Item Details

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