BioE PhD Defense Presentation- Josh Hooks

Advisor: 

J. Brandon Dixon, Ph.D. (ME/Georgia Institute of Technology)

Committee:

Andrés J. García, Ph.D. (ME/Georgia Institute of Technology)

C. Ross Ethier, Ph.D. (BME/(Georgia Institute of Technology)

Michael Davis, Ph.D. (BME/Georgia Institute of Technology & Emory University)

Mariappan Muthuchamy, Ph.D. (Medical Physiology/Texas A&M)

Title: The Role of Loading and the Microenvironment on the Regulation of Lymphatic Function and Health

Abstract:  

The lymphatic system is composed of vessels and nodes and exists in almost all of the soft tissue of your body. It plays a large role in maintain fluid homeostasis, immune cell trafficking, and lipid transport. Interstitial fluid that enters the lymphatic system through initial lymphatics is deemed “lymph” and is transported from wherever anatomical region it is collected to the blood circulation. Unlike the venous system, lymphatics  have no heart to act as a centralized pump and lymphatic vessels must act as the conduit for fluid flow and an active pump to drive lymph flow. Lymphatic dysfunction often leads to the development of swelling known as lymphedema. This buildup of fluid alters loading conditions of the local lymphatic network and lymphedema eventually leads to fibrosis and remodeling of the interstitium and lymphatic vessels. The relationship between how remodeling of these extracellular matrices (ECM) is a result of lymphatic dysfunction and/or drives further lymphatic dysfunction is not clearly understood. We present multiple studies utilizing engineering tools to better understand how the biomechanical properties and loading of the extracellular matrix regulate lymphatic function. We establish a healthy and disease lymphatic muscle cell (LMC) line and explore how LMC phenotype impact their response to 2D culture conditions. We demonstrate regulation of LMC molecular pathway expression via physiologically relevant levels of cyclic stretch. In addition, we demonstrate the use of modular polyethylene glycol (PEG) based hydrogels to explore the sensitivity of sprouting lymphangiogenesis to properties of the extracellular matrix. PEG gels can be formulated to produce a robust sprouting network that is sensitive to a variety of molecular regulator. Finally, we present results demonstrating that the PEG hydrogels can be used to successfully transplant lymphatic tissue after damage to local lymphatic collecting vessel or lymph nodes. Tissue transplanted with this method becomes functionally incorporated into the local lymphatic network.