DEVELOPMENT OF COLLAGEN BIOINKS FOR CARTILAGE BIOPRINTING

158 pagesBioprinting, or the use of three-dimensional printing technology to produce scaffolds and cellularized tissue constructs, is becoming more prominent in the tissue engineering and regenerative medicine fields. However, a major limiting factor to the field remains the development of adequate bioinks. Bioinks must be printable, cell-friendly, and exhibit mechanical properties necessary for construct implantation. Collagen bioinks are promising due to their cell-friendly properties but exhibit weak mechanical properties and slow gelation that present challenges for bioprinting applications. The overall goal of this study is to develop improved collagen bioinks for cartilage bioprinting that exhibit improved mechanics and printability while maintaining cell-friendliness. There are many parameters that can be used to tune the properties of collagen hydrogels, such as collagen concentration, gelation temperature, pepsin treatment, pH, enzymatic crosslinking, photocrosslinking by light activated riboflavin, and non-enzymatic glycation. Despite all this knowledge, except for collagen concentration, none of these parameters have been applied to the development of collagen bioink formulations. Additionally, bioinks are intended to contain encapsulated cells, however, it is not understood how the incorporation of cells could affect the performance of collagen bioinks. This work begins to investigate these collagen-tuning parameters to develop improved collagen bioinks that exhibit high shape fidelity, printability, and cell-friendliness. This was achieved by first determining which rheological properties are best able to predict collagen bioink printability by correlating the rheological properties and printability of collagen bioinks with blue light activated riboflavin crosslinking and pH variations (Chapter 2). The ability to print with cells and for those cells to survive and thrive is a major necessity of bioprinting. Therefore, the effect of the incorporation of cells on collagen bioink rheology and printability and how the printing process affects cell viability was determined (Chapter 3). Lastly, to improve collagen mechanics in a more cell-friendly manner, the effects of crosslinking through non-enzymatic glycation of collagen was investigated (Chapter 4)