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“Regeneration of a Pediatric Alveolar Cleft Model using 3D Printed Bioceramic Scaffolds and Osteogenic Agents

Comparison of Dipyridamole and rhBMP-2.”

Lopez, Christopher D.1,2,3; Coelho, Paulo G.1,2; Witek, Lukasz2; Torroni, Andrea1; Greenberg, Michael I.2; Cuadrado, Dean L.2; Guarino, Audrey M.2; Bekisz, Jonathan M.1; Cronstein, Bruce N.4; Flores, Roberto L.1

Plastic and Reconstructive Surgery: May 7, 2019 - Volume PRS Online First - Issue - p
doi: 10.1097/PRS.0000000000005840
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Purpose: Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although rhBMP-2 is under investigation for alveolar cleft repair, safety concerns remain (e.g. growing suture pathology). Dipyridamole (DIPY) is an adenosine receptor indirect agonist with known osteogenic potential. This study compared DIPY to rhBMP-2 at alveolar cleft defects delivered via 3D-printed bioceramic (3DBC) scaffolds.

Methods: Skeletally immature New Zealand White rabbits underwent unilateral, 3.5mm x3.5mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with 3DBC scaffolds coated with 1000μm-DIPY (n=6), 10,000μm-DIPY (n=7), and 0.2 mg/mL-rhBMP-2 (n=5). At t=8 weeks, new bone was quantified using Amira 6.1 software. Non-decalcified histology was performed, and new bone was mechanically evaluated. Statistical analysis was performed using a generalized linear mixed model and Wilcoxon rank sum test.

Results: Negative controls did not heal while new bone formation bridged all 3DBC treatment groups. 1,000μm-DIPY scaffolds regenerated 28.03±7.38%, 10,000μm-DIPY scaffolds regenerated 36.18±6.83% (p=0.104 1,000μm vs. 10,000μm DIPY), and rhBMP-2 coated scaffolds regenerated 37.17±16.69% bone (p=0.124 vs. 1,000μm-DIPY and p=0.938 vs. 10,000μm-DIPY). On histology/electron microscopy, no changes in suture biology were evident for DIPY, while 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 DIPY or rhBMP-2 when compared to native bone.

Conclusion: Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.

1. Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY

2. Department of Biomaterials & Biomimetics at NYU College of Dentistry, New York NY

3. Icahn School of Medicine at Mount Sinai, New York, NY

4. Division of Translational Medicine, Department of Medicine, NYU Langone Health, New York, NY

This work will be presented in abstract form at Plastic Surgery The Meeting 2018.

Financial Disclosure Statement: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Funding: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development [award R21HD090664] and National Institute of Arthritis and Musculoskeletal and Skin Diseases [award R01AR068593 and award supplement R01AR068593-02S1].

Corresponding author: Christopher D. Lopez, BA, Research Fellow, Hansjörg Wyss Department of Plastic Surgery, NYU School of Medicine & Department of Biomaterials, NYU College of Dentistry, MD Candidate, Icahn School of Medicine at Mount Sinai

©2019American Society of Plastic Surgeons