3D Printed Beta-TCP Ceramic Bone Replacement Manufactured by Lithography-Based Ceramic Manufacturing (LCM): A Short-Term Rabbit Analysis

BACKGROUND: Despite limitations such as donor-site pain, resorption, and limited size and shape of bone stock, autologous bone grafts are the gold standard for bone replacement (1,2). Although beta-tricalcium phosphate (β-TCP) is an established bone replacement material, wide clinical applications have been limited by lack of bone infiltration within its bulk form. Lithography-based ceramic manufacturing (LCM), a novel form of 3D printing, leverages photopolymerization to create β-TCP structures with higher feature resolution and surface quality than traditional techniques. This fabrication modality allows for increased control of the microarchitecture of the construct creating a porous design that facilitates bony infiltration and enables engineers to manufacture implant sizes and shapes that are not possible with traditional ceramic processing (3). While the technology is promising, limited research is available on LCM fabricated scaffolds in animal models. PURPOSE: This study explores the bone regenerative capacity of LCM fabricated 100% β-TCP scaffolds for the repair of critically-sized mandibular defects using a skeletally mature rabbit model. METHODS: Unilateral critical-sized bony defects (10mm × 10mm, full thickness) were created in mandibular rami of New Zealand White rabbits (N=10). Seven rabbits underwent bony defect repair using LCM scaffolds made of 100% β-TCP and three rabbit defects remained unfilled as negative controls. Animals were euthanized after 8 weeks, and the mandibles were harvested, cleaned and scanned using micro–computed tomography (micro-CT) (μCT 40; SCANCO Medical, Bassersdorf, Switzerland) with 18 μm resolution. Imaging data was processed using Amira Software for three-dimensional (3D) reconstruction and volumetric analysis. Histological analysis was performed using Stevenel blue and van Gieson red picrofuchsin staining. Two-dimensional (2D) histomorphometric quantification was also performed. RESULTS: There was no evidence of scaffold fracture during initial bony defect repair or at necroscopy. No bridging bone was seen in unfilled defects. 3D volumetric analysis revealed bridging bone within LCM β-TCP implant sites yielding 8.62±3.47% in fill of bone. Remaining scaffold volume was 32.95±3.21% of the defect. 2D histologic analysis revealed that mean regenerated bone and remaining scaffold was 14.09±6.7% and 34.14±2.5% of the defect respectively. Bone regeneration and remaining scaffold obtained via 2D histologic analysis were consistent with results from 3D volumetric analysis (p<0.05). Qualitative histological analysis of defect sites repaired with scaffolds revealed areas of vascularized woven and lamellar bone, with no evidence of ectopic bone, excess inflammation, or fracture. CONCLUSION: Bone regeneration in a short-term rabbit model following critical-sized mandibular defect repaired with LCM 100% β –TCP scaffolds demonstrate analogous radiographic and histologic properties as native bone.