University of Groningen
Influences of Complex Topography and Biochemistry on Mesenchymal Stem Cell
Differentiation
Yang, Liangliang
DOI:10.33612/diss.146104615
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Publication date: 2020
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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
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
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
Promotor
Dr. P. van Rijn
Co-Promotor
Dr. T.G. van Kooten
Assessment Committee
Prof. R.A. Bank
Prof. P.R. Onck
Paranymphs:
Torben A. B. van der Boon
Valentina Vignali
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
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