# HUMAN TISSUE ENGINEERED PULSATILE CONDUITS USING ENGINEERED HEART TISSUE OF DEFINED COMPOSITION AND FIBER ORIENTATION

> **NIH NIH F31** · YALE UNIVERSITY · 2020 · $45,520

## Abstract

Abstract:
Engineered heart tissue (EHT) made from human induced pluripotent stem cell-derived ventricular
cardiomyocytes (hiPSC-VCMs) can be used as a promising tool for the cardiovascular therapeutics. Single
ventricle heart defects are a class of congenital disorder where only a single ventricle properly develops.
This can result in mixing of oxygen-rich blood and oxygen-poor blood during circulation, leading to
inefficient oxygen supply to tissues of the body. Additionally, this class of defects places an increased strain
on the single ventricle during contraction. Children born with this disease are commonly treated with the
Fontan procedure to re-route blood flow from the superior and inferior vena cava directly into the pulmonary
artery. Synthetic grafts lined with bone marrow derived stem cells have been used as vascular conduits to
make the connection between the inferior vena cava and the pulmonary artery. However, these synthetic
grafts cannot provide pumping activity to help circulate blood. The purpose of this project is to generate
tissue engineered pulsatile conduits (TEPCs) to aid in circulation by producing contractile force, and thus
an increased driving pressure, to aid in flow through the pulmonary system. The design strategy employed
for TEPC production uses decellularized human umbilical artery as an acellular vascular scaffold because
its mechanical characteristics allow it to maintain patent blood flow in the inferior vena cava. This scaffold is
wrapped with hiPSC-VCM derived EHTs to provide contractile force for the conduit. Decellularized pig heart
tissue is used as a scaffold for generating EHTs because it has an inherent fiber structure that allows for
generation of controllable alignment of myocardial fibers within the tissue. Co-culture EHTs of hiPSC-VCMs
and cardiac fibroblasts were made and tested for contractile force output. Preliminary data shows the
introduction of fibroblasts into the tissue has a positive effect on contractile output. Microvascular networks
will be generated to support thicker TEPC muscle layers and increase overall TEPC pressure generation.
TEPCs will be subjected to an in vitro training regimen consisting of physical and electrical cues to enhance
their contractility and electrical handling properties. A flow bioreactor will provide stretch within the TEPC
lumen to give the tissue mechanical pressures that mimic what will be experienced in rat inferior vena cava.
Electrodes placed within this bioreactor system will provide field stimulation that is intended to mimic the
human developmental environment to coax out more mature electrical characteristics from the hiPSC-
VCMs. To test for basic survival of the graft, a nude rat model will be used to assess basic parameters for
successful engraftment as an inferior vena cava interposition graft. Refinement and optimization of this
robust design strategy for producing TEPCs developed in this study will lay the groundwork for testing the
construct’...

## Key facts

- **NIH application ID:** 9988960
- **Project number:** 5F31HL143928-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Christopher W Anderson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988960

## Citation

> US National Institutes of Health, RePORTER application 9988960, HUMAN TISSUE ENGINEERED PULSATILE CONDUITS USING ENGINEERED HEART TISSUE OF DEFINED COMPOSITION AND FIBER ORIENTATION (5F31HL143928-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9988960. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
