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Published on: November 20, 2015
Cyclic stretch inhibits cell invasion in 3D scaffolds
Rozanne Mungai1, Juanyong Li1, Jamie Baines1
1Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01605.
Biorxiv : the Preprint Server for Biology
|June 29, 2026
Summary
Cyclic stretch inhibits host cell invasion into tissue-engineered heart valves (TEHVs), contrary to expectations. This finding suggests the dynamic valve environment may limit TEHV repopulation and impacts understanding of cell invasion in other tissues.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Tissue Engineering
Background:
- Clinically viable tissue-engineered heart valves (TEHVs) face challenges with host cell infiltration.
- The role of the dynamic hemodynamic environment, specifically cyclic stretch, in cell invasion within 3D scaffolds is largely unexplored.
- Previous studies suggested uniaxial constraint enhances invasion, leading to the hypothesis that cyclic stretch would promote it.
Purpose of the Study:
- To investigate the effects of uniaxial cyclic stretch on cell invasion and proliferation in 3D collagen hydrogels relevant to TEHVs.
- To compare the responses of different cell types (smooth muscle cells, valvular interstitial cells, dermal fibroblasts) to cyclic stretch.
- To elucidate the underlying mechanisms, including cell tension and myosin IIA activity.
Main Methods:
- Multicellular spheroids were embedded in collagen hydrogels and subjected to uniaxial cyclic stretch (3-10%, 1 Hz) for two days.
- Cell invasion into the extracellular matrix was quantified using custom image processing.
- Mechanisms were assessed via gel compaction assays, myosin IIA inhibition, and Ki67 immunostaining for proliferation.
Main Results:
- Contrary to the hypothesis, cyclic stretch significantly inhibited cell invasion across all tested cell types (>50% reduction for SMCs/fibroblasts, up to 99% for VICs).
- Invasion suppression was inversely correlated with cell contractility, suggesting a role for cell-generated tension.
- Myosin IIA inhibition partially rescued invasion, and stretched spheroids showed reduced cell proliferation.
Conclusions:
- Actomyosin-mediated mechanotransduction suppresses cell invasion under cyclic stretch, impacting TEHV host-cell repopulation.
- The dynamic mechanical environment of heart valves may limit their functional integration.
- Findings offer broader insights into cyclic stretch regulation of 3D cell invasion in mechanically active tissues, with implications for wound healing and metastasis.
