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Three-Dimensional Models for the Study of Hepatic Lipid Metabolism

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title
Three-Dimensional Models for the Study of Hepatic Lipid Metabolism
author
Kirk, Lindsey Madison
abstract
The liver contributes to energy homeostasis in the body by regulating and performing the metabolism of lipids. While this is a significant function of the in vivo liver, current in vitro models have largely ignored this function when performing characterization. Current 3D hepatic models focus primarily on what are termed ‘basic’ functions (i.e., the production of albumin and urea), metabolism of drug compounds, and the development of representative disease models to aid in drug discovery and evaluation. It is well understood within the field of tissue engineering that the properties of the scaffold material used in the formation of 3D models have direct results in regards to cell viability, organization, and functional outputs driven through mimics of what, in vivo, would be cell-extracellular matrix interactions. In the body, these interactions translate mechanical extracellular information into biochemical signals that can be received and understood by the cell. In regards to 3D models, these interactions can be harnessed to improve model fidelity and manipulated to better our understanding of the pathways impacted by these signals. Therefore, in this dissertation we aimed to utilize tissue engineering techniques to better our understanding of how cell-ECM interactions impact lipid metabolism int he liver, in order to build improved in vitro models and harness them to evaluate bioactive lipids for their efficacy as disease treatments. These experiments were performed in three aims:1. Validate the lipid metabolic functionality of a 3D hepatic model and quantify the impact of varying scaffold materials on these outputs. 2. Utilize what we learned from aim 1 to design an in vitro model of the early-stage fibrotic liver within a manipulable hydrogel scaffold and harness this platform to explore the interactions between cell-ECM interactions and the anti-fibrotic capabilities of the bioactive omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA). 3. Harness this platform to explore how timing of EPA administration in regards to the fibrotic injury impacts its effectiveness.
subject
Fibrosis
Lipid Metabolism
Liver
PUFA
Tissue Engineering
contributor
Rahbar, Elaheh (advisor)
Skardal, Aleksander (committee member)
Chuang Key, Chia-Chi (committee member)
Rajagopalan, Padma (committee member)
Soker, Shay (committee member)
date
2023-09-08T08:35:21Z (accessioned)
2023 (issued)
degree
Biomedical Engineering (discipline)
embargo
2025-09-07 (terms)
2025-09-07 (liftdate)
identifier
http://hdl.handle.net/10339/102603 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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