# Harnessing biophysical cues to spatially organize developing cardiac organoids

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $69,127

## Abstract

Abstract:
Current 2D in vitro monocultures and animal models fall short in accurately modeling cardiovascular genetic
disorders, leading to inadequate therapeutic development. Recent advances have now centered on 3D organoid
models due to their improved cellular heterogeneity. However, cardiac organoids still lack crucial structural
characteristics, cell types, and cellular organization which limits their utility. While recent approaches focus on
modifying morphogens, none have used mechanical cues as guides for the differentiation process. Preliminary
data presented within reveal that microconfining stem cell colonies on compliant substrates facilitates cardiac
organoid generation and release, with substrate stiffness and geometric asymmetry influencing the spatial
organization of organoid structure. The research proposed in this fellowship will explore these findings further to
develop a roadmap for engineering-in the missing structural components. By modulating matrix mechanics, we
aim to replicate developmental stiffness, guiding traction stresses and cell polarization during early differentiation
stages. Gradients and temporal changes of stiffness may push towards cardiac mesoderm specification via
presentation of a more physiologically representative mechanical environment. Controlling local cell densities
and geometric confinement may further play a role in guiding final organoid architecture and cell heterogeneity
and distribution. Overall, the goal is this work is to establish a platform that can reproducibly create cardiac
organoids with tunable spatial control for drug screening applications, with scope for application towards other
organoid types.

## Key facts

- **NIH application ID:** 10998320
- **Project number:** 1F32HL176176-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Thomas Gregory Molley
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $69,127
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998320

## Citation

> US National Institutes of Health, RePORTER application 10998320, Harnessing biophysical cues to spatially organize developing cardiac organoids (1F32HL176176-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10998320. Licensed CC0.

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