UH3TR003274
Cooperative Agreement
Overview
Grant Description
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model - 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.
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.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Massachusetts
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the End Date has been extended from 07/31/25 to 07/31/26 and the total obligations have increased 230% from $539,316 to $1,780,605.
Brigham & Womens Hospital was awarded
Clinical Trials on a Premature Vascular Aging-on-a-Chip Model
Cooperative Agreement UH3TR003274
worth $1,780,605
from National Center for Advancing Translational Sciences in August 2020 with work to be completed primarily in Massachusetts United States.
The grant
has a duration of 6 years and
was awarded through assistance program 93.350 National Center for Advancing Translational Sciences.
The Cooperative Agreement was awarded through grant opportunity "Clinical Trials" on a Chip: Tissue Chips to Inform Clinical Trial Design and Implementation in Precision Medicine (UG3/UH3 - Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 7/21/25
Period of Performance
8/1/20
Start Date
7/31/26
End Date
Funding Split
$1.8M
Federal Obligation
$0.0
Non-Federal Obligation
$1.8M
Total Obligated
Activity Timeline
Transaction History
Modifications to UH3TR003274
Additional Detail
Award ID FAIN
UH3TR003274
SAI Number
UH3TR003274-3027805647
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NR00 NIH National Center for Advancing Translational Sciences
Funding Office
75NR00 NIH National Center for Advancing Translational Sciences
Awardee UEI
QN6MS4VN7BD1
Awardee CAGE
0W3J1
Performance District
MA-90
Senators
Edward Markey
Elizabeth Warren
Elizabeth Warren
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Center for Advancing Translational Sciences, National Institutes of Health, Health and Human Services (075-0875) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,158,716 | 94% |
| National Institute of Child Health and Human Development, National Institutes of Health, Health and Human Services (075-0844) | Health research and training | Grants, subsidies, and contributions (41.0) | $67,641 | 6% |
Modified: 7/21/25