Jonathan M Bekisz1, Roberto L Flores2, Lukasz Witek3, Christopher D Lopez4, Christopher M Runyan5, Andrea Torroni6, Bruce N Cronstein7, Paulo G Coelho8. 1. New York University Langone Medical Center, 550 First Avenue, New York, NY 10016, USA. Electronic address: jonathan.bekisz@med.nyu.edu. 2. Hansjörg Wyss Department of Plastic Surgery, New York University Langone Medical Center, 307 East 33rd Street, New York, NY 10016, USA. Electronic address: roberto.flores2@nyumc.org. 3. Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, NY 10010, USA. Electronic address: lw901@nyu.edu. 4. Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, NY 10010, USA; Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA. Electronic address: christopher.lopez2@nyumc.org. 5. Hansjörg Wyss Department of Plastic Surgery, New York University Langone Medical Center, 307 East 33rd Street, New York, NY 10016, USA. Electronic address: crunyan@wakehealth.edu. 6. Department of Oral and Maxillofacial Surgery, New York University Langone Medical Center, 530 First Avneue, New York, NY 10016, USA. Electronic address: andrea.torroni@nyumc.org. 7. Department of Medicine, New York University Langone Medical Center, 550 First Avenue, New York, NY 10016, USA. Electronic address: bruce.cronstein@nyumc.org. 8. Hansjörg Wyss Department of Plastic Surgery, New York University Langone Medical Center, 307 East 33rd Street, New York, NY 10016, USA; Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, NY 10010, USA. Electronic address: pc92@nyu.edu.
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.
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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