Developing a next-generation gut-brain axis organ-on-chip

This multi-organ system will simulate the human body and provides an animal-free solution for modelling human diseases and pre-clinical drug development.

 

With our team of experts in the fields of organ-on-chip technology, organoids, bioengineering, virology, immunology and cell culturing, GUTVIBRATIONS will lead innovation in the fields of complex organ-on-chip technology for virology.

We’re recruiting!

Are you passionate about organ-on-chip (OoC) technology and are you looking to be a part of a driven team that will push OoC technology to the next level? Then check out our vacancies!

GUTVIBRATIONS will push next-generation organ-on-chip technology forward into the biomedical industry.

 

1. STACKS

STACKS - GUTVIBRATIONS is based on a 3D printed platform called STACKS established at the Technical University of Denmark. STACKS are simple to use, easy to fabricate and are a readily scalable and stackable system. It is a multilayer system consisting of 3D printed multiwell plates with each plate mimicking a different organ. A STACKS plate is very similar to Transwell® inserts. Unlike Transwell® inserts, STACKS have an opening onto which an extra cellular matrix (ECM) like layer can be cast, which provides the natural cellular microenvironment as found in vivo. The well plates can be stacked on top of each other creating a multi-organ system.

2. Biosilk

GUTVIBRATIONS will use Biosilk, a biomaterial made from recombinant spider silk protein. Biosilk is a biocompatible, biodegradable, and non-immunogenic biomaterial that can be functionalised with specific ECM proteins such as laminins and collagen. The spider silk protein is produced by recombinant expression in a bacterial system that makes it highly robust and reproducible. This is a significant improvement on traditionally used ECM layers such as Matrigel and collagen that are animal-derived and show lot-to-lot variability. Biosilk is also highly versatile and can be remodeled in different forms depending on the physiological segment that needs to be mimicked. In GUTVIBRATIONS, Biosilk will be used in two different forms - Biosilk nanomembrane (representing the basement membrane) and Biosilk (representing the underlying ECM). Both forms of Biosilk are provided by Biolamina AB and KTH Royal Institute of Technology.

3. Organoids

Together with the STACKS and Biosilk, gut and brain organoids will form the basis for the next-generation gut-brain axis organ-on-chip (Ooc). Gut organoids are derived from intestine-specific stem cells. Stem cells self -organise into 3D structures to form organoids. Brain organoids are brain-like 3D cultures derived from pluripotent stem cells and contain brain-specific cell types. The gut and brain organoids are provided by the Amsterdam University Medical Centers, UniQure and KU Leuven.

4. Media

STEMCELL Technologies (SC) will provide validated media for the formation and culture of human brain organoids. In addition to the different cell types found in the gut and brain organoids, these organs are supported by several other cell types with specific functions in vivo. For the brain layer, it is vital to include a Blood Brain Barrier (BBB) supported by brain associated cells such as pericytes, astrocytes, and microglia. Media for generating these different cell types from iPSCs will also be provided by SC. In GUTVIBRATIONS, specialised media will be developed by SC for each co-culture system. Each layer of the gut-brain axis organ-on-chip will be supplied with a different media, enabling straightforward integration.

5. Viruses

The brain-gut axis organ-on-chip provides a model to investigate important questions regarding the pathogenesis of viral diseases. The viruses that will be investigated within GUTVIBRATIONS are Enterovirus (EV), Human immunodeficiency virus (HIV) and Human norovirus (HuNoV) which all initiate infection in the gut and can result in neurological symptoms later on.

6. Treatment

The brain-gut axis organ-on-chip provides a system that can accurately simulate diseases caused by viruses, allowing for drugs to be tested against these specific diseases. Within GUTVIBRATIONS, the potential treatment of two different viral infections will be studied.

7. High throughput screening

To make the STACKS platform suitable for industrial applications, the STACKS will be scaled up to a 96-well format for high throughput screening. In addition, GUTVIBRATIONS will ensure that the 96-well format is compatible with pipetting and will adapt the plate format to a polystyrene base for high throughput manufacturing.

Multi organ system

The GUTVIBRATIONS team combines expertise in organ-on-chip technology, 3D printing, bioengineering, organoids and virology to develop the gut-brain axis organ-on-chip (OoC).

 

To build this multi-organ system, the gut-brain axis OoC is divided into separate parts also known as modules.

 

Each module simulates a different region or function along the gut-brain system and is developed and validated separately before being assembled into the complex gut-brain axis OoC. Every module is based on three layers – STACKS, Biosilk and human organoids.

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Team

Dasja

Dasja Pajkrt

Coordinator

Dasja co-coordinates the GUTVIBRATIONS project and is responsible for the coordination of the training and exploitation activities.

katja

Katja Wolthers

Coordinator

Katja co-coordinates the GUTVIBRATIONS project and is responsible for the coordination of the project management activities.

Adithya-Sridhar-2

Adithya Sridhar

Scientific Manager
Adithya is a senior scientist at the Amsterdam UMC. He is responsible for providing scientific and technical support.

Angelica

Angelica Reitsma

Project Manager
Angelica is the manager of GUTVIBRATIONS. She is responsible for the overall planning and execution of the project.

Dara-Satrio-gzw

Dara Satrio

Science Communications Officer
Dara is the Science Communications Officer of GUTVIBRATIONS