Bone Tissue Engineering of the Pediatric Calvarium and Alveolus using Dipyridamole-coated 3D-Printed Bioactive Ceramic Scaffolds
Samantha G. Maliha, BA1, Christopher D. Lopez, BA2, Madison E. Cox, HSD3, Lukasz Witek, MSci, PhD4, Fady G. Gendy, HSD5, Andrea Torroni, MD, PhD6, Bruce N. Cronstein, MD7, Roberto L. Flores, MD6, Paulo G. Coelho, DDS, PhD4.
1New York University School of Medicine, New York, NY, USA, 2Icahn School of Medicine at Mount Sinai, New York, NY, USA, 3Columbia University, New York, NY, USA, 4New York University College of Dentistry, Department of Biomaterials, New York, NY, USA, 5Baruch College, New York, NY, USA, 6New York University Langone Health, Hansjörg Wyss Department of Plastic Surgery, New York, NY, USA, 7New York University Langone Health, Department of Translational Medicine, New York, NY, USA.
PURPOSE: The purpose of this study is to apply 3D-printed bioactive ceramic (3DPBC) scaffolds composed of beta-tricalcium phosphate (β-TCP) and coated in the osteogenic agent dipyridamole (DIPY) in a growing craniofacial animal model and: 1) quantify osteogenesis 2) assess suture patency. In our calvaria models, we further sought to identify the best scaffold design and dipyridamole concentration.
METHODS: In calvaria models, bilateral defects (10 mm) were created in 5-week-old New Zealand White rabbits (n = 16) 2mm posterior and lateral to the coronal and sagittal sutures, respectively. 3DPBC scaffolds were constructed in quadrant form composed of varying pore dimensions (220μm, 330μm, 500μm). Each scaffold was collagen coated and soaked in three concentrations of DIPY (100μM, 1,000μM, and 10,000μM) (n=8 each group). In cleft models, immature New Zealand White rabbits (n = 22) underwent unilateral 3.5mm by 3.5mm alveolar cleft defect injury. Defects were filled with 3DPBC scaffolds composed of 330μm pore size and soaked in varying concentrations of DIPY (4 in 100μM, 6 in 1,000μM, and 8 in 10,000μM). In both models, controls comprised of empty defects. All animals were euthanized 8-weeks post-operatively. Both models were analyzed using micro-computed tomography and histologic analysis. Mixed model analyses were conducted to compare pore size in the calvaria group and dosage effects on bone growth in both groups.
RESULTS: Scaffolds induced vascularized bone formation across the calvarial and cleft defects whereas control bone growth was restricted to margins in both. In calvaria models, dipyridamole concentration was analyzed independently of pore size to reveal that 1000μM resulted in the greatest degree of bone formation (p<0.05). Despite robust bone formation across all pores, there was no evidence for one size being significantly better than the other. In cleft models, 10,000μM resulted in greatest degree of bone formation (p<0.05). There was no exuberant bone formation across all concentrations of dipryridamole, and sutures remained patent in all experimental groups.
CONCLUSION: We present an optimized bone tissue engineering scaffold design and dipyridamole concentration for bone generation within growing pediatric calvarial and cleft defects which preserves cranial suture patency and does not form ectopic bone.
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