Increasing demands for organ transplants and the depleting supply of available organs has heightened the need for alternatives to this growing problem. Tissue engineers strive to regenerate organs in the future; however doing so requires a fundamental understanding of organ development and its key processes. The first chapter of this thesis provides a brief overview of developmentally inspired engineering, specifically in the context of how I approach this challenge in this thesis. The second chapter provides an in depth review of current and past work focused on organ regeneration from a developmentally-inspired perspective, and using tooth formation as a model system. The third chapter describes the design and fabrication of a thermoresponsive polymer inspired by an embryonic induction mechanism, and demonstrates its ability to induce tooth differentiation in vitro and in vivo. This is effectively a 3D `shrink wrap'-like polymer sponge that constricts when it is warmed to body temperature and induces compaction of cells contained within it, hence recapitulating the mesenchymal condensation process that has been shown to be a key induction mechanism that triggers formation of various epithelial organs, including tooth in the embryo. The fourth chapter describes the fabrication of a novel microarray screening platform consisting of a unique set of ECM proteins (collagen VI, tenascin, and combination of the two at different coating densities) on an array of soft substrates (~130-1500 Pa) that are physiologically relevant to the embryonic microenvironment. This technology demonstrated the capacity to analyze combinatorial effects of these ECM proteins and soft substrates on cell density, cell area and odontogenic differentiation in murine mandible embryonic mesenchymal cells. The fifth chapter of this thesis summarizes and discusses the advantages, limitations and future potential of the findings described in the previous two chapters in the context of organ engineering and regeneration. Taken together, the work and results presented in this thesis have led to the development of new insights, approaches and tools for studying organ formation and potentially inducing organ regeneration, which are inspired by key developmental mechanisms used during embryonic organ formation. / Engineering and Applied Sciences

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20280号 / 医博第4239号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 羽賀 博典, 教授 坂井 義治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM