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bioRxiv · 10.1101/2025.06.02.656802

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

Nkansah, A.·Budhwani, A.·Grammer, N.·Ang, N.·Fairley, A.·Salazar, S. P.·Anand, A.·Yedalla, A. C.·Seidlits, S.·Allen, J.·Cosgriff-Hernandez, E.
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Abstract

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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/656802v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@41bfb9org.highwire.dtl.DTLVardef@921619org.highwire.dtl.DTLVardef@e8df4corg.highwire.dtl.DTLVardef@9c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Nkansah, A., Budhwani, A., Grammer, N., Ang, N., Fairley, A., Salazar, S. P., Anand, A., Yedalla, A. C., Seidlits, S., Allen, J., Cosgriff-Hernandez, E.. 2025-06-05. Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cel Adhesion to Bioactive Hydrogels. https://doi.org/10.1101/2025.06.02.656802

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