CAREER: An Integrated Transvascular Biotransport Research and Educational Initiative

University Of Tennessee Knoxville, Knoxville TN

Investigators

Abstract

0238905 English The overall goal of this project is to integrate a biomedical engineering research program of vascular biotransport processes with an educational program that targets graduate, undergraduate, and underrepresented middle school levels of education. To meet this goal, this proposal exploits and strengthens a unique collaborative environment between The University of Tennessee, Oak Ridge National Laboratory, The University of Tennessee Vascular Research Laboratory, and two underrepresented middle schools in the East Tennessee area. The primary objective of this research is to investigate endothelial cell barrier function using synthetic hydrogel scaffolds with predefined surface properties and a novel electrical impedance model. The intellectual merit of the research component lies in the integration and application of concepts from electrical, mechanical, and chemical engineering to investigating an important and fundamental problem in vascular biology. Using a combination of quantitative modeling techniques, thermodynamically engineered hydrogel scaffolds, and electrical measurements, this study examines how specific receptor mediated and cytoskeletal interactions control endothelial cell barrier function. The central hypothesis of this work is that endothelial cell barrier function is regulated by specific cytoskeletal elements that control cell-cell and cell-matrix coupling. This study tests this hypothesis using a microcontinuum electrical model with cell-cell and cell-matrix adhesion dependent impedances and drugs that target specific cytoskeletal elements. This model is experimentally and numerically validated using biological interventions and a novel tissue engineered endothelial cell and hydrogel matrix structure that permits direct control over cell-matrix specific binding interactions. The outcome of this research will contribute to an understanding of endothelial cell barrier function and cellular-biomaterials interactions and impact several areas of cell biology, tissue engineering, and pharmacology. The overall educational objective is to stimulate efficient learning at graduate, undergraduate and pre-college levels of education. Curriculum development at both the undergraduate and graduate level compliments the proposed research program. As part of the curriculum improvement, a Cellular Fields, Forces and Flows graduate course and a senior/graduate level Cell and Tissue Biotransport Processes course and laboratory are being developed. This proposal targets underprivileged and minority groups at the middle school level and supports an existing minority outreach program at The University of Tennessee.