How 3D ‘bio-printing’ can shape mini-organs

A particularly promising area of research at the Zayed Centre for Research (a partnership between Great Ormond Street Hospital (GOSH), GOSH Charity and University College London Great Ormond Street Institute of Child Health (UCL GOS ICH)) is organoid science – the creation of micro-versions of organs like the stomach, the intestines and the lungs. But this tissue almost always grows in an uncontrolled way and doesn’t represent the complex structure of naturally occurring organs. This is particularly important as an organ’s shape and structure is as crucial as its cellular make up – in the stomach, or lungs and heart, for example.

This new research shows, how scientists can create solid structures within a pre-existing gel to solidify specific patterns in real time, guiding organoids growing in the gel into a particular structure by using light from a high-specification microscope. This means that any cell in the growing mini-organ or entire organoids will grow in a specific and precise way.

The paper, published in Nature Communications, shows how the team hope to recreate and study what happens to an organ’s function when it doesn’t grow correctly – for example in many malformations that develop in the early stages of pregnancy.

The team hope this research will create better models of disease which means that their studies are more reliable, the results are of better quality and the need for animal research is one day reduced. The work could also lead to treatment through the delivery of biologically accurate ‘patches’ in living organs.

Ordered cells

To study microscopic brain cells called neurons, organoid research would traditionally create disordered bundles of neurons that are impossible to isolate and study. This technique allows the team to create hardened gel ‘rails’ for the neurons to grow along, like the lanes of an Olympic pool.

Defined shapes

To create microscopic intestines with the same shape as ‘real’ developing intestines, the team created a complex hydrogel mould that guided organoids into shapes that mimic the complex structures of a developing intestine called ‘crypts’ and ‘villi’.

Creating branches

Scientists were able to pattern a hydrogel to encourage lung cells to create branches, like they do in ‘real’ lung.

Cancer spread

To study how cancer travels through tissue of different hardness and density, the team created hardened gel cages around cancer cells and monitored how the cancer cells movement changes depending on the density of its surroundings – this is important for understanding the spread of cancer.

Next steps for this work will be to study these controlled, moulded and directed mini-organs to better understand how they can mimic real organs and conditions in the body.

This work was funded by 2017 STARS-WiC grant of University of Padova, Progetti di Eccellenza CaRiPaRo, TWINING of University of Padova, Oak Foundation Award, AFM Telethon , ‘Consorzio per la Ricerca Sanitaria’ (CORIS) of the Veneto Region, Italy (LifeLab Program), European Research European Research Council (ERC, ReprOids) to N.E., and the STARS Starting Grant 2017 of University of Padova and IRP Consolidator Grant to A.U., NIHR GOSH Biomedical Research Centre and GOSH Children’s Charity