BME PhD Proposal Presentation: Kelley A. Garvin

Promoting Angiogenesis within Three-Dimensional Engineered Tissue Using Ultrasound

By Kelley A. Garvin

Co-Supervised by Prof. Diane Dalecki and Prof. Denise Hocking

Abstract

Technological advancements in the field of tissue engineering could save the lives of thousands of organ transplant patients who die each year while waiting for donor organs. Currently, one of the primary challenges preventing tissue engineers from developing replacement tissues and organs more than a few millimeters in size is the need to vascularize the tissue to effectively deliver essential oxygen and nutrients and maintain viability and function. Promoting angiogenesis in vitro has emerged as a promising strategy to vascularize bioengineered tissue. As such, methodologies that stimulate angiogenic endothelial cell behaviors, such as migration, proliferation, and tubular morphogenesis, could be used to develop neovascular networks within engineered tissue constructs.

In this proposal, I will develop the use of ultrasound technologies to promote angiogenesis within three-dimensional bioengineered tissue. Ultrasound is a form of mechanical energy that can noninvasively and nondestructively interact with tissues at the cell and protein level. My preliminary data indicate that ultrasound standing wave field radiation forces aggregate cells and an essential angiogenic component in the extracellular matrix, fibronectin, into a banded pattern within three-dimensional collagen gels.

My data also shows that ultrasound standing wave field-induced cell banding enhances cell-mediated collagen remodeling and promotes endothelial cell sprouting from endothelial cell bands. These studies, taken together with previous findings that therapeutic ultrasound can enhance angiogenesis by mechanical mechanisms, suggest that mechanical forces associated with ultrasound propagation can affect three key angiogenic regulatory factors the spatial organization of endothelial cells, the organization of the extracellular matrix, and mechanical stimuli. As such, I hypothesize that ultrasound can be used to promote angiogenesis within three-dimensional engineered tissue.

The aims of this proposal are to:

1. use ultrasound standing wave field acoustic radiation forces to control the organization of endothelial cells and extracellular matrix proteins within three-dimensional collagen tissue constructs;
2. investigate the effects of ultrasound-induced mechanical forces on extracellular matrix remodeling and endothelial cell proliferation within three dimensional collagen constructs;
3. and use ultrasound to promote angiogenesis within three-dimensional collagen constructs.

The results of this work will demonstrate that ultrasound is a novel, noninvasive, and nondestructive technology capable of promoting angiogenesis in vitro for the fabrication of vascularized tissue constructs for the field of tissue engineering.