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In Vitro Model Integrating Substrate Stiffness and Flow to Study Endothelial Cell Responses
Published on: July 19, 2024
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Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cell Adhesion to Bioactive Hydrogels
Abbey Nkansah1, Aashee Budhwani1, Nicholas Grammer1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.
ACS Biomaterials Science & Engineering
|October 3, 2025
Summary
Biological sex impacts how endothelial cells interact with biomaterials, influencing device performance. Understanding these sex differences in integrin expression is crucial for designing better blood-contacting medical devices.
Area of Science:
- Biomaterials Science
- Cell Biology
- Cardiovascular Research
Background:
- Endothelialization is key for thromboresistance in blood-contacting devices.
- Current biomaterial designs often neglect sex-based differences in endothelial cell behavior.
- Integrin-mediated cell-material interactions are critical for endothelial function.
Purpose of the Study:
- To investigate sex differences in human coronary artery endothelial cell (HCEC) interactions with biomaterials.
- To elucidate the role of integrin-ligand interplay in sex-biased endothelial cell responses.
- To inform the design of sex-specific biomaterials for medical devices.
Main Methods:
- Characterized integrin expression in HCECs from age-matched male and female donors.
- Assessed HCEC adhesion and spreading on poly(ethylene glycol)-based hydrogels with collagen or gelatin.
- Correlated integrin expression profiles with observed cell behaviors on different substrate stiffnesses.
Main Results:
- Identified distinct sex-based integrin expression patterns in HCECs.
- Female HCECs exhibited higher expression of α2β1, α5β1, and αVβ3 integrins.
- Male HCECs showed higher α1β1 integrin expression.
- Female HCECs demonstrated greater attachment on stiff hydrogel substrates compared to male HCECs.
Conclusions:
- Sex-based differences in endothelial cell responses to bioactive hydrogels are mediated by integrin interactions.
- Biological sex is an important variable to consider in the design of blood-contacting biomaterials.
- Tailoring biomaterials based on sex can enhance thromboresistance and device efficacy.
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