Date of Award

Summer 8-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical & Computer Engineering

Program/Concentration

Biomedical Engineering

Committee Director

Julie Hao

Committee Director

Robert Bruno

Committee Member

Patrick Sachs (Co-Advisor)

Committee Member

Venkat Maruthamuthu

Abstract

Previous work from our laboratory has demonstrated the use of an accessible, open- source 3D Bioprinter can be used to produce mammary systems and understand their development. Specifically, these have culminated in projects that have allowed for the reliable in vitro generation of mammary and neuro (ectoderm) organoid and tumoroid structures within patient, foreign, and otherwise synthetic extracellular matrices. However, two problems were presented that required exploration: application of these results to mouse models and use of cells with our system concerning non-epithelial, mesoderm and endoderm lines. Firstly, it was unknown if mouse cells would behave the same as 3D bioprinted human cells and if divested mouse mammary fat pads would accept in vitro structures created from our 3D bioprinting system. Secondly, it was not known if 3D bioprinted, immortalized epithelial cells from the mesoderm and endoderm germ layers would form organoids and tumoroids when 3D bioprinted with our protocols, and if in vitro chimeric structures could be created from them. We developed protocols to answer these questions. In the case of mouse models, we created protocols for generating organoid and tumoroid structures from mouse mammary epithelial and tumor cells in vitro. We then tested the transplantabilty of both mouse and human bioprinted organoids into cleared mouse mammary fat pads, examining host response and organoid fate. In the case of the non-ectoderm cell lines, we created protocols for the generation of singular and chimeric structures from these cell lines. We found that our 3D bioprinting system both can produce reliable organoids from immortalized, non-tumorigenic mouse cell lines that can be transplanted and survive, but also that our 3D bioprinting system is not limited to just mammary and neuro ectoderm cell lines in the production of organoids, tumoroids, and chimeric structures. Primary explant cells, as well as cell lines from the mesoderm and endoderm can be similarly printed to create these structures. In short, our 3D bioprinting system is adaptable to the investigation of cell fate and structural development of tissues from cell lines from all 3 germ layers.

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DOI

10.25777/ypvn-8q11

ISBN

9798352694411

ORCID

0000-0002-1289-5302

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Available for download on Friday, October 04, 2024

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