A Platform for Assessing Cellular Contractile Function Based on Magnetic Manipulation of Magnetoresponsive Hydrogel Films

Moran Yadid, Mario Hagel, Megan Beldjilali Labro, Baptiste Le Roi, Carina Flaxer, Eli Flaxer, A. Ronny Barnea, Shai Tejman-Yarden, Eric Silberman, Xin Li, Rossana Rauti, Yael Leichtmann-Bardoogo, Hongyan Yuan, Ben M. Maoz

Research output: Contribution to journalArticlepeer-review

Abstract

Despite significant advancements in in vitro cardiac modeling approaches, researchers still lack the capacity to obtain in vitro measurements of a key indicator of cardiac function: contractility, or stroke volume under specific loading conditions—defined as the pressures to which the heart is subjected prior to and during contraction. This work puts forward a platform that creates this capability, by providing a means of dynamically controlling loading conditions in vitro. This dynamic tissue loading platform consists of a thin magnetoresponsive hydrogel cantilever on which 2D engineered myocardial tissue is cultured. Exposing the cantilever to an external magnetic field—generated by positioning magnets at a controlled distance from the cantilever—causes the hydrogel film to stretch, creating tissue load. Next, cell contraction is induced through electrical stimulation, and the force of the contraction is recorded, by measuring the cantilever's deflection. Force–length-based measurements of contractility are then derived, comparable to clinical measurements. In an illustrative application, the platform is used to measure contractility both in untreated myocardial tissue and in tissue exposed to an inotropic agent. Clear differences are observed between conditions, suggesting that the proposed platform has significant potential to provide clinically relevant measurements of contractility.

Original languageEnglish
Article number2207498
Pages (from-to)e2207498
JournalAdvanced Science
Volume10
Issue number27
Early online date23 Jul 2023
DOIs
StatePublished - Sep 2023
Externally publishedYes

Bibliographical note

Funding Information:
M.Y. and M.H. contributed equally to this work. The authors are especially grateful to Dr. Offir Ertracht from the Cardiovascular Research Laboratory at the Galilee Medical Center, Nahariya for his assistance with the in vivo study, to Prof. Gil Markovich and Prof. Tal Dvir for their assistance and support, to Rafael Aginyan for his assistance with the magnetic gels, to Dr. George Levi for the TEM images, and Gal Balush for the artwork. B.M.M. acknowledges funding support from the Slezak Foundation, the Israel Science Foundation (ISF Grant No. 2248/19), and the Israel Ministry of Science and Technology (Grant No. 3–17351). H.Y. acknowledges funding support from the Science, Technology, and Innovation Commission of Shenzhen Municipality (Grant No. ZDSYS20210623092005017).

Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

  • afterload
  • cardiac in vitro models
  • force application on cells
  • magnetic gels
  • preload
  • Hydrogels
  • Magnetic Phenomena
  • Myocardial Contraction/physiology
  • Myocardium
  • Heart/physiology

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