Bioprinting the gut microbiome for personalised medicine

Increasing evidence points to the gut microbiome determining an individual's health, with a change in the microbiome leading to diseases. New studies have shown the importance of the gut affecting the performance of other organs, such as the brain, kidney and bones, referred to as, for example, gut-brain axis. Moreover, the composition of the microbiome can interfere with drug efficacy, as recent evidence highlights depletion of drug by bacterial strains commonly found in the gut.

Thus, the gut microbiome is a key player in both determining one's health and response to therapeutics. The project proposes to leverage bioprinting to develop more sustainable tissue engineered models of the gut that factors in the microbiome. Such microbiome-inclusive gut models will be a significant advancement over contemporary gut tissue models.

Bioprinting is an emerging technology in the field of tissue engineering that utilises additive manufacturing (AM) tools to develop more reproducible tissue models. AM encompasses a range of technologies that produce products in additive manner. It also offers digital precision, ability to design complex and bespoke structures, and, and can be integrated with other digital tools.

AM tools widely used for bioprinting are extrusion-based techniques that require no or low-heat (< 40c) to process materials. These subsets of AM are ideal since they allow a range of tissue-relevant polymers and natural cells to be processed without damaging either material. Extrusion-based techniques are equipped with a multi-nozzle system that affords the user to develop multi-layered tissues, which are representative of natural tissue.

Furthermore, as a digitalised tool, AM can be integrated with imaging modalities to print precise replicas of an individual's tissue, hence affording personalised grafts to be developed.

The project will exploit the advantages of bioprinters to develop gut tissue models that include the microbiome. Contemporary consensus is that three-dimensional (3D) tissue models are more representative than current 2D models. The process takes advantage of the digital precision afforded by bioprinting, as well as its ability to design complex and multi-layered tissue models.

Both these features allow for reproducible bespoke models to be developed that will be an advancement on current tissue engineering approaches. Enhanced control over tissue size and architecture could ultimately yield artificial organs to be used for drug screening or eventual organ replacement. Of great importance, bioprinting has the potential to diminish the need for animal models, leading to more sustainable research, as well as reduce the waiting times for gut transplants.

Aspects of the project will involve:

- Develop a microbiome-inclusive gut tissue model using bioprinting. Explore materials that are compatible for both bioprinting and microbes - Investigate pre-bioprinting process that will maximise cell viability, such as microbe-encapsulating methods

- Exploit the printer's multi-nozzle compatibilities to advance gut tissue engineering and develop multi-layered tissues - Perform extensive characterisation techniques to understand the ideal printability characteristics

- Compare the performance of the bioprinted tissue models to traditional gut tissue models for high-throughput screening of drugs. In addition, assess whether the inclusion of the microbiome to the gut model will produce more representative drug performance. - Replicate different gut disease states using bioprinting

- Establish a strategy for extending the bioprinting pipeline beyond bioprinting. The goal will be to develop an automated, high-throughput system with bioprinting being a key component