Date on Master's Thesis/Doctoral Dissertation

5-2018

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Williams, Stuart

Committee Co-Chair (if applicable)

Hoying, James

Committee Member

Hoying, James

Committee Member

LeBlanc, Amanda

Committee Member

Slaughter, Mark

Committee Member

Joshua, Irving

Author's Keywords

stromal vascular fraction; angiogenesis; tissue engineering; microvessels; electrospinning; bioprinting

Abstract

This dissertation describes the use of stromal vascular fraction to tissue engineer 3D microvasculature and macrovasculature. Stromal vascular fraction is an easily isolatable cell source from adipose tissue depots. It has demonstrated remarkable potential both in vitro and in vivo for forming microcirculation capable of perfusion upon implantation. SVF is clinically utilized as a therapeutic cell source for anti-inflammation for osteoarthritis and is being studied for ischemic tissue application to stimulate revascularization. The work described herein is divided within four chapters. Chapter I provides an introductory overview and lists the aims and hypothesis for the dissertation. Chapter II describes experiments towards elucidating specific aim 1: determine the mechanism by which SVF forms neovascular networks in 3D fibrin gels in vitro. This was accomplished through a multitude of experiments describing SVF undergoing vasculogenesis and angiogenesis in a 2D automated in vitro assay, and the ability to inhibit these processes via NOTCH and PDGF-B/PDGFR-b interruption. These mechanisms, as well as integrin dependent mechanisms, were analyzed within 3D fibrin and 3D collagen I culture systems as well. It is believed that the activation of the fibrin specific integrin aVb3 plays a role in hyper-stimulating fibrin-embedded endothelial cells in a VEGF dependent manner. Chapter II describes experiments towards understanding specific aim 2: create deliverable tissue units of SVF-derived microvasculature or macrovasculature utilizing bioprinting, and electrospinning technologies. This was accomplished through bioprinting spheroids containing cells embedded in collagen I or fibrin using superhydrophobic surface technology or electrospinning varying porosities of PCL and pressure sodding SVF cells into the material. It is possible to automate and create dosable units of microvascular tissue in spheroid format using SVF cells, ECM such as fibrin or collagen I, and bioprinting technologies. Additionally, it is possible to create blood vessel mimics of multiple porosities in order to retain and allow cellular infiltration within the biomaterial. Chapter IV is an overall summary and conclusion of the dissertation. These studies could hopefully generate more knowledge on the creation of tissue engineered microvasculature and microvasculature for use in treating ischemic cardiomyopathies.

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