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The handle

http://hdl.handle.net/1887/80612

holds various files of this Leiden University

dissertation.

Author: Mieremet, A.

Title: A multidirectional approach to optimize morphogenesis and barrier characteristics

of human skin equivalents

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A multidirectional approach to optimize morphogenesis and

barrier characteristics of human skin equivalents

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Dermatology of the Leiden University Medical Center (LUMC) and at the Division BioTherapeutics of the Leiden Academic Centre for Drug Research (LACDR), Leiden University (Leiden, The Netherlands). The research was financially supported by the Netherlands Organization for Scientific Research (NWO) domain Applied and Engineering Sciences (TTW) (project number 13151), which is partly funded by the Ministry of Economic Affairs and Climate Policy, and the Ministry of Education, Culture and Science.

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A multidirectional approach to optimize morphogenesis and

barrier characteristics of human skin equivalents

Proefschrift

Ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op donderdag 14 november 2019

klokke 11.15 uur

door

Arnout Mieremet

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Promotiecommissie:

Prof. dr. H. Irth, Leiden Academic Centre for Drug Research (LACDR) (Chairman) Prof. dr. A.P. IJzerman, Leiden Academic Centre for Drug Research (LACDR) (Secretary)

Prof. dr. M.H. Vermeer, Leiden University Medical Center (LUMC) Prof. dr. M. Schäfer-Korting, Free University Berlin

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Contents

Chapter 1 Introduction 7

Part I

Chapter 2 Recapitulation of native dermal tissue in a

full-thickness human skin model using human collagens 33 Chapter 3 Improved epidermal barrier formation in human skin

models by chitosan modulated dermal matrices

57

Part II

Chapter 4 Characterization of human skin equivalents developed at body’s core and surface temperatures

89 Chapter 5 Human skin equivalents cultured under hypoxia

display enhanced epidermal morphogenesis and lipid barrier formation

113 Chapter 6 Unravelling effects of relative humidity on lipid

barrier formation in human skin equivalents 139 Chapter 7 Shedding light on the effects of 1,25-dihydroxyvitamin

D3 on epidermal lipid barrier formation in three-dimensional human skin equivalents

165

Part III

Chapter 8 Contribution of palmitic acid to epidermal

morphogenesis and lipid barrier formation in human skin equivalents

193 Chapter 9 Multitargeted approach for the optimization of

morphogenesis and barrier formation in human skin equivalents

223

Chapter 10 Summary and perspectives 251

Chapter 11 Nederlandstalige samenvatting (Dutch Summary) 270

Curriculum Vitae 280

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