University thesis:
Dissertation, Universität Freiburg, 2023
Footnote:
Description:
Abstract: Three-dimensional bioprinting (3DBP) is a promising fabrication approach in tissue engineering, as it offers precise and customized control over the relationship between structures and cells. In the 3DBP space, extrusion-based bioprinting (EBB) stands out as the most accessible and practical approach with the potential to bridge the gap between laboratory research and clinical applications. One crucial aspect of successful translation is the development of validated bioinks which encompass simplicity in design, use, and implementation. <br>This dissertation first introduces a bioprinting system that utilizes thermally crosslinkable carboxylated agarose (CA)-based bioinks. Next, using this system, the creation of high-aspect-ratio and complex constructs without the need for additional supporting phases or extensive post-processing is described. Extending on these findings, the utility of these novel bioinks in printing anatomically relevant and equivalent structures is presented. Furthermore, using EBB, the engineering of single-matrix constructs containing a high concentration of human mesenchymal stromal cells (MSCs) is demonstrated. By identifying conditions that promote spontaneous aggregation of MSCs, MSCs-laden structures that can stably undergo differentiation into cartilaginous templates in vitro were achieved. Next, the remodeling of these constructs in vivo in an ectopic model was exploited to engineer bone of bespoke shape. The final section of the dissertation describes the development of a composite bioink, containing CA and gelatin, a thermoresponsive biopolymer. Using a paradigm for evaluation using iterative output from rheological and biological characterization, bioinks that can support human nasal chondrocytes and promote the uniform deposition of cartilage extracellular matrix was developed. The bioinks developed in this dissertation lay the foundation for exploiting 3DBP in bone and cartilage repair