Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars

Camilla Holzmann Rasmussen, Paul M. Reynolds, Dorthe Roenn Petersen, Mattias Hansson, Robert M. McMeeking, Martin Dufva, Nikolaj Gadegaard*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)
6 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)815-823
Number of pages9
JournalAdvanced Functional Materials
Volume26
Issue number6
Early online date15 Dec 2015
DOIs
Publication statusPublished - 9 Feb 2016

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stem cells
Stem cells
aspect ratio
Aspect ratio
polycarbonate
Stiffness
stiffness
Mechanical properties
mechanical properties
Medical problems
Polycarbonates
cues
polycarbonates
cells
Elastic moduli
therapy
induction
injection
shear
Substrates

Keywords

  • human embryonic stem cells
  • injection moulding
  • mechanotransduction
  • nanostructures

ASJC Scopus subject areas

  • Biomaterials
  • Electrochemistry
  • Condensed Matter Physics
  • Electronic, Optical and Magnetic Materials

Cite this

Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars. / Rasmussen, Camilla Holzmann; Reynolds, Paul M.; Petersen, Dorthe Roenn; Hansson, Mattias; McMeeking, Robert M.; Dufva, Martin; Gadegaard, Nikolaj.

In: Advanced Functional Materials, Vol. 26, No. 6, 09.02.2016, p. 815-823.

Research output: Contribution to journalArticle

Rasmussen, Camilla Holzmann ; Reynolds, Paul M. ; Petersen, Dorthe Roenn ; Hansson, Mattias ; McMeeking, Robert M. ; Dufva, Martin ; Gadegaard, Nikolaj. / Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars. In: Advanced Functional Materials. 2016 ; Vol. 26, No. 6. pp. 815-823.
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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.",
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