Tissue Engineering of the Growing Craniofacial Skeleton: Long-term Outcomes of Dipyridamole-coated 3D-printed Bioceramic (3DPBC) Scaffolds on Osteogenesis, Suture Patency and Facial Growth
Maxime M. Wang, BA1, Ricardo Rodriguez Colon, BS2, Gregory D. Kurgansky, BA3, Lukasz Witek, PhD3, Andrea Torroni, MD4, Eduardo D. Rodriguez, MD, DDS4, Bruce N. Cronstein, MD5, Paulo G. Coelho, DDS, PhD3, Roberto L. Flores, MD4.
1New York University School of Medicine, New York, NY, USA, 2Icahn School of Medicine at Mount Sinai, New York, NY, USA, 3New York University College of Dentistry, Department of Biomaterials, New York, NY, USA, 4Hansjörg Wyss Department of Plastic Surgery, New York, NY, USA, 5NYU Langone Health, New York, NY, USA.
PURPOSE: Previous large animal studies of dipyridamole-coated 3D printed bioceramic (3DPBC) scaffolds demonstrate significant bone regeneration compared to unfilled craniofacial defects. This long-term, growing animal model study investigates the effects of 3DPBC scaffolds on: bone regeneration compared to autogenous bone graft, suture patency, and craniofacial growth through the time of facial maturity.
METHODS: Immature rabbits (one month; n=16) underwent unilateral 10mm-diameter craniotomies 2mm from the sagittal and coronal sutures and unilateral 3.5x3.5mm alveolar defect creation 2mm from the maxillary suture. Defects were filled with either 3DPBC scaffolds coated with 1000µM dipyridamole (n=8) or autogenous bone graft (n=8). Rabbits were sacrificed after completion of craniofacial growth (6 months). Micro-computed tomography (µ-CT) images were reconstructed in Amira© to quantify bone regeneration. Morphometric analysis of 3D surface models was used to quantify facial symmetry. Histology was used to qualitatively evaluate bone regeneration and suture patency.
RESULTS: At 6 months, defects repaired with 3DPBC scaffolds regenerated bone comparable to autogenous bone graft and un-operated bone in the calvarium (53.9±3.6% vs. 53.5±3.6% vs. 49.4±2.0%, respectively; ANOVA p=0.95) and significantly greater bone formation was generated in the alveolus (52.9±3.3% vs. 40.7±4.0% vs. 39.3±1.6%; ANOVA p=0.01). Morphometric analysis showed no increased asymmetry of scaffold animals compared to bone graft or un-operated controls (Asymmetry index = 65.5±3.3 vs. 74.9±1.6 vs. 72.32±3.5; ANOVA p = 0.07). Histologically, all sutures remained patent with no ectopic bone growth. CONCLUSION: 3DPBC scaffolds significantly regenerates bone comparable to bone graft without negative effects on craniofacial development or suture patency on long term analysis.
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