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June 5th, 2025
Version: 2
The University of Texas at Austin
bioengineering
biorxiv

Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cell Adhesion to Bioactive Hydrogels

Nkansah, A.Open in Google Scholar•Budhwani, A.Open in Google Scholar•Grammer, N.Open in Google Scholar•Ang, N.Open in Google Scholar•Fairley, A.Open in Google Scholar•Salazar, S. P.Open in Google Scholar•Anand, A.Open in Google Scholar•Yedalla, A. C.Open in Google Scholar•Seidlits, S.Open in Google Scholar•Allen, J.Open in Google Scholaret al.

Endothelialization promotes thromboresistance in blood-contacting devices, but biomaterial designs often overlook sex differences in endothelialization processes. In this study, we elucidated sex differences in endothelial cell-material interactions through investigation of the integrin-ligand interplay with biomaterial substrates and the corollary effects on cell adhesion and spreading. First, integrin expression of human coronary artery endothelial cells (HCAECs) was characterized for age-matched donors (3 male, 3 female). Sex-based differences in integrin expression were identified, with notably higher 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells and higher 1{beta}1 expression in male cells. On polyethylene glycol (PEG)-based hydrogel incorporating collagen or gelatin, female cells showed increased attachment on stiff substrates as compared to male HCAECs, likely driven by increased 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells. Collectively, these results demonstrate sex-biased endothelial cell responses to bioactive hydrogels mediated by integrin interactions and highlight the importance of incorporating biological sex as a design variable in the development of blood-contacting biomaterials.

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