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Thibault Krammer

Development of a microvascular network on a microfluidic chip for tissue reconstruction

Published on 10 December 2019
Thesis presented December 10, 2019

Organ-on-chips are biological environments created within a microfluidic chip. It reproduces the functions of a biological tissue or an organ. Organ-on-chips thus offer test platforms for new therapeutic that improve the effectiveness of treatments provided to patients. In the longer term, the development of healthy physiological tissues promises to be used as implants to replace or support failing organs.
However, reproductions of tissues are confronted with the difficulties of developing a perfusable vascular network. In vivo, the vascular network supplies the body's cells with oxygen and nutrients and plays a major role in maintaining organ homeostasis. One limitation or organs on a chip at the moment is the development of a vascular network. The created tissues containing a capillary network of a few microns are thin (< 500 µm) while for thicker tissues, the size of the vessels is greater than 100 µm in diameter, which does not represent a human tissue. The objective of this thesis is to build a network of blood capillaries with physiological dimensions integrated within a thick tissue construction.
An innovative vascularization technique has been developed, consisting of packing microspheres covered with endothelial cells in a microfluidic reservoir. The control of the size of the microspheres allow to control the dimension of the capillaries formed. The stimulation of endothelial cells within the structure promotes self-assembly into blood capillaries. This technique allows the rapid development of thick tissues as well as the control of the size and density of the developed capillaries. It also allows the encapsulation of several cell types which makes it compatible with the development of many tissues.
In order to carry out this technique, a device for the production of spherical microenvironments has been built. The stacking structure of microenvironments was studied in order to characterize the flows through the structure and apply controlled physical stimuli to cells. A microfluidic bioreactor-like system was manufactured and allowed the development of capillary networks within thick tissue construction.

3D Vascular Network, Microfluidic, Organ-on-chip, Tissue Engineering

On-line thesis.