A 3D bionic printer structure for academic and industrial collaborations has been set up at Semmelweis University, which is now available in the online Core Facility system. The research facility at the 1st Department of Pathology and Experimental Cancer Research has a 3D bionic printer using living cells, a tissue breeder and an animal house as well. It can not only support the institutions’s basic research in cancer biology, but can also be used for toxicity testing of drugs and therapies, and also for personalised therapy. In the future, structures printed from tumour tissue removed from patients could even be used to test drugs and planned treatments.

The Laboratory of Tumour Biology at the 1st Department of Pathology and Experimental Cancer Research Institute focuses on metabolic changes in tumours and their therapeutic inhibition. To produce bioink for 3D printing, tumour and other cells are isolated from tumour samples received at the institute using enzymes, then mixed with a gel-like matrix material. A special computer-controlled device can print complex tissue-like structures using multiple bioinks at once. Micrometre-precise bioprinting is assisted by compressed air pressure. By cross-linking the matrix material between cells, the printed structure can be stabilised to ensure that the pre-designed shape is maintained (e.g. vascular networks, small tissue discs, different cell layers, etc.). Culture medium is added to the printed structure, and then after a few days, or maybe a few weeks of culture, models of cell-cell interactions similar to real tissues are formed. In general, large numbers of tumour and other cells can be isolated from a small piece of tumour tissue, so many small tissue models of any shape, capable of growing in vitro, can be printed from bioinks containing different cells. These can be used in a wide range of studies, such as testing potential anti-tumour agents or targeted treatments emerging after modern molecular diagnostic procedures. The results can be used not only for basic research projects, but also for planning personalised treatments with more accuracy in the future. Tests that could be developed using the printing process would allow the design of a personalised treatment plan, including drugs selected specifically for the tumour, to be set up at the time of diagnosis. The introduction of this application requires the development of tailored protocols, which are currently being tested on animal tumour tissue samples. Upon a completion of that, testing of the technology in surgical tumours can begin.

Altogether, more than 200 human tumour cell lines are available in the institute’s cell bank. We have started testing the most relevant tumour cells concerning public health – we are printing 3D tissue-like structures from breast and lung tumour cells, and testing the printing process with colon cancer and kidney tumour cells”

– explained Dr. Anna Sebestyén, Senior Research Fellow at the 1st Department of Pathology and Experimental Cancer Research, Head of the Tissue and Cell Culture Laboratory.



The Online Core Facility system at Semmelweis University

The living cell 3D bionic printer structure is now available in the online Core Facility system of Semmelweis University. This includes tools and services that are not only available to university researchers, but also to external researchers for industrial or academic use, upon a service fee or on a collaborative basis.

In this series of articles, we introduce the new research infrastructures to be included in the Core Facility system of Semmelweis University. The Core Facilily website is currently accessible via the internal university network. As soon as these services are available to external partners, this menu item will also be searchable from the public online interface.

In order to operate the 3D bionic printer lab, a professional cell and tissue culture laboratory and animal house are needed as well, the researcher said, adding that the 1st Department of the Institute of Pathology and Experimental Cancer Research has these at their disposal. The unique research infrastructure thus set up is also ready to serve industrial collaborations and external-internal academic cooperation.
Besides tumour research, the 3D bionic printer can be utilized in a wide range of other projects: the pharmaceutical, food and cosmetics industries, for example, may use it to perform toxicity tests on organ or body-on-chip models as an alternative to animal testing. These models involve printing different types of living tissues on small plates using 3D bionic printers, which are supplied and sustained with fluids, nutrients and oxygen by connecting them to different networks that also mimic blood vessels, and performing toxicity tests in the resulting models.
The 3D bionic printer could open up new horizons in research. “In tumour research studies, we typically use animal tests or cellular models called cell lines. The latter are cells isolated from human tumours that can be sustained in vitro and usually adhere to the bottom of culture dishes, to grow in two-dimensional cell cultures. However, the different behaviour of cells in two- and three-dimensional environments, where not only cell growth, but further important characteristics of the cells are altered, is increasingly known. In the living organism, in addition to tumour cells, other cells (e.g. immune cells, blood vessels, connective tissue cells) and other intercellular substances are present within the tumour tissue. The resulting differences in oxygen and nutrient supply are also significant, and somewhat difficult to recreate in two-dimensional cell cultures. This complexity and physiological relations are better modelled in a three-dimensional environment, but animal models are still essential for research. In animal experiments, we induce tumour formation or introduce human tumour cells into the animal body, which is very useful, yet it cannot perfectly demonstrate how tumour cells behave in human tissues, in a tissue microenvironment next to non-tumour human cells,” said Dr. Anna Sebestyén, pointing out the prospective benefits of 3D bionic printing in cancer research.
Treating a tumour is a big challenge. The tumour is constantly changing during interventions, medication and progression. Tissues created with 3D bionic printing, complemented with special microfluidics systems, could be used to model this in the future. Long-lasting 3D tissue-like structures can be used to study how aggressive tumour cell clones are selected out, and how certain tumours become resistant to treatment. Furthermore, the advantages of 3D models can be exploited in drug development as well: new, potential anti-tumour agents can be tested much more efficiently under these conditions than in 2D cell cultures. “Of course, these new types of studies cannot replace executive clinical trials and preventative animal testings, but they can reduce the number of animal experiments and failed phase studies, as they contribute to better select the drugs that are likely to be effective. This could also reduce the high costs of current drug development trials in the future,” she added.
„In addition to the rapid development of molecular biology and diagnostic techniques, in vitro model system developments including 3D bionic printing, which have become available in recent years, could revolutionise cell and tumour biology experiments in the early 21st century. This is going to provide new tools for the development of precision medicine and personalised treatments,” Dr. Anna Sebestyén pointed out.
Ádám Szabó
Translation: Viktória Kiss
Photo: Attila Kovács – Semmelweis University