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GelMA hydrogel dual photo-crosslinking to dynamically modulate ECM stiffness
Josephina J H M Smits1, Atze van der Pol1,2, Marie José Goumans3
1Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
Frontiers in Bioengineering and Biotechnology
|July 5, 2024
Summary
Cellular memory of past mechanical environments, specifically extracellular matrix stiffness, significantly impacts cardiac fibroblast behavior and gene expression. This finding is crucial for understanding tissue remodeling after myocardial infarction.
Area of Science:
- Biomaterials Science
- Cellular Mechanobiology
- Tissue Engineering
Background:
- The extracellular matrix (ECM) stiffness dynamically influences cell behavior, particularly cardiac fibroblasts (cFbs) crucial for remodeling after myocardial infarction (MI).
- Understanding how dynamic changes in ECM stiffness affect cFb activation and ECM production is vital for regenerative medicine and disease modeling.
Purpose of the Study:
- To investigate the impact of dynamic substrate stiffness changes on cardiac fibroblast activation and ECM production.
- To elucidate the role of mechanical history in cellular responses to engineered microenvironments.
Main Methods:
- Development of a two-step photocrosslinking GelMA hydrogel system to dynamically alter substrate stiffness.
- Utilizing a TGF-β inhibitor to induce a quiescent state in cFbs for controlled observation of mechanical responses.
- Assessing cFb activation and ECM-related gene expression in response to varied substrate stiffness histories.
Main Results:
- Substrate mechanical history significantly influences cFb activation and ECM gene expression.
- Cells pre-conditioned on soft substrates exhibited reduced activation upon subsequent stiffening compared to cells directly exposed to stiff substrates.
- Demonstrated a 'cellular memory' effect where past mechanical environment dictates current cellular behavior.
Conclusions:
- Dynamic changes in ECM stiffness, and the mechanical history of the cellular environment, are critical regulators of cardiac fibroblast behavior.
- These findings provide new insights into mechanotransduction and have implications for developing therapies for post-MI cardiac remodeling and fibrosis.
