Optimization of Biomanufacturing process for Tissue Engineering applications

University of Brescia 2024 Thesis
R. Rovetta

In recent years, tissue engineering has experienced significant advancements, mostly driven by the emergence of additive manufacturing technologies and the integration of biomaterials and cells. This advanced technique enables the creation of intricate structures with diverse components and properties, specifically designed for use in biomedical applications. The primary benefit of this technology is its ability to be customised, which helps minimise post-operative difficulties for patients with orthopaedic diseases and those undergoing tissue transplants. For this purpose, the essential components can be synthesised by the patient’s own cells. However, there are still other obstacles that need to be addressed in order to get satisfactory 3D printed structures. One key problem is the need to optimise the biomaterial to meet both biocompatibility and printability criteria. In addition, the production of scaffolds for tissue engineering is a complex procedure as it requires the built structures to closely mimic the extracellular matrix in order to create a functional tissue. The key goal is to produce 3D scaffolds composed of multiple-scale structures made of cell-loaded bioinks. The objective of this thesis is to create 3D scaffolds for tissue engineering applications using additive manufacturing technologies. In order to accomplish this, the selection of technology and material is of crucial significance. Therefore, it is essential to optimise both the printing technique and the selected biomaterial. The literature can assist in determining the essential parameters to be optimised in this regard. However, each specific application necessitates a thorough investigation due to the diverse and unique combinations of material technology and post-processing methods. The technologies utilised are electrospinning, extrusion-based bioprinting, and laser powder bed fusion. The diverse range of technology provides an overview of how scaffolds can be constructed to meet various scale specifications. Extrusion-based bioprinting utilises hydrogels, including both synthetic and natural variants, as scaffolding materials. These hydrogels are chosen because of their ability to closely mimic the extracellular matrix, which is essential for the growth of new tissue. In addition, they exhibit an optimal response to printing factors that are valuable for enhancing the printing process itself, with the aim of producing scaffolds that meet both biological and geometric requirements, including the selection of an appropriate crosslinking method. The Ti6Al4V alloy was used to study the surface properties of an orthopaedic implant. This alloy is specifically suitable for producing orthopaedic implants using laser powder bed fusion technology. To summarise, this thesis concentrates on the production of 3D scaffolds using additive manufacturing for tissue engineering applications. Every technology posed distinct challenges and concerns that needed to be resolved. In the end, the examination and refinement of the printing parameters and post-processing operations yielded favourable outcomes and improved knowledge of the processes.