# Improving Tissue Engineered Vascular Graft Performance via Computational Modeling

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2021 · $882,339

## Abstract

PROJECT SUMMARY
First-in-human studies by our group demonstrated that our polymer-based tissue engineered vascular grafts
(TEVGs) represent an exciting new treatment option for children afflicted with congenital heart disease. In
particular, the natural evolution of these grafts from a biodegradable tubular scaffold seeded with autologous
cells to a neovessel consisting of native cells and extracellular matrix represents the first graft with true “growth
potential”, which could eliminate problems associated with somatic overgrowth, the process by which patients
outgrow their graft. Nevertheless, widespread clinical adaptation of these TEVGs to treat children with
congenital heart disease has been slowed by a high incidence of “stenosis” even though angioplasty can be
used to safely manage this complication. Recent findings from our group suggest, however, that the observed
early narrowing of the TEVG that has been interpreted as stenosis may actually resolve naturally and simply
be a part of its normal natural history, thus rendering angioplasty not needed or even ill advised. There is a
pressing need to understand better the natural history of neovessel formation.
Toward this end, we developed a large animal (sheep) model wherein implanted TEVGs phenocopy human
grafts, that is, some develop a narrowing while others do not. We submit that (i) this animal model can provide
longitudinal data (in vivo geometric & hemodynamic, in vitro biomechanical, and cell biological & histological)
that are needed to build a novel computational model of TEVG development and (ii) such a computational
model can provide unique insight into the natural history of TEVG development as well as a predictive
capability that will enable better informed decisions regarding potential interventional treatment (angioplasty)
during TEVG development. To this end, our proposed “fluid-solid-growth” model will integrate validated
subject-specific fluid-solid interaction and vascular growth and remodeling simulations in three dimensions to
quantify the natural history of TEVG development in vivo, including potential narrowing and the need to treat
with angioplasty or not. The model will be informed and validated using in vivo sheep data, and its predictive
capability verified in prospective model-guided angioplasty procedures. The resulting computational framework
will enable the first three-dimensional, subject-specific fluid-solid-growth vascular simulations, which will
improve the use and future design of TEVGs for congenital surgery as well as have broad utility for predicting
disease progression in diverse cardiovascular applications that are driven by immuno- or mechano-biological
mechanisms. This work will be accomplished by bringing together expertise from three complementary groups,
having a track record of prior accomplishments, to advance the use of a promising technology that has the
potential to impact significantly the well being of those afflicted with congenital card...

## Key facts

- **NIH application ID:** 10082302
- **Project number:** 5R01HL139796-04
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Jay D. Humphrey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $882,339
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-04-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082302

## Citation

> US National Institutes of Health, RePORTER application 10082302, Improving Tissue Engineered Vascular Graft Performance via Computational Modeling (5R01HL139796-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082302. Licensed CC0.

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