Three-Dimensionally-Printed Bioactive Ceramic Scaffolds Containing Interconnected Porous Architecture: Is Dura-mediated Osteoinduction Required for Calvarial Bone Replacement?

PURPOSE: Three-dimensional printed (3DP) bioceramic scaffolds composed of beta-tricalcium phosphate (β-TCP), which possess an interconnected porous architecture, have previously demonstrated the ability to promote bone regeneration across critically-sized calvarial defects. Cranioplasty procedures, however, are often performed when the dura mater is scarred, compromised, or absent, reducing the potential for dura-mediated osteoinduction. This study evaluates whether the interconnected porosity of 3DP β-TCP scaffolds alone is sufficient to support bone regeneration across critically-sized calvarial defects in the absence of dura-mediated osteoinduction. METHODS: Critical-sized, 11mm unilateral calvarial defects were created in skeletally mature rabbits (n=11). Following defect creation, each rabbit received one of two scaffold designs in the defect: (i) a 3DP β-TCP scaffold with a solid, nonporous cap on the inferior surface, preventing direct contact between the scaffold’s porous structure and the dura mater, or (ii) a scaffold with a fully porous inferior surface, allowing direct interaction with the dura and enabling dura-mediated osteoinduction. The animals were euthanized 8 weeks postoperatively, and calvarial samples were harvested for analysis. Qualitative morphometric and quantitative volumetric analysis was performed using histology and micro-computed tomography (μCT) imaging, respectively, to evaluate bone, soft tissue, and scaffold. Data was analyzed using generalized linear mixed model, with fixed factor variable of scaffold design (closed versus open), reported as mean and 95% confidence interval. RESULTS: Volumetric analysis revealed no significant differences between scaffold designs regarding bone volume (open: 9.3% ± 4.5 vs. closed: 10.2% ± 4.5; p=0.71), soft tissue volume (open: 58.5% ± 7.0 vs. closed: 52.5% ± 2.0; p=0.07), or scaffold volume (open: 32.3% ± 3.4 vs. closed 37.3% ± 4.3; p=0.92). Both scaffold designs demonstrated successful bridging bone across the calvarial defects, irrespective of the scaffold design. Qualitative histological analysis revealed vascularized bone within the scaffold with presence of Haversian canals. CONCLUSION: This pilot study demonstrated that 3DP β-TCP scaffolds with an interconnected porous architecture facilitate bone regeneration across critically-sized calvarial defects, even without dura-mediated osteoinduction. Both scaffold designs, whether a porous or solid cap, resulted in analogous levels of bone formation, indicating that osteoconduction through the scaffold’s interconnected pores is a sufficient mechanism to support bone regeneration. These findings suggest that 3DP bioceramic scaffolds have the potential to serve as an effective alternative to traditional bone grafts in cranioplasty procedures, particularly when the dura is absent or compromised. The results from this pilot study could inform future designs of tissue-engineered scaffolds for cranial reconstruction, offering a potential solution for patients with scarred or missing dura.