Heart‐On‐a‐Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell‐ and Tissue‐Scale Contractile Stresses

TL;DR

A heart-on-a-chip device with soft sensors measures real-time mechanical stresses at both cell and tissue levels for drug testing and biomechanical studies.

Contribution

A novel non-destructive optical method using ultrasoft mechanosensors enables multi-scale stress mapping in engineered cardiac tissues.

Findings

eMSGs deform in response to cellular and ECM stresses, allowing real-time lateral and longitudinal stress measurements.

Reduced fibrin concentration in the hydrogel improved contractile frequency, regularity, and force generation.

Pharmacological agents like norepinephrine and blebbistatin showed expected effects on contractile force and inhibition.

Abstract

Heart‐on‐a‐chip platforms aim to recapitulate cardiac tissue structure and function in vitro. Traditionally, microfabricated pillars are used to estimate contractile forces based on pillar deflection. However, this approach measures only global forces at the pillar interface and lacks the spatial resolution needed to capture local mechanical stresses. In this study, we present a non‐destructive optical method for continuous, multi‐scale stress mapping using ultrasoft edge‐labeled micro‐spherical stress gauges (eMSGs). These embedded mechanosensors visibly deform in response to cellular and extracellular matrix (ECM)‐generated stresses, enabling real‐time measurements at cell and tissue scales. Our platform features dual cell‐seeding chambers with flexible polydimethylsiloxane pillars, into which neonatal rat cardiomyocytes are seeded within a fibrin/Geltrex hydrogel containing eMSGs. Over time, tissues compacted, aligned, and exhibited spontaneous contractions and calcium transients. By modulating ECM composition, we found that reduced fibrin concentration enhanced contractile frequency, regularity, and force generation. Analysis of eMSG deformation enabled calculation of lateral and longitudinal stresses, revealing the impact of compaction and contraction on local mechanics. Finally, drug testing was performed using norepinephrine, which enhanced contractile force, and blebbistatin, which inhibited contraction, demonstrating robust pharmacological responsiveness. This platform provides a powerful tool for real‐time biomechanical analysis and drug testing in engineered cardiac tissues.

We present a heart‐on‐a‐chip platform embedded with ultrasoft mechanosensors for real‐time, multi‐scale stress mapping in engineered cardiac tissues. The system enables simultaneous quantification of local cell‐generated stresses and global tissue contractile forces. Functional responses to extracellular matrix modulation and pharmacological agents demonstrate the platform's utility for biomechanical studies and drug screening applications.

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