Enhanced differentiation of human embryonic stem cells towards definitive endoderm on ultrahigh aspect ratio nanopillars

Holzmann Rasmussen, C., Reynolds, P. , Petersen, D. R., Hansson, M., McMeeking, R. M., Dufva, M. and Gadegaard, N. (2015) Enhanced differentiation of human embryonic stem cells towards definitive endoderm on ultrahigh aspect ratio nanopillars. Advanced Functional Materials, 26(6), pp. 815-823. (doi:10.1002/adfm.201504204)

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Abstract

Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have highlighted that the properties of the physical environment, such as substrate stiffness, affect cellular behavior. Here, mass-produced, injection molded polycarbonate nanopillars are presented, where the surface mechanical properties, i.e., stiffness, can be controlled by the geometric design of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.0003). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of definitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure population compared to planar control. By contrast, further differentiation toward the pancreatic ­endoderm is less successful on “soft” pillars when compared to “stiff” pillars or control, indicating differential cues during the different stages of differentiation. To accompany the mechanical properties of the nanopillars, the concept of surface shear modulus is introduced to describe the characteristics of engineered elastic surfaces through micro or nanopatterning. This provides a framework whereby comparisons can be drawn between such materials and bulk elastomeric materials.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gadegaard, Professor Nikolaj and Reynolds, Dr Paul
Authors: Holzmann Rasmussen, C., Reynolds, P., Petersen, D. R., Hansson, M., McMeeking, R. M., Dufva, M., and Gadegaard, N.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Functional Materials
Publisher:Wiley
ISSN:1616-301X
ISSN (Online):1616-3028
Published Online:15 December 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Advanced Functional Materials 26(6): 815-823
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
470561DTC in cell and proteomic technologies (continuation)Jonathan CooperEngineering & Physical Sciences Research Council (EPSRC)EP/F500424/1ENG - BIOMEDICAL ENGINEERING