Three-Dimensional Printing of Polymer Composite Scaffolds for Bone Tissue Engineering and Bone Tumor Models

Abstract

Three-dimensional (3D) printing provides an avenue for efficient, automatic, and repeatable fabrication of tissue engineering scaffolds with highly controlled architecture. Unlike other conventional processing methods, 3D printing is dictated by a layer-by-layer assembly, allowing the fabrication of tunable and gradient architectures. 3D printing is amenable to the incorporation of synthetic or natural materials, cells, and other molecules to mimic the physiological structure of native tissue. Additionally, complex geometries can be designed to accommodate patient-specific defects. This thesis investigates the development of an acellular 3D printed scaffold presenting tunable gradients of pores and ceramic composites for bone tissue engineering and tumor modeling. In order to fabricate heterogeneous scaffolds, we have developed a platform to systematically optimize biomaterial formulations for compatibility with both open-source and commercial extrusion-based 3D printing technologies. We have evaluated the internal geometry, porosity, mechanical properties, rheological properties, and biological properties of 3D printed scaffolds using polymeric and ceramic biomaterials. Based on a large body of data, we have developed statistical models to predict internal scaffold geometry based on inputs of printing parameters and printing solution composition. The ability to predict scaffold architecture prior to printing saves processing time and material waste and would allow efficient customization of porosity, mechanical properties, and composite distribution of bone implants. This work has the potential to be applied to a wide variety of biomaterials and extrusion-based 3D printing systems. Furthermore, we have investigated the use of gradient scaffolds for their relevance in mimicking the heterogeneous tumor microenvironment. We have employed computational modeling to predict the performance of 3D printed gradient scaffolds with bone tumor cells under flow perfusion. A 3D printed scaffold is first conceived by designing a computer-aided design (CAD) file. By leveraging the ideal architecture from the CAD file and non-invasive imaging techniques like micro-computed tomography (μCT), it is possible to understand and compare fluid dynamics computationally prior to running an experiment under flow perfusion. We were able to optimize the flow rate to model physiologically relevant levels of shear stress for the culture of tumor cells on 3D pore gradient scaffolds in a flow perfusion bioreactor. In this work, we have demonstrated the versatility of combining biomaterials with extrusion-based printing for both tissue engineering and tumor modeling applications. We have leveraged the benefits of 3D printing technologies and synthetic biomaterials to fabricate scaffolds with both controlled structural and compositional gradients.