3D Printing of Nano Biphasic Calcium Phosphate Bioceramic for Fabricating Bone Tissue Engineering Scaffolds

Bone tissue engineering is now regarded as an effective treatment for bone tissue loss or damage. Porous scaffolds, as an essential component of scaffold-based tissue engineering, act as a temporary structural support for cell attachment, proliferation and differentiation and for extracellular matrix secreted by cells and play a crucial role for bone tissue neo-formation and integration. Biphasic calcium phosphate (BCP) is a promising bioceramic for bone tissue engineering scaffolds owing to its advantages as a hybrid of hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP), including good biocompatibility, osteoconductivity, possible osteoinductivity and controllable biodegradation rate. With its impressive advances in recent years, 3D printing provides a new platform for fabricating bone tissue engineering scaffolds with desired porous structures and controlled pore morphologies. Among current 3D printing technologies, digital light processing (DLP) is one of the promising approaches to construct ceramic parts with high resolution and accuracy, as well as desirable mechanical properties. For DLP, nano-sized ceramic particles are beneficial for obtaining the desired properties for the final ceramic products. However, achieving optimal conditions for the preparation and processing of ceramic nanoparticle-based slurries in DLP is still a significant challenge. In this work, stable and well-dispersed slurries composed of nano-sized BCP powders were prepared and porous BCP bioceramic scaffolds with good bioactivity were accurately manufactured via DLP 3D printing and optimized sintering. First, four types of dispersants were assessed for powder surface modification of nano-sized BCP powders, aiming to select one best dispersant with the optimal concentration which could decrease nanoparticle agglomeration and achieve high solid-loading for BCP slurry. Second, the effects of photoinitiator concentration and solid loading on the rheological properties of BCP slurries were studied. The slurry with 65 wt. % of nano-sized BCP powders showed a relatively low viscosity of 400 mPa.s at the 50 s^-1 shear rate. It was found that the optimal photoinitiator concentration was tightly associated with the energy dosage in the DLP process. Subsequently, thermogravimetric analysis (TGA) was performed for DLP-formed green bodies to analyze their thermal decomposition, which led to the determination of the debinding strategy for obtaining crack-free BCP porous scaffolds with desired mechanical and biological properties. Furthermore, the effects of sintering temperature, with 1100, 1200 and 1300 degrees Celsius being used, on the shrinkage, phase constitution, surface roughness, hardness, compressive properties and <i>in vitro</i> biological performance were comprehensively investigated. Results showed that BCP scaffolds sintered at the three respective temperatures exhibited good biocompatibility. Importantly, it was revealed that scaffolds sintered at 1300 degree Celsius had better mechanical properties, higher cell proliferation rates, better cell spreading morphology and homogeneous bone-like apatite formation ability than those sintered at other temperatures. Finally, 3D scaffolds ranging from 300μm to 1mm in pore size were successfully made with high accuracy and fidelity. This study has demonstrated the great potential of DLP 3D printing technology for constructing functional BCP bioceramic scaffolds for bone tissue regeneration.