Performing Department
Agricultural & Biological Engineering
Non Technical Summary
Approximately one in four Americans are susceptible to developing chronic inflammatory response syndrome as a result of exposure to biotoxins [1]. These biotoxins are typically introduceed into the body via food ingestion. In response to biotoxins, there is an upregulation of inflammatory signals that can potentially affect blood flow dynamics and the vascular endothelium. We propose to create anin vitromodel of engineered endothelium that mimics thein vivomicroenvironment to understand the vascular inflammation. Wehypothesizethat we can probe the underlying mechanisms of vascular inflammation and test novel detection strategies using modelin vitromicrosystems. We will use 3D printing and soft lithography techniques to build our model. Tissue health or pathology will be assessed by measuring gene expression, cell viability, and quantify changes in tissue andcell morphology. We will also monitor blood flow dynamics to understand how food derived factors may influence blood-endothelium interactions. Thegoal of this studyis to detect and understand how food derived factors induce inflammation. We assert that vascular inflammation can signal the presence of biotoxins and the presence of these inflammatory substances may alter endothelium-blood interactions which may lead to organ and tissue damage. This tool can also be used to provide valuable insight into the underlying mechanisms of vascular diseases.Berndtson, Keith. "CHRONIC INFLAMMATORY RESPONSE SYNDROME." (2013).
Animal Health Component
0%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
Develop devices and systems incorporating microfabrication and nanotechnology
Project Methods
We will create a model vessel to recapitulatein vivofeatures of the native vasculature. In order to create this model, we will incorporate 3D printing, micro molding, soft lithography, and photolithography techniques to create a physiologically relevant vascular network model. The channels will be constructed from porcine derived extracellular matrix (ECM) proteins that will serve as a cell growth substratescaffold. The channels will then be seeded with mammalian derived lung, spleen, or liver endothelial cells forming a confluent monolayer which will serve as our "engineered endothelium". We chose these systems becausethey serve as biological filters for the body. Using this system, we can probe the direct effects of food derived factors on the endothelium and investigatehow these factorsmay alter blood interactions andendothelium function. We will assess endothelium function by performing gene expression analysis, live/dead cell assays, and cell morphology studies. We will assess endothelium inflammation by measuring expression of interlukin-1 and vascular cell adhesion molecule-1 (VCAM-1). We will also quantify enhanced blood-endothelium interaction by quantifying blockages that result from cell clustering within microfluidic channels upon exposure to various stresses and food derived factors. Results from this work will be compiled for publication in a scientific journal and presented at relevant conferences.