Dynamic Skin-on-a-Chip Models: A Novel Platform for Investigating the Mechanisms of Skin Tissue Formation

Katharina Kaiser

Research output: ThesisPh.D. thesis

Abstract

Since their first development in the 1980s, tissue-engineered skin equivalents have gained increasingly more attention with the aim to replace animal models for pharmaceutic and cosmetic efficacy and toxicity studies. From the first constructs consisting of simple homogeneous cell cultures, present skin equivalents have become increasingly complex incorporating multiple cell sources, different native scaffolds, and chemical and physical stimulation. However, the current models still lack the mechanical stability found in native skin, mainly due to missing mechanical and biophysical cues.
In this work, a novel skin-on-a-chip platform was designed to permit dynamic perfusion and mechanical stimulation during the cultivation of skin equivalents, that in the future could serve as a test system for pharmaceutical research. The platform is composed of PDMS and commercial PETE membranes, making it an affordable and easy system. Subsequent characterization of the skin equivalents revealed changes in gene and protein expression due to the dynamic environment.
It was demonstrated that the skin equivalents reflected the morphology of native skin. Mechanical compression resulted in a thinner epidermal thickness compared to transwell cultures and static skin-on-a-chip cultures.
The skin equivalents were analyzed using immunohistochemistry to determine changes in the expression of proteins related to differentiation and tissue integrity. Skin equivalents grown with perfusion displayed higher protein expression of Keratin 10 and Keratin 14. Compressive stimulation resulted in an increase of Desmoplakin 1&2 and Claudin-1, which indicates increases in desmosomes and tight junctions, postulating better tissue integrity. Changes in gene expression were detected using bulk RNA sequencing and a complex interplay in gene regulation related to proliferation and tissue homeostasis was observed.

In conclusion, this work presents a biomimetic skin equivalent with morphology similar to that of human skin. In the future, the system could provide a test system for drug and perfusion studies. It has the potential to become a tool to study the physiological and pathological aspects of skin.
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Brewer, Jonathan, Principal supervisor
Date of defence13. Nov 2023
Publisher
DOIs
Publication statusPublished - 4. Nov 2023

Note re. dissertation

Print copy of the thesis is restricted to reference use in the Library. 

Keywords

  • skin-on-a-chip
  • artificial skin
  • microfluidics
  • organ-on-a-chip

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