A Dynamic Gradient Stiffness Material Platform to Manipulate Cardiac Fibroblasts' Spatio-Temporal Behavior
Date
2024-04-05
Journal Title
Journal ISSN
Volume Title
Publisher
Advanced Functional Materials
Abstract
After myocardial infarction, there exists a spatiotemporal variation of cardiac tissue stiffness across the infarcted border region outward to remote regions, influencing adverse remodeling and cardiac fibrosis, and this stiffness gradient changes over time. Here, a platform with dynamic, tunable, and reversible gradient stiffness can recapitulate in vitro the time-dependent stiffness range across the infarction border that occurs as part of the remodeling process is presented. This platform enables the observation of time-dependent interaction between cardiac fibroblasts and their mechanical microenvironment in a spatiotemporal manner. Specifically, the competition and cooperation of a chemical cue (antifibrotic drug) and mechanical cue (gradient softening) in tandem to attenuate the fibrotic responses of cardiac fibroblasts is examined. Applying a combined intervention showed either additive or antagonistic effects on fibrosis-related gene regulation compared to separate interventions of drug or softening. This work reveals the spatiotemporal variation of fibrotic response in cardiac fibroblasts as well as the complexity of antifibrotic drug dosing with stiffness changes and their combinatory effect on cardiac fibroblasts. This platform provides a unique in vitro tool to study disease progression mechanisms in a more clinically relevant microenvironment and also serves as a cost-effective model for potential therapeutic screening.
Description
This is the peer reviewed version of the following article: Z. Cao, A. T. Clark, A. Vite, E. A. Corbin, A Dynamic Gradient Stiffness Material Platform to Manipulate Cardiac Fibroblasts' Spatio-Temporal Behavior. Adv. Funct. Mater. 2024, 2402808. https://doi.org/10.1002/adfm.202402808, which has been published in final form at https://doi.org/10.1002/adfm.202402808. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. © 2024 Wiley-VCH GmbH. This article will be embargoed until 04/05/2025.
Keywords
cardiac fibroblasts, gradient stiffness, magnetorheological elastomers, mechanobiology, spatio-temporal analysis
Citation
Z. Cao, A. T. Clark, A. Vite, E. A. Corbin, A Dynamic Gradient Stiffness Material Platform to Manipulate Cardiac Fibroblasts' Spatio-Temporal Behavior. Adv. Funct. Mater. 2024, 2402808. https://doi.org/10.1002/adfm.202402808