T18 - Vessel-on-a-Chip Microfluidic Device for Modeling Blood Vessel Vasculature Under Diabetic Conditions

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Kristin L. Hagen

Student
University of California Irvine
Huntington Beach, California, United States

Primary Investigator(s)

Quinton Smith

Assistant Professor
University of California, Irvine
Irvine, California, United States

Co-Author(s)

Eric Wang

Graduate Student
University of California, Irvine
Seattle, Washington, United States
MELISA ANDRADE, PhD

Postdoctoral Scholar
University of California, Irvine
Irvine, California, United States

Introduction: : Diabetes is a chronic illness primarily associated with ineffective blood glucose regulation and insulin production, but it also induces inflammation of the endothelial cells that line the blood vessels, resulting in cardiovascular dysfunction. As a result, cardiovascular disease accounts for 50% of deaths from type II diabetes.

Mouse models and two-dimensional cell culture are the primary methods for studying mechanisms underlying diabetes-induced changes in blood vessels, but they are not entirely representative of human vasculature or its interactions with drugs. To address this gap in research technology, a microfluidic device was designed and fabricated to model the 3D structure, physiological conditions, and cell-drug interactions of a blood vessel in vivo.

Materials and

Methods: : A polydimethylsiloxane (PDMS) microfluidic mold was injected with a collagen (I) gel, through which acupuncture needles were inserted via ports to serve as a sacrificial mold and create a cylindrical scaffold. Upon needle removal, human endothelial and stromal cells were seeded, resulting in their self-organization into a three-dimensional vessel-like structure (Figure 1).

Diabetic conditions were induced by treating vessels with pro-inflammatory cytokines, IL-6 and TNF-a, and high glucose concentration media conditions. Fluorescence microscopy was used to assess changes in extracellular matrix (ECM) deposition, inflammatory marker expression, barrier function, and immune cell adhesion compared to healthy vessels. Vessels were stained for basement protein collagen IV, laminin I, and intracellular adhesion molecule 1 (ICAM-1) expression to measure ECM deposition and inflammation. Barrier integrity and tight junction formation were assessed by measuring the perfusion of FITC-dextran through the blood vessel into the bulk collagen gel over time. Immune cell adhesion was quantified by counting the number of THP-1 monocytes bound to the walls of healthy and treatment vessels.

Finally, experiments were repeated on vessels after treatment with the drug empagliflozin and two Notch inhibitors, L-685458 (a gamma-secretase-inhibitor) and DAPT, to assess the reduction of vessel inflammation and dysfunction.

Results, Conclusions, and Discussions:: Diabetic vessels displayed increased ECM deposition and elevated ICAM-1 expression, as well as disrupted endothelial layer formation (Figure 2). FITC-dextran assays revealed greater leakiness as the fluorescent dye migrated more quickly out of the diabetic vessels (Figure 3), and immune cell adhesion was significantly increased as more monocytes stuck to the walls compared to healthy blood vessels (Figure 4). Initial drug experiments demonstrated how empagliflozin and gamma-secretase-inhibitors reduced ICAM 1expression and monocyte adhesion.

The vessel-on-a-chip model successfully recapitulated features of diabetic vasculature in patients, including inflammation, barrier dysfunction, and immune response. Upregulation of ECM deposition and ICAM 1 expression validate symptoms of vascular inflammation, and increased perfusability points to reduced barrier function of the endothelial cell layer due to malformation of tight junctions between cells. Increased immune cell adhesion to the vessel walls demonstrates the expected immune response and induced vascular changes to inflammatory signals by the endothelial cells. Drug treatments reduced key inflammatory markers and restored some vascular function, supporting the physiological relevance of the microfluidic model.

These findings validate the vessel-on-a-chip as a biomimetic platform for studying the vascular changes in diabetes, as it properly mimics the behavior of both healthy and diabetic blood vessels in vivo. Observing the expected behaviors suggests that the three-dimensional structure of the blood vessel-on-a-chip provides a proper microenvironment for facilitating cell-cell interactions, and may enhance the accuracy of studying drug interactions in vitro.

Preliminary experiments using drugs known to relieve vascular symptoms of diabetes show promise that the blood vessel-on-a-chip can be used as a model to facilitate future drug-discovery efforts and investigate the roles of various pathways involved in the vascular changes caused by diabetes.

Acknowledgements and/or References (Optional): :