Journal
BIOMATERIALS
Volume 34, Issue 12, Pages 2928-2937Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.01.017
Keywords
Endothelium; Nanotopography; Micropatteming; Vascular graft; Monocyte; Cell morphology
Funding
- National Heart, Lung and Blood Institute [U01HL100397, RC2HL103400, 1K12HL087746]
- BioX Program of Stanford University [IIP-53]
- National Science Foundation [EFRI-MIKS 1136790]
- National Institutes of Health [HL098688]
- National Science Foundation
- EFRI-MIKS [1136790]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0754060] Funding Source: National Science Foundation
- Directorate For Engineering
- Emerging Frontiers & Multidisciplinary Activities [1136790] Funding Source: National Science Foundation
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Microscale and nanoscale structures can spatially pattern endothelial cells (ECs) into parallel-aligned organization, mimicking their cellular alignment in blood vessels exposed to laminar shear stress. However, the effects of spatial patterning on the function and global transcriptome of ECs are incompletely characterized. We used both parallel-aligned micropatterned and nanopatterned biomaterials to evaluate the effects of spatial patterning on the phenotype of ECs, based on gene expression profiling, functional characterization of monocyte adhesion, and quantification of cellular morphology. We demonstrate that both micropatterned and aligned nanofibrillar biomaterials could effectively guide EC organization along the direction of the micropatterned channels or nanofibrils, respectively. The ability of ECs to sense spatial patterning cues were abrogated in the presence of cytoskeletal disruption agents. Moreover, both micropatterned and aligned nanofibrillar substrates promoted an athero-resistant EC phenotype by reducing endothelial adhesiveness for monocytes and platelets, as well as by down-regulating the expression of adhesion proteins and chemokines. We further found that micropatterned ECs have a transcriptional signature that is unique from non-patterned ECs, as well as from ECs aligned by shear stress. These findings highlight the importance of spatial patterning cues in guiding EC organization and function, which may have clinical relevance in the development of vascular grafts that promote patency. (C) 2013 Elsevier Ltd. All rights reserved.
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