Leveraging 3d Printing To Transform The Degradation Profile Of β-tricalcium Phosphatebone Replacement
Chen Shen, BS1, Maxime M. Wang, BA1, Lukasz Witek, MSci, PhD2, Bruce N. Cronstein, MD3, Andrea Torroni, MD, PhD1, Daniel J. Ceradini, MD1, Roberto L. Flores, MD1, Paulo G. Coelho, DDS, PhD2.
1Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA, 2NYU College of Dentistry, New York, NY, USA, 3NYU School of Medicine, New York, NY, USA.
PURPOSE: Craniosynostosis and cleft lip and palate are the two most common conditions treated by craniofacial surgeons. Because of the need for bony reconstruction and limited bone stock in pediatric patients, alternatives to autologous bone grafting to fill bony defects are required. β-tricalcium phosphate (β-TCP), the most common synthetic bone replacement product, is frequently used in craniofacial reconstruction. Although solid β-TCP can be absorbed over time, the slow degradation rate (1-3%/year) predisposes this product to exposure, infection, and fracture, limiting its use in the growing face where implants are required to grow and remodel with the patient. Our tissue engineering laboratory has successfully leveraged 3D printers to manufacture 3D-printed bioactive ceramic (3DPBC) scaffolds composed of β-TCP in an architecture which optimizes the needs of rigidity with efficient vascular ingrowth, osteogenesis, and degradation kinetics. The latter qualities are further optimized when the osteogenic agent dipyridamole (DIPY) is used. This long-term animal study of immature rabbits through the time of facial maturity reports on the new degradation kinetics profile achievable through this novel manufacturing and tissue engineering protocol.
METHODS: Twenty-two one-month-old (immature) New Zealand White rabbits underwent creation of unilateral 10 mm calvarial defects with ipsilateral 3.5×3.5 mm alveolar defects. Each defect was repaired with 3DPBC scaffolds composed of 100% β-TCP and coated with 1,000 µM DIPY. Rabbits were sacrificed at 8 weeks (n=6), 6 months (n=8), and 18 months (n=8). Bone regeneration and scaffold degradation were calculated using micro-CT images and analyzed in Amira software. Cranial and maxillary suture patency and bone growth were qualitatively analyzed using histologic analysis.
RESULTS: Results are reported as a percentage of volumetric space occupied by either scaffold or bone. When comparing time points 8 weeks, 6 months, and 18 month, scaffolds showed significantly decreased in vivo defect occupancy in calvaria (23.6±3.6%, 15.2±1.7%, and 5.1±3.4%; p < 0.001) and in alveoli (21.5±3.9%, 6.7±2.7%, and 0.1±0.2%; p < 0.001), with annual degradation rates 55.9% and 94.2%, respectively. Between 8 weeks and 18 months, significantly more bone regenerated in calvarial defects (25.8±6.3% vs. 55.7±10.3%, p < 0.001) and no difference was found in alveolar defects (28.4±6.8% vs. 32.4±8.0%, p = 0.33). Histology and mechanical testing revealed vascularized and organized bone without suture fusion.
CONCLUSION: The degradation kinetics of β-TCP can be altered through 3D printing and addition of an osteogenic agent. Our study demonstrates an acceleration of β-TCP degradation from 1-3% a year to 55-95% a year. Absorbed β-TCP is replaced by vascularized, organized bone, with histologic and mechanical properties similar to native bone and without damage noted to the growing suture. This additive manufacturing and tissue engineering protocol has implication to future reconstruction of the craniofacial skeleton, especially as a safe and efficacious method in pediatric bone tissue engineering.
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