Advisory Committee Chair
Palaniappan Sethu
Advisory Committee Members
Ho-Wook Jun
Uday K Vaidya
Document Type
Thesis
Date of Award
2015
Degree Name by School
Master of Science in Biomedical Engineering (MSBME) School of Engineering
Abstract
The tremendous quality of life impact notwithstanding, cardiovascular diseases and Cancer add up to over US$ 700bn each year in financial costs alone. Aging and population growth are expected to further expand the problem space while drug research and development remain expensive. However, preclinical costs can be substantially mitigated by substituting animal models with in vitro devices that accurately model human cardiovascular transport. Here we present a novel physiologically relevant lab-on-a-brane that simulates in vivo pressure, flow, strain, and shear waveforms associated with normal and pathological conditions in large and small blood vessels for studying molecular transport across the endothelial monolayer. The device builds upon previously demonstrated integrated microfluidic loop design by: (a) introducing nanoscale pores in the substrate membrane to enable transmembrane molecular transport, (b) transforming the substrate membrane into a nanofibrous matrix for 3D smooth muscle cell (SMC) tissue culture, (c) integrating electrospinning fabrication methods, (d) engineering an invertible sandwich cell culture device architecture, and (e) devising a healthy co-culture mechanism for human arterial endothelial cell (HAEC) monolayer and multiple layers of human smooth muscle cells (HSMC) to accurately mimic arterial anatomy. Structural and mechanical characterization was conducted using confocal microscopy, SEM, stress/strain analysis, and infrared spectroscopy. Transport was characterized using FITC-Dextran hydraulic permeability protocol. Structure and transport characterization successfully demonstrate device viability as a physiologically relevant arterial mimic for testing transendothelial transport. Thus, our lab-on-a-brane provides a highly effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in pre-clinical testing, clinical trials cost from false starts, and time-to-market. Furthermore, this platform can be easily configured for testing targeted therapeutic delivery and in multiple simultaneous arrays for personalized and precision medicine applications.
Recommended Citation
Budhwani, Karim I., "Lab-On-A-Brane: A Novel Physiologically Relevant Planar Arterial Model to Study Transendothelial Transport" (2015). All ETDs from UAB. 1286.
https://digitalcommons.library.uab.edu/etd-collection/1286