3D bio-printing inside a hydrogel
(Nanowerk News) Scientists from across UCL, Great Ormond Street Hospital and University of Padova have shown how 3D printing can be achieved inside ‘mini organs’ grown in hydrogels, which could help better understand how cancer spreads through different tissues.
This new technique could help control the shape and activity of mini organs, and even force tissue to grow into ‘mushrooms’. The researchers hope this will allow the team to produce realistic models of organs and diseases, and study cells and organs more accurately.
Organoid science is a very promising research area at the Zayed Center for Research (a partnership between the UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital). This involves creating micro versions of organs such as the stomach, intestines and lungs.
However, tissues almost always grow in an uncontrolled manner and do not represent the complex structures of natural organs. This is very important because the shape and structure of an organ is just as important as its cellular makeup.
New research, published in Nature Communications (“Living hydrogel-in-hydrogel bioprinting for the guidance and control of organoids and organotypic cultures”), demonstrating for the first time how scientists can create solid structures in pre-existing gels to solidify specific patterns in real time, guiding organoids growing in the gel into specific structures using light from a high-specification microscope. This means that every cell in a growing mini organ or an entire organoid will grow in a specific and precise way.
For example, to study how cancer spreads through tissues of different hardness and densities, the team built a hardened gel cage around cancer cells and monitored how their movement changed depending on the density of their environment – important for understanding cancer spread.
By creating a better disease model, future studies will be more reliable and have higher quality results. Researchers hope this will eventually lead to a reduction in animal studies.
The team now plans to use the technique to recreate and study what happens to organ function when it doesn’t grow properly – for example in the many malformations that develop in the early stages of pregnancy.
The work could also lead to medicine through the delivery of biologically accurate ‘patches’ on living organs.
Study co-author, Dr Giovanni Giobbe (UCL Great Ormond Street of Child Health), said: “It’s been amazing to see these precise structures starting to form before our eyes due to tiny but painstaking adjustments to the polymer gel.
“We are excited to see where this can take us in the understanding of human disease and one day, treatment.”
To explore the use of the ‘printing’ technique, the team applied the method to a number of different situations.
For example, to study neurons, organoid studies have traditionally created disorganized assemblages of neurons that are impossible to isolate and study. However, the technique allowed the team to create hardened gel “rails” for neurons to grow, much like the pathways of an Olympic swimming pool.
Meanwhile, to ensure that the microscopic gut was rendered in the same shape as the ‘real’ developing gut, the team created complex hydrogel templates that guided the organoids into shapes that mimicked the complex structures of the developing gut called ‘crypts’ and ‘villi’.
Similarly, scientists can create hydrogel patterns to encourage lung cells to branch, just as they did in real lungs.
Professor Paolo De Coppi (UCL Great Ormond Street Institute of Child Health, pediatric surgeon at GOSH, and co-lead on tissue and engineering and regenerative medicine themes at NIHR GOSH BRC), said: “This work is an excellent example of how we can bring together international interdisciplinary teams to enhance research and benefit patients.
“The team at GOSH and UCL specializing in organoid research in the UK, working with an Italian team specializing in the design and application of gel printing, is what made this extraordinary and beautiful research come to fruition. This will have implications for laboratory-based research to increase our understanding of the disease but may also lead to inpatient use and treatment.”
The next step for this work is to study these controlled, shaped, and directed miniature organs to better understand how they can mimic real organs and conditions inside the body.
Dr Anna Uriuolo (University of Padova and head of the Neuromuscular Engineering Laboratory at the Institute of Pediatric Research) said: “This work is an example of the exploding advances in multidisciplinary approaches in biomedical research. The ability to reproduce organ models in the laboratory and the development of technologies that help scientists to recapitulate healthy and diseased tissue and organ complexity in stool are the start of how translational medicine will change in the future.”
