Abstract: 3D-Printed Bioactive Ceramic Scaffolds Demonstrate Intrinsic Osteogenic Properties in an Undisturbed Osseous Environment

Abstract

INTRODUCTION: The osteogenicity of 3D-printed bioactive ceramic (3DBC) scaffolds has been demonstrated in several translational models. Scaffolds can be designed to fit and fill defect sites while directing osseosynthesis by utilizing the micro-environmental cues of violated bone primed for healing. However, preoperative access to large segments of accessory bone replacement could be of significant benefit, particularly in settings of planned oncologic resection or congenital correction. Despite this, the osseoconductivity of biomaterials synthesized with 3D-printed geometric design to optimize bone growth has not been explored in an intact bone model. This study used a sheep model to evaluate the innate ability of 3DBC scaffolds to induce bone growth supplementary to the undisturbed calvarium. METHODS: Cylindrical 3DBC scaffolds, measuring ~5-mm in diameter and ~1.5-mm in height, were composed of 100% β-tricalcium phosphate and designed with an inner lattice network and solid outer wall. Dorset-Finn sheep (n=5) underwent surgical placement of four 3DBC scaffolds subperiosteally on top of the calvarial bone, which were stabilized by periosteal closure. Two scaffolds were placed on each side of the calvarium, with the right-left distinction corresponding to the treatment period length (3- vs. 6-weeks). Samples were evaluated through histologic quantification of bone, scaffold, and soft tissue as a function of time in vivo. For between-group comparisons, statistical analysis was conducted using a Student’s t-test with 95% confidence intervals and significance was set at an α=0.05. RESULTS: On histologic analysis, there was no evidence of inflammation around the scaffold site. Gross examination revealed a trend of bone growth from the calvarium into the interior lattice network and up the outer walls of the scaffold in an inferior-superior directionality. At the 6-week timepoint, samples demonstrated a significantly greater mean of available space occupied by bone (23.33 ± 3.4% vs 14.35 ± 3.72%; p<0.01). When bone and scaffold were considered together, there was no significant difference in mean space occupancy (6-Week: 56.86 ± 5.88%, 3-Week: 63.27 ± 12.98%; p=0.43), suggesting a stable rate of scaffold degradation/osseous remodeling over time. CONCLUSION: 3DBC scaffolds composed of β-TCP are capable of inducing bone growth in an undisturbed osseous environment. This osteogenic influence is continually exerted over time, necessitating longer-term follow-up to determine the temporality of the bone-forming capacity of this tissue engineering construct. *Christopher D Lopez and Jonathan M Bekisz contributed equally to this work.

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