title: Shear stress with appropriate time-step and amplification enhances endothelial cell retention on vascular grafts.
abstract: Endothelial cells (ECs) are sensitive to changes in shear stress. The application of shear stress to ECs has been well documented to improve cell retention when placed into a haemodynamically active environment. However, the relationship between the time-step and amplification of shear stress on EC functions remains elusive. In the present study, human umbilical cord veins endothelial cells (HUVECs) were seeded on silk fibroin nanofibrous scaffolds and were preconditioned by shear stress at different time-steps and amplifications. It is shown that gradually increasing shear stress with appropriate time-steps and amplification could improve EC retention, yielding a complete endothelial-like monolayer both in vitro and in vivo. The mechanism of this improvement is mediated, at least in part, by an upregulation of integrin β1 and focal adhesion kinase (FAK) expression, which contributed to fibronectin (FN) assembly enhancement in ECs in response to the shear stress. A modest gradual increase in shear stress was essential to allow additional time for ECs to gradually acclimatize to the changing environment, with the goal of withstanding the physiological levels of shear stress. This study recognized that the time-steps and amplifications of shear stress could regulate EC tolerance to shear stress and the anti-thrombogenicity function of engineered vascular grafts via an extracellular cell matrix-specific, mechanosensitive signalling pathway and might prevent thrombus formation in vivo. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Gong
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jing
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Xili
authors.initials: X
authors.lastname: Ding
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.|National Research Centre for Rehabilitation Technical Aids, Beijing, People's Republic of China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
mesh_terms: D001807:Blood Vessel Prosthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular; D033081:Shear Strength; D013314:Stress, Mechanical; D054457:Tissue Scaffolds
keywords: amplification; endothelial cell; shear stress; silk fibroin vascular graft; time-step