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University of Groningen Influences of Complex Topography and Biochemistry on Mesenchymal Stem Cell Differentiation Yang, Liangliang

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University of Groningen

Influences of Complex Topography and Biochemistry on Mesenchymal Stem Cell

Differentiation

Yang, Liangliang

DOI:

10.33612/diss.146104615

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Yang, L. (2020). Influences of Complex Topography and Biochemistry on Mesenchymal Stem Cell Differentiation. University of Groningen. https://doi.org/10.33612/diss.146104615

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Influences of Complex Topography

and Biochemistry on Mesenchymal

Stem Cell Differentiation

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Influences of Complex Topography and Biochemistry on Mesenchymal Stem Cell

Differentiation

By Liangliang Yang

University Medical Center Groningen, University of Groningen

Groningen, The Netherlands

Copyright © 2020 by Liangliang Yang

Printed by Ridderprint BV

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Influences of Complex Topography

and Biochemistry on Mesenchymal

Stem Cell Differentiation

PhD thesis

to obtain the degree of PhD at the

University of Groningen

on the authority of the

Rector Magnificus Prof. C. Wijmenga

and in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Monday 7 December 2020, at 11.00 hours

by

Liangliang Yang

born on 29 June 1988

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Promotor

Dr. P. van Rijn

Co-Promotor

Dr. T.G. van Kooten

Assessment Committee

Prof. R.A. Bank

Prof. P.R. Onck

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Paranymphs:

Torben A. B. van der Boon

Valentina Vignali

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Table of Contents

Chapter 1 General Introduction and Aim of this Thesis 1

1.1 Cells and their microenvironment 2

1.2 Cell sense the materials 3

1.3 Cells interact with biomaterials 3

1.4 Osteogenesis and neurogenesis of stem cells in clinical applications 4

1.5 Aim of this thesis 4

1.6 Outline of this thesis 5

1.7 References 6

Chapter 2 High-throughput Methods in the Discovery and Study of Biomaterials and Materiobiology 11

2.1 Introduction 12

2.2 Physicochemical influences on macroscopic cell behaviors 12

2.3 Physicochemical influences on stem cell differentiation 18

2.4 Limitations of gradient based high-throughput systems 23

2.5 References 24

Chapter 3 Topography induced stiffness alteration of stem cells influences osteogenic differentiation 31 3.1 Introduction 33 3.2 Methods 34 3.3 Results 36 3.4 Discussion 45 3.5 Conclusions 47 3.6 References 48

Chapter 4 Decoupling amplitude and wavelength of anisotropic topography and the influence on osteogenic differentiation of stem cells using a high-throughput screening approach 51

4.1 Introduction 53

4.2 Methods 54

4.3 Results and Discussion 55

4.4 Conclusion 61

4.5 References 63

Chapter 5

High-throughput screening and hierarchical topography-mediated neural differentiation of mesenchymal stem cells 67

5.1 Introduction 69 5.2 Methods 70 5.3 Results 72 5.4 Discussion 82 5.5 Conclusion 84 5.6 References 85

Chapter 6

Biomimetic multiscale hierarchical topography enhances osteogenic differentiation of human mesenchymal stem cells 87

6.1 Introduction 89 6.2 Methods 90 6.3 Results 92 6.4 Discussion 100 6.5 Conclusion 102 6.6 References 103

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Chapter 7 Synergistic effect of cell-derived extracellular matrix and topography on osteogenesis

of mesenchymal stem cells 107

7.1 Introduction 109 7.2 Methods 110 7.3 Results 112 7.4 Discussion 122 7.5 Conclusion 123 7.6 References 125

Chapter 8 General Discussion & Future Perspective 129

8.1 Discussion & Future plans 130

8.2 References 133 Summary 135 Samenvatting 139 Publications 143 Acknowledgements 145

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