
  • Otorhinolaryngology

Cite this

Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects. / Bekisz, Jonathan M.; Flores, Roberto L.; Witek, Lukasz; Lopez, Christopher D.; Runyan, Christopher M.; Torroni, Andrea; Cronstein, Bruce N.; Coelho, Paulo.

In: Journal of Cranio-Maxillofacial Surgery, 01.01.2017.

Research output: Contribution to journalArticle

Bekisz, Jonathan M. ; Flores, Roberto L. ; Witek, Lukasz ; Lopez, Christopher D. ; Runyan, Christopher M. ; Torroni, Andrea ; Cronstein, Bruce N. ; Coelho, Paulo. / Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects. In: Journal of Cranio-Maxillofacial Surgery. 2017.
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AU - Lopez, Christopher D.

AU - Runyan, Christopher M.

AU - Torroni, Andrea

AU - Cronstein, Bruce N.

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AB - Purpose: The objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, bioactive ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model. Materials and methods: Custom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100 μM concentration dipyridamole (DIPY) solution. Sheep (n = 5) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution. Results: No exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (p = 0.013) and 6 weeks (p = 0.046) in vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, p = 0.046 and p = 0.031, respectively). Conclusion: Dipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.

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