DESIGN AND DEVELOPMENT OF TISSUE ENGINEERING SCAFFOLDS USING ADDITIVE MANUFACTURING

Abstract

Additive Manufacturing (AM), also known as 3D printing, is an advanced manufacturing process to fabricate a 3D part by adding material in a layer-by-layer fashion. The AM process offers multiple advantages due to its additive approach, including design freedom, no assembly required, customized products, fast and efficient production, design flexibility, and minimal material wastage. Besides this, these AM techniques are also less hazardous to the environment than Conventional Manufacturing (CM). Due to various advantages, AM is increasingly used in a wide range of industries, including aerospace, automotive, fashion, sports, biomedical, etc. In the field of biomedical industries, AM finds application in the production of pre-surgery planning assisting models, research testing, learning models, customized prosthetics, hearing aids, surgical instruments, drug delivery devices, patient-specific implants, and Tissue Engineering (TE). Amongst various biomedical applications, TE is an emerging multidisciplinary area with a primary focus on regenerating or repairing damaged tissues in the human body with artificial scaffold material. The vital components of TE are scaffold, growth factor, and cells. A scaffold is a threedimensional porous structure, typically made up of biocompatible materials that support cell proliferation and cell adhesion, which can withstand external loading throughout the process of new bone tissue regeneration. However, the scaffold construct possesses mechanical properties similar to that of host bone tissue. Bone is a highly diverse and dynamic tissue, both functionally and structurally. The trabecular or cancellous bone is found at the end part of long bones and in the vertebral bodies. It is heterogeneous and has high porosity. In addition, it also acts as the prominent load-bearing bone in the vertebral bodies that transfers load from joints to the cortical bone. However, fragility fractures occur in the region of trabecular bone due to trauma or bone disease like osteoporosis. The major challenge in TE is to develop bio-material and scaffold that meets the requirements of native tissues in terms of biological, physical, and mechanical properties. Therefore, in this study, porous scaffolds have been fabricated using two of the most widely used AM techniques, which are FDM and SLA. The scaffolds were printed so as to be compatible with the trabecular bone for Bone Tissue Engineering (BTE) in terms of mechanical strength and tissue-building performance.The present research work is focused on the design and development of TE scaffold with polymerbased bio-composite material using AM. In this regard, several experimental investigations have been done to design and mimic the trabecular scaffold for TE. However, the experimental investigation to design, manufacture, and carry out in-vitro testing of native scaffold is a time and material-consuming process. Hence, a Finite Element Method (FEM) or computational approach has been done to analyze the mechanical behavior, perfusion bioreactor test, and degradation of the designed scaffolds. Initially, different types of scaffolds have been designed with interconnected pore architectures that can be applicable for trabecular bone TE. Consequently, compressive structural analysis has been performed using FEM to forecast the mechanical performance of the scaffolds. A Computational Fluid Dynamic (CFD) analysis was also performed to ascertain the fluid pressure distribution, velocity profile, wall shear stress, strain rate, and permeability of scaffolds. The interconnected pore architecture of the scaffolds played a crucial role in enhancing the mechanical properties and fluid flow characteristics. The FEM-based study can provide a straightforward prediction of the scaffold suitability in terms of mechanical strength, perfusion, and degradation behavior. Furthermore, four nature-inspired structure-based scaffolds have been fabricated through FDM to investigate their potential use in tissue engineering implants along with shape memory effect properties. In order to enhance the mechanical properties and shape-memory behavior, the PLA matrix was reinforced with CaP particles, and its effectiveness has been tested by varying weight percent of CaP. In this regard, various thermo-mechanical and shape memory effect tests have been carried out. Additionally, the material characterization and surface integrity have also been analyzed. These results were processed to examine the overall potential of this attempt to obtain a 4D printed self-fitting implant having enhanced traits of shape memory behavior. Though photo-crosslinkable Poly(ethylene glycol) diacrylate (PEGDA) has outstanding biocompatibility and biophysical properties for tissue engineering, its scope is limited to loadbearing applications. Thus, the mechanical and tribological properties of PEGDA has been enhanced by reinforcing Vitreous Carbon (VC) bioceramic. The VC has been added in PEGDA with different weight % in the range of 0 - 5 %. Initially, the prepared composite resins have been characterized using sedimentation and rheological tests to ascertain the printability for SLA technique. Consequently, the parts have been fabricated using SLA process, and printed material characterization has been investigated using thermal, physical characterization tests along with imagery and surface examinations. Additionally, mechanical and tribological properties of PEGDA/VC composites have been investigated. Further, the study also focused on investigating the biological properties of PEGDA/VC composites developed through SLA. The tribo-mechanical properties and biocompatibility of these composites were investigated. Also, the PEGDA/VC scaffold has been developed with natureinspired structure like honeycomb architecture and its compressive strength has been examined. Furthermore, other physical and degradation tests has been performed to validate the suitability of PEGDA/VC composite scaffold in BTE applications. The computational works, biomaterials developed, designs created and the relevant results presented in this thesis work can act as guiding source for the future research works that explore the capabilities of additive manufacturing in the field of biomedical industry.