# Generating multilayered engineered heart tissue patches to mimic physiological thickness and function using open microfluidics

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2021 · $41,159

## Abstract

PROJECT SUMMARY/ABSTRACT
Heart disease is the leading cause of death in the U.S., often driven by irreversible cardiac tissue damage
leading to heart failure. Cardiac tissue does not naturally regenerate, and thus is an important area of focus for
tissue engineering. Previous development into engineered heart tissue (EHT) "patches" with some functional
architecture such as pre-patterned vasculature and alignment has shown promising results when implanted
into small animal models. Moreover, injected stem cells and implanted cardiac "sheets" have shown some
success in restoring some cardiac function when implanted into infarcted hearts of large animals or humans.
Despite these successes, scaling EHT that incorporates important functional features such as vascularization
and alignment to a physiological thickness (cm-scale) remains a major engineering challenge.
The overarching goal of this proposal is to generate in vitro physiologically thick heart tissue patches that can
ultimately be implanted into patients to replace damaged tissue. Two key considerations for recapitulating
native tissue are (1) cardiac tissue is highly vascularized, and (2) alignment of cells and extracellular matrix
within each physiological layer is critical to function. We address these challenges utilizing novel open
microfluidic patterning approaches. Our open microfluidic technological advancement offers unique benefits to
EHT; for example, it is compatible with virtually any hydrogel, including standard extracellular matrix material
such as collagen and fibrin, used extensively for EHT. It is also compatible with specialized stimuli-responsive
engineered hydrogels, opening up possibilities for complex engineered tissues with spatial and temporal
control. Further, the flow of precursor fluid is driven by passive surface tension forces; thus, sensitive stem-cell-
derived cells are not exposed to shear stress from extrusion through a needle or photochemical crosslinking,
which are requirements for other tissue fabrication techniques such as 3D bioprinting. Finally, a large area (cm-
scale) can be patterned with a single pipetting step, making this fabrication approach ideal for generating large
(cm-scale) tissues. In this proposal, I apply these unique attributes of open microfluidic pattering to EHT.
Specifically, the ability to pattern enzymatically degradable gels through a background of standard cell culture
ECM materials such as collagen or fibrin enables the patterning of complex vasculature in three dimensions. I
will also take advantage of previously demonstrated modular stacking of open microfluidic devices and
suspended microfluidics to generate aligned EHT patches. In these patches, the tissue is anchored on either
end, inducing ECM remodeling and alignment. Each layer is generated and aligned independently. Then, they
are stacked together at an angle from the previous layer, creating a multilayered tissue mimicking the heart's
helical tissue fiber alignment. As...

## Key facts

- **NIH application ID:** 10230405
- **Project number:** 1F30HL158030-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Amanda Jean Haack
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,159
- **Award type:** 1
- **Project period:** 2021-06-16 → 2025-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230405

## Citation

> US National Institutes of Health, RePORTER application 10230405, Generating multilayered engineered heart tissue patches to mimic physiological thickness and function using open microfluidics (1F30HL158030-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10230405. Licensed CC0.

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