# "Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model

> **NIH NIH UG3** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $539,344

## Abstract

Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder that results in premature and accelerated
aging, while accumulation of progerin also occurs during physiological aging. Notably, one of the major targets
of HGPS is the cardiovascular system, which are mechanically active tissues. Typical symptoms include
hypertension, myocardial infarction, congestive heart failure, calcific aortic stenosis, and peripheral
atherosclerosis. For example, autopsy findings have illustrated profound loss of vascular smooth muscle cells
(SMCs) in the medial layer of large arteries, such as the aorta and carotid arteries, with replacement by
collagen and extracellular matrix. Vascular wall echodensity is also increased in HGPS patients associated
with exaggerated fibrotic adventitia formation. The overarching goal of this proposal is to optimize a biomimetic
HGPS-on-a-chip system generated with patient-derived fibroblasts (FBs), SMCs, and endothelial cells (ECs)
that allow application of relevant cyclic stretch for performing ‘clinical trials’ or informing clinical trial designs for
HGPS patients. In particular, we will generate a whole-thermoplastic microfluidic system with a dual-layer
blood vessel-mimicking structure. Based on our preliminary device previously already reported, the proposed
system will be whole-thermoplastic consisting of two channels separated by a thin thermoplastic polyurethane
(TPU) membrane. On top, layers will include a collagen hydrogel encapsulating FBs (adventitia) and an elastin
hydrogel embedded with SMCs (media), post-seeded again with a monolayer of ECs. This methodology
recreates the in vivo microenvironment of blood vessels to faithfully model pathological changes in HGPS.

## Key facts

- **NIH application ID:** 10038138
- **Project number:** 1UG3TR003274-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Y. Shrike Zhang
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $539,344
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038138

## Citation

> US National Institutes of Health, RePORTER application 10038138, "Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model (1UG3TR003274-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10038138. Licensed CC0.

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