Design, fabrication, and characterization of 3D printed ceramic scaffolds for bone regeneration
Date
2024
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Abstract
Synthetic bone tissue scaffolds are a promising alternative to current clinical techniques for treating critically large bone defects. Scaffolds provide a three-dimensional (3D) environment that mimics the properties of bone to accelerate bone regeneration. Optimal scaffolds should match the mechanical properties of the implantation site, feature a highly porous network of interconnected channels to facilitate mass transport, and exhibit surface properties for the attachment, proliferation, and differentiation of bone cell lineages. 3D printing has enabled the manufacture of complex scaffold topologies that meet these requirements in a variety of biomaterials which has led to rapidly expanding research. Structural innovations such as triply periodic minimal surfaces (TPMS) are enabling the production of scaffolds that are stiffer and stronger than traditional rectilinear topologies. TPMS are proving to be ideal candidates for bone tissue engineering (BTE) due to their relatively high mechanical energy absorption and robustness, interconnected internal porous structure, scalable unit cell topology, and smooth internal surfaces with relatively high surface area per volume. Among the material options, calcium phosphate-based ceramics, such as hydroxyapatite and tricalcium phosphate, are popular for BTE due to their high levels of bioactivity (osteoconductivity, osteoinductivity and osteointegration), compositional similarities to human bone mineral, non-immunogenicity, tunable degradation rates, and promising drug delivery capabilities. Despite the potential for TPMS ceramic scaffolds in BTE, few studies have explored beyond the popular Gyroid topology. Of the many TPMS options, the Fischer Koch S (FKS) has been simulated to be stronger, be more isotropic, have higher surface area, and absorb more energy than Gyroid at high porosities. In this report, we present a method for photocasting any TPMS in hydroxyapatite which is used to 3D print the first FKS ceramic scaffold. Results indicated that the resolution and accuracy of the process is suitable for BTE, and the custom software for producing the scaffolds was made available to the open-source community. Then, FKS and Gyroid scaffolds were designed to match the properties of trabecular bone using this method for use in critical bone defect repair. The scaffolds were printed and characterized using compressive and flow-based testing to reveal that, while both designs could mimic the low end of natural bone performance, the FKS were 32% stronger and only 11% less permeable than Gyroid. These findings emphasized the need for further characterization of these scaffolds beyond mechanical analysis and into studies of cell growth. To accomplish this, a custom multi-channel perfusion bioreactor was designed to culture cells on these scaffolds to investigate differences in cell behavior with higher efficiency than current designs. The design, capable of culturing many samples simultaneously, was validated using computational fluid dynamics and cell growth assays to demonstrate osteogenic effects and repeatability. In this work, novel TPMS scaffolds were fabricated from hydroxyapatite with sufficient accuracy and quality for large defects, testing of these scaffolds matched trabecular bone performance and suggested that FKS may be superior to Gyroid, and lastly, a four-channel bioreactor system was designed and validated to enable researchers to further characterize scaffolds for BTE.
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Subject
bioreactor
Gyroid
scaffolds
Fischer Koch S
3D printing
perfusion