Bone Tissue Engineering in the Growing Calvarium Using Dipyridamole-Coated 3D Printed Bioceramic Scaffolds: Construct Optimization and Effects to Cranial Suture Patency

BACKGROUND/PURPOSE:3D-printed bioceramic (3DBC) scaffolds composed of beta-tricalcium phosphate (β-TCP) delivering the osteogenic agent dipyridamole (DIPY) can heal critically-sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, we implanted 3DBC/DIPY scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and DIPY concentration. Potential adverse effects on the growing suture were also evaluated. METHOD/DESCRIPTION:Bilateral calvarial defects (10 mm) were created in 5-week-old (~1.1 kg) New Zealand White rabbits (n = 16 analyzed). 3DBC scaffolds were constructed in quadrant form composed of varying pore dimensions (220μm, 330μm, 500μm). Each scaffold was collagen coated and soaked in varying concentrations of DIPY (100μM, 1000μM, 10,000μM). Controls comprised empty defects. Animals were euthanized 8-weeks post-operatively. Calvaria were analyzed using micro-computed tomography (microCT), 3D reconstruction, and non-decalcified histologic sectioning. RESULTS:Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p=0.02). Large scaffold pores, 500μm, coated in 1,000μM DIPY yielded the most bone growth and lowest degree of scaffold presence within defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. MicroCT and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all DIPY concentrations. CONCLUSION:We present an effective pediatric bone tissue engineering scaffold design and dipyridamole concentration which is effective in augmentation of calvarial bone generation while preserving cranial suture patency.