Periodic Reporting for period 3 - IMBIBE (Innovative technology solutions to explore effects of the microbiome on intestine and brain pathophysiology)
Berichtszeitraum: 2020-10-01 bis 2022-03-31
Although our ultimate goal is the connected model of gut-brain and microbiome, the individual modules are already garnering interest as test models for a variety of laboratories worldwide, in Korea, Finland, Wales and Ireland so far. Many groups are keen to test bacterial products or mimic diseases such as Crohn’s disease to determine how they might use microbes or their derivatives to protect against or even reverse deleterious effects on the gut (and brain). In the short term, this project has the potential to dramatically change how such things are studied in vitro. In the long term, our work will contribute towards the understanding of diseases related to microbial imbalances in the human body.
The tunable properties of PEDOT:PSS and the in situ fabrication process we adopted allowed us to fine-tune the electrical, mechanical and biochemical properties of the scaffolds. This allows really interesting tissue engineering applications, where cell growth and fate can be determined by changing the combination of these stimuli in vitro.
Our new generation Tubistor platforms allows us to mimic luminal architecture of the human gastrointestinal tract. The new version of the device supports maintenance and monitoring of a biological model of the human gut epithelium for 26 days. Our approach to gradually build the tri-culture intestinal cell model by firstly culturing fibroblasts in the porous bulk compartment of the hollow scaffolds and later injecting intestinal epithelial cells to line the lumen lining and form the epithelial layer anchoring on the basal lamina was proven successful for the reconstruction of the desired tissue microenvironment. The configuration/design of our device enables real-time, non-invasive monitoring of cell activity and tissue formation on the scaffolds, as evidenced by modulation of their electrical properties. In addition, the configuration of our bioelectronic platform enables bi-modal operation of the device – both as electrode and as a transistor – thereby providing us with more electrical readouts, analysis of which reveals valuable information for the biological model in real time, cross-validated with optical analysis. The unique integration of in-line sensing components in a 3D intestinal system achieved with our system highlights the potential of this technology for building more advanced experimental models of the human gut as tools for studying disease pathology, host-pathogen and host-microbiome interactions, as well as for identifying novel therapeutic targets.