Membrane based dynamic 3D tissue engineering

  • Dynamisches 3D-Tissue Engineering mit Membranen

Lohaus, Suzana; Wessling, Matthias (Thesis advisor); Steinseifer, Ulrich (Thesis advisor)

Aachen : RWTH Aachen University (2022)
Book, Dissertation / PhD Thesis

In: Aachener Verfahrenstechnik series - AVT.CVT - chemical process engineering 29
Page(s)/Article-Nr.: 1 Online-Ressource : Illustrationen

Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2022

Abstract

Membranes are used in numerous medical applications. They are an essential part of life-saving treatments, such as artificial organs, regenerative medicine, drug delivery or the production of biopharmaceuticals. Even though their applications are versatile, there are still major challenges that membrane technology must overcome. For once, the exerted influence of transport properties on the membrane interface is rather limited as mostly hollow fibers and flat sheet membrane geometries dominate the membrane market. This results in dead zones, deposits on the membrane, and reduced mass transport, reducing the membranes' longevity. In addition to that, membrane materials are often polymer-based, which impedes integration with biological systems, especially when blood contact is involved. Synthetic membrane materials therefore usually require extensive functionalization to make them useful for biological systems. Finally, membranes that are used in bioreactor applications, such as stem cell and long-term cultivation or cell retention for biopharmaceutical production, typically require a very high implementation effort because of being complex in handling and process control. This thesis addresses the further development of membrane geometries towards 3D membrane architectures, their material improvement for medical applications, particularly the improvement of blood compatibility, and most recently, the development of a temperature-responsive membrane bioreactor for the production of cellular tissue. This thesis proposes a unique membrane manufacturing process for the production of hierarchically porous polymeric 3D membranes by applying conventional non-solvent induced phase separation. Through the use of additive manufacturing, membranes with tailored geometries can now be produced, opening up the possibility of rethinking membrane and module design away from standard hollow fiber and flat sheet membranes. Moreover, this thesis presents a successful coating of an inert membrane surface with endothelial cells, which is a first important step towards long-term improvements of synthetic materials. Finally, this work demonstrates the development of a unique membrane bioreactor where temperature-responsive polymers lead to the non-invasive harvesting of interconnected cell tissues. Furthermore, integrating these polymers with a hollow fiber bioreactor enables the long-term cultivation of cells in a robust, reproducible and scalable cell cultivation system.

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