Producing tissue and organs through lithography

Source: Goethe-Universität Frankfurt am Main

EU Project BRIGHTER sets its sights on 3D bioprinting systems with light sheet lithography.

FRANKFURT. The production of artificial organs is a hot research topic. In the near future, artificial organs will compensate for the lack of organ donations and replace animal experiments. Although there are already promising experiments with 3D printers that use a «bio-ink» containing living cells, a functional organ has never been created in this way. A European consortium coordinated by Dr Elena Martinez (IBEC, Barcelona, Spain) and involving the Goethe University Frankfurt is now breaking new ground. The consortium is developing a lithography method that relies on light sheet illumination and on special photosensitive hydrogels that are mixed with living cells.

Bio-printing systems that build up structures layer by layer (bottom-up approach) have considerable disadvantages. On the one hand, the printing process takes far too long, so that the survival chances of the cells in the bio-ink and in the polymerised layers considerably decrease. Furthermore, the extrusion pressure leads to a considerable cell death rate, especially for stem cells. In addition, the resolution of the method, around 300 micrometers, is far too low to reproduce the delicate structures of natural tissue. Finally, it is particularly difficult to integrate complex hollow structures, e.g. blood vessels, into the cell tissue.

«With our project, we want to go the other way round by developing a top-down lithography method,» explains Dr. Francesco Pampaloni from the Buchmann Institute for Molecular Life Sciences (BMLS) at Goethe University. The process works in a similar way to lithography in semiconductor technology. Instead of the semiconductor and the photosensitive layer, which is illuminated by a mask, a hydrogel with photosensitive molecules is used. This is exposed to a thin laser light sheet using the technique invented by Prof. Ernst Stelzer for light sheet microscopy. This leads to the formation of branched chain structures (polymers) that serve as a matrix for colonisation by living cells. The remaining, still liquid hydrogel is washed out.

«This method will enable us to adjust the spatial structure and the stiffness with an unprecedented resolution so that we can create the same heterogeneous microstructures that cells find in natural tissues,» explains Pampaloni. Pampaloni expects that completely new possibilities will emerge for the bio-fabrication of complex tissues and their anatomical microstructures. In addition, the specific properties of the matrix can be used to introduce stem cells into well-defined compartments or to enable the formation of vessels. Further advantages over conventional 3D printing systems are high speed and cost-effective production.

BRIGHTER stands for «Bioprinting by light sheet lithography: engineering complex tissues with high resolution at high speed». Starting in July 2019, the project will be funded for three years as part of the European Union’s renowned and highly selective «Future and Emerging Technologies» (FET) Open Horizon 2020 Programme. BRIGHTER will be financed with a total of € 3,450,000, of which € 700,000 will go to a team led by Dr. Pampaloni in Prof. Stelzer’s Physical Biology Group in the Biosciences Department of the Goethe University. Further partners are the IBEC (Barcelona, Spain, coordination), Technion (Haifa, Israel) and the companies Cellendes (Reutlingen, Germany) and Mycronic (Täby, Sweden).

An image may be downloaded here: http://www.uni-frankfurt.de/78299401
Credit: F. Pampaloni, BRIGHTER, 2019
Caption: Light sheet bio-printing. A hydrogel composed of living cells and photosensitive molecules is deposited in a special cuvette. A thin laser light sheet illuminates the gel following a programmed pattern (green beam). This leads to the formation of 3D micro-structures that reproduce the tissue architecture and function. The remaining, still liquid hydrogel is washed out after the printing process.
Further information: Dr Francesco Pampaloni, Physical Biology, Faculty of Biological Sciences, Riedberg Campus, Phone: (069) 798-42544, fpampalo@bio.uni-frankfurt.de, https://www.physikalischebiologie.de/people/francesco-pampaloni

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Goethe University is a research-oriented university in the European financial centre Frankfurt am Main. The university was founded in 1914 through private funding, primarily from Jewish sponsors, and has since produced pioneering achievements in the areas of social sciences, sociology and economics, medicine, quantum physics, brain research, and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a «foundation university». Today, it is one of the three largest universities in Germany. Together with the Technical University of Darmstadt and the University of Mainz, it is a partner in the inter-state strategic Rhine-Main University Alliance. Internet: www.uni-frankfurt.de

Publisher: The President of Goethe University Editor: Dr. Anne Hardy, Science Editor, PR & Communication Department, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: -49 (0) 69 798-13035, Fax: +49 (0) 69 798-763 12531, hardy@pvw.uni-frankfurt.de.


Wissenschaftliche Ansprechpartner:

Dr Francesco Pampaloni, Physical Biology, Faculty of Biological Sciences, Riedberg Campus, Phone: (069) 798-42544, fpampalo@bio.uni-frankfurt.de, https://www.physikalischebiologie.de/people/francesco-pampaloni

 

New EU project at BMLS

Source: Cluster of Excellence Frankfurt Macromolecular Complexes

The new project “Bioprinting by light sheet lithography: engineering complex tissues with high resolution at high speed” (BRIGHTER) will be funded by the prestigious and highly selective Future and Emerging Technologies EU programme (FET Open, part of Horizon 2020). The EU will support this three year project with a grant of 3,450,000 €  of which 700,000 € will go to the Physical Biology Group of the Faculty of Biological Sciences at Goethe University. The consortium of BRIGHTER includes Goethe University Frankfurt, Germany), IBEC (Barcelona, Spain, consortium coordinators), Technion (Haifa, Israel) as well as the companies Cellendes (Reutlingen, Germany) and Mycronic (Täby, Sweden).

The Frankfurt team, led by BMLS researcher Francesco Pampaloni, plans to realize a bioprinting system based on an innovative light sheet lithography system. “I am very excited by the opportunity to create a breakthrough bioprinting technology within the BRIGHTER project. With outstanding international partners, we have a unique opportunity to build a truly innovative system that prints artificial skin constructs at high speed. BMLS offers a unique interdisciplinary environment and the appropriate infrastructure to carry out this demanding endeavour. I am certain that a lot of synergy with the other BMLS groups will be fostered by BRIGHTER”, says Francesco Pampaloni.

The project will be carried out in Ernst Stelzer’s group in the BMLS and will start in July.

Barcelona hosts the kick-off meeting of the EU project BRIGHTER

The partners have taken the opportunity to explain not only the role and responsibilities of everyone but also the main production and research lines of the project

The Kick-Off meeting of the EU project BRIGHTER (Bioprinting by light sheet lithography: engineering complex tissues with high resolution at high speed), an initiative led by Dr Elena Martinez from the Institute for Bioengineering of Catalonia in Barcelona (IBEC), took place this week in Barcelona.

The event has brought together all the partners of the project, who have taken the opportunity to introduce themselves and explain their roles and responsibilities. The consortium members also presented the main production and research lines of the project and defined the work plan for the following months.

Among the beneficiaries of BRIGHTER we can find the Institute for Bioengineering of Catalonia (IBEC), that covers most bioengineering fields, from basic research to medical applications; the Buchmann Institute for Molecular Life Sciences (BMLS) of the Goethe University Frankfurt (GUF), which is focused on understanding the molecular mechanisms underlying cellular functions; the Technion–Israel Institute of Technology, which is the Israel’s primary technological university; and the companies Mycronic and Cellendes, from Sweden and Germany, respectively.

Main Production and Research Lines

All the partners of BRIGHTER will work together until 2022 to make our lives easier. The researchers involved in this pioneering project aim to importantly assist, for example, those on the waiting list for a donor organ by developing the first 3D bioprinting system able to produce functional organs.

It is true that, in recent years, the number of donors has increased substantially, but lots keep dying every year while they wait for a kidney transplant or other kind of transplant. Given this scenario, find other ways to give someone a ‘second chance on life’ is fundamental, and BRIGHTER may have the key to all of this. Concretely, in the next three years the scientists will be focused on produce artificial organs by using 3D printers containing living cells with the purpose of compensate for the lack of organ donations and replace animal experiments.

For this, they will develop a top-down lithography method that will enable the researchers adjust the spatial structure and the stiffness with an unprecedented resolution to create the same heterogeneous microstructures that cells find in natural tissues.