Tuning Surface Chemistry Impacts on Cardiac Endothelial and Smooth Muscle Cell Development

Abstract

Cardiovascular diseases (CVDs) are the leading causes of death worldwide, with approx. Twenty million deaths in 2021. Cardiovascular implants are among the most used biomaterials in the clinical world. However, poor endothelialisation and rapid thrombosis remains a challenge. Simple chemical surface modification techniques can be used to steer biological interactions without affecting the bioimplants' overall bulk characteristics such as radiopacity and flexibility. Although silanes are well studied for protein and cell interactions, the methodical investigation of cardiac endothelial cell (EC) alongside smooth muscle cell (SMC) to mimic natural arterial environments has been limited. In this study, these cells have been investigated on surfaces functionalized with methyl, amine, thiol, methacrylate, and fluorine organosilane groups. Cardiac EC and SMC growth was investigated with metabolic activity, time lapse imaging, and immunofluorescent staining techniques. The results demonstrated that the surfaces tested are able to selectively regulate the viability and growth of the cells. Aminosilane modified surfaces displayed 2-fold higher metabolic activity with HUVEC and 2-fold less metabolic activity with HCASMC cell lines, compared to tissue culture plastic controls. The amino-modification outperformed all other chemistries tested in terms of ability to promote the proliferation of ECs, while importantly reducing the activity of SMCs. This report demonstrates that aminosilane modified surfaces have the potential to be utilized in novel cardiovascular implants, which could improve biological integration in the short and possibly longer-term. The findings of this study suggest that specific chemical modifications of the surface can enhance endothelial cell activity while minimizing the proliferation of smooth muscle cells, which are often associated with thrombosis. This highlights the potential of carefully engineered surface chemistries to improve the clinical outcomes of cardiovascular implants.