Regeneration of a Pediatric Alveolar Cleft Model Using Three-Dimensionally Printed Bioceramic Scaffolds and Osteogenic Agents: Comparison of Dipyridamole and rhBMP-2

Christopher D. Lopez, Paulo G. Coelho, Lukasz Witek, Andrea Torroni, Michael I. Greenberg, Dean L. Cuadrado, Audrey M. Guarino, Jonathan M. Bekisz, Bruce N. Cronstein, Roberto L. Flores

Research output: Contribution to journalArticlepeer-review


Background: Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds. Methods: Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 μm of dipyridamole (n = 6), 10,000 μm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test. Results: Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-μm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-μm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 μm versus 10,000 μm dipyridamole; p = 0.104), and rhBMP-2–coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 μm dipyridamole, and p = 0.938 versus 10,000 μm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone. Conclusion: Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects. (Plast. Reconstr. Surg. 144: 358, 2019.)

Original languageEnglish (US)
Pages (from-to)358-370
Number of pages13
JournalPlastic and reconstructive surgery
Issue number2
StatePublished - Aug 1 2019


  • Alveolar Process/drug effects
  • Animals
  • Bone Density Conservation Agents/administration & dosage
  • Bone Morphogenetic Protein 2/administration & dosage
  • Bone Regeneration/drug effects
  • Bone Transplantation/methods
  • Dipyridamole/administration & dosage
  • Disease Models, Animal
  • Microscopy, Electron, Scanning
  • Models, Animal
  • Osteogenesis/drug effects
  • Printing, Three-Dimensional
  • Rabbits
  • Recombinant Proteins/administration & dosage
  • Tissue Scaffolds
  • Transforming Growth Factor beta/administration & dosage
  • X-Ray Microtomography

ASJC Scopus subject areas

  • Surgery


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