Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 7, Issue 8, Pages 4525-4532Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b00554
Keywords
nanotopography; substrate stiffness; endothelial cells; cytokines; chemokines
Funding
- Department of Bioengineering at the University of Washington
- American Heart Assocation [13SDG14560076]
- National Institutes of Health [R21AR064395]
- National Research Foundation - Ministry of Education, Science and Technology, Republic of Korea [2011-0014527]
- National Research Foundation of Korea [2011-0014527] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Endothelial physiology is regulated not only by humoral factors, but also by mechanical factors such as fluid shear stress and the underlying cellular matrix microenvironment. The purpose of the present study was to examine the effects of matrix topographical cues on the endothelial secretion of cytokines/chemokines in vitro. Human endothelial cells were cultured on nanopatterned polymeric substrates with different ratios of ridge to groove widths (1:1, 1:2, and 1:5) and with different stiffnesses (6.7 MPa and 2.5 GPa) in the presence and absence of 1.0 ng/mL TNF-a. The levels of cytokines/chemokines secreted into the conditioned media were analyzed with a multiplexed bead-based sandwich immunoassay. Of the nanopatterns tested, the 1:1 and 1:2 type patterns were found to induce the greatest degree of endothelial cell elongation and directional alignment. The 1:2 type nanopatterns lowered the secretion of inflammatory cytokines such as IL-1 beta, IL-3, and MCP-1, compared to unpatterned substrates. Additionally, of the two polymers tested, it was found that the stiffer substrate resulted in significant decreases in the secretion of IL-3 and MCP-1. These results suggest that substrates with specific extracellular nanotopographical cues or stiffnesses may provide anti-atherogenic effects like those seen with laminar shear stresses by suppressing the endothelial secretion of cytokines and chemokines involved in vascular inflammation and remodeling.
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