Decellularized Extracellular Matrix and Polyurethane Vascular Grafts Have Positive Effects on the Inflammatory and Pro-Thrombotic State of Aged Endothelial Cells

Abstract

In vitro assessment of small-diameter synthetic vascular grafts usually uses standard cell culture conditions with early-passage cells. However, these conduits are mainly implanted in elderly patients and are subject to complex cellular interactions influenced by age and inflammation. Understanding these factors is central to the development of vascular grafts tailored to the specific needs of patients. In this study, the effects of aged endothelial cells subjected to pro- and anti-inflammatory agents and cultivated on a newly developed biodegradable electrospun thermoplastic polyurethane/poly(urethane-urea) blend (TPU/TPUU), on clinically available expanded polytetrafluorethylene (ePTFE), and on decellularized extracellular matrix (dECM) grafts were investigated. Young and aged endothelial cells were exposed to pro- and anti-inflammatory agents and characterized by morphology, migration capacity, and gene expression. In addition, the cells were seeded onto the various graft materials and examined microscopically alongside gene expression analyses. When exposed to pro-inflammatory cytokines, young and aged cells demonstrated signs of endothelial activation. Cells seeded on ePTFE showed reduced attachment and increased expression of pro-inflammatory genes compared with the other materials. dECM and TPU/TPUU substrates provided better support for endothelialization with aged cells under inflammatory conditions compared with ePTFE. Moreover, TPU/TPUU showed positive effects on reducing pro-thrombotic and pro-inflammatory gene expression in endothelial cells. Our results thus emphasize the importance of developing new synthetic graft materials as an alternative for clinically used ePTFE.