# Scalable platform for optimizing human cardiac tissue engineering via optical pacing and on-demand oxygenation

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2022 · $673,613

## Abstract

PROJECT SUMMARY
Induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) are emerging as an invaluable in vitro human
experimental platform for disease modeling, drug discovery, cardiotoxicity screening, gene editing and functional
genomics. For the first time, cardiac electrophysiology has access to a scalable human experimental model,
which, currently, offers the only path to personalized (cardiac) medicine as patient-derived iPS-CMs can be
generated on a progressively faster time scale. The clear potential of this technology motivates efforts to address
the main criticisms facing iPS-CMs, namely the need for further maturation and reduction of phenotype
heterogeneity. As multiple approaches are being pursued to improve iPS-CM maturation and to approximate the
functionality of the adult human myocardium, we argue that combinatorial optimizations necessitate new
high-throughput (HT) technology and automation. The overall goal of this project is to develop and validate
a scalable platform for optimizing cardiac tissue engineering via chronic reconfigurable optical pacing
and “on-demand” oxygenation for gaining mechanistic insights into cardiac metabolism and
electrophysiology, a platform we call ChROME. Chronic electrical stimulation is a viable lead to iPS-CM
maturation, yet it has remained under-explored, specifically as related to the role of mass transport and
oxygenation during such stimulation. Leveraging our expertise in the theoretical and experimental use of
optogenetic tools for cardiac applications (Entcheva) and automation (Kostov, Li, Entcheva, Kay), we propose
to design and validate the first-generation HT-ChROME platform, that will integrate continuous monitoring of key
physiological parameters. Our team’s expertise in optical oxygen sensing (Kostov), in-house manufacturing of
“on-demand” oxygenation nanocarriers (perfluorocarbons, PFC) (Kay) and metabolic characterization (Kay,
Beard) will be applied to address the increased metabolic demands during stimulation. The ability to quantify
“functional maturation” by relevant measures (voltage, calcium, contraction) in a high-throughput manner
(Entcheva) in 2D and 3D cardiac tissue constructs (Vunjak-Novakovic), using our automated platform OptoDyCE
(all-optical dynamic cardiac electrophysiology) is critical in this undertaking. Employing these HT tools and other
imaging and omics modalities (Popratiloff, Horvath), we will elucidate the spectrum of responses triggered by
chronic stimulation of iPS-CMs: beneficial/maturation effects vs. pathological overload effects, depending on
load and oxygenation conditions. The proposed HT-ChROME platform represents a critical step in resolving
issues impeding progress with iPS-CMs to accelerate their wide-spread adoption in basic and translational
applications. The obtained large-scale data will inform a new generation of biophysical models linking human
cardiac metabolism and electrophysiology.

## Key facts

- **NIH application ID:** 10330558
- **Project number:** 5R01HL144157-04
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Emilia Entcheva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $673,613
- **Award type:** 5
- **Project period:** 2019-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330558

## Citation

> US National Institutes of Health, RePORTER application 10330558, Scalable platform for optimizing human cardiac tissue engineering via optical pacing and on-demand oxygenation (5R01HL144157-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10330558. Licensed CC0.

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