Interview with Aya Amitai-Lange and Anna Altshuler, women’s force of Brighter at Israel

On the occasion of the 6th International Day of Women and Girls in Science, we interview Aya Amitai-Lange and Anna Altshuler to know a little bit more about them. They are the two women that carry out the Bright project at Technion, Israel.

Both Anna and Aya work at the laboratory of Prof. Ruby Shalom-Feuerstein, at the Technion-Israel Institute of Technology. The research of the lab is focused on the study of fundamental and translational research of skin, cornea and pluripotent stem cells. Inside Brighter project, their role is no less than to provide the cellular models, scientific knowledge about stem cell biology and collaborate on the fabrication and testing of the new engineered tissues using the biomaterial scaffold to be developed by the bio-engineering experts.

Aya and Anna are highly qualified scientists, both holding a PhD, and today, on the International Day of Women and Girls in Science, they share with us some reflections about their personal experiences and the role of women in science. Aya is currently a Research Associate and Lab. Manager and Anna is a Postdoc Researcher, both working on stem cell biology in skin and cornea.

    

When you found out that you wanted to be a scientist?

Aya: After my military service I was searching for the most interesting and suitable profession for me and decided to study Molecular Biochemistry. I found it very exciting to understand the basics of life.

Anna: Already in high school, I was interested in Biology and curious especially stem cells.

Have you encountered any kind of barriers to go in this direction from your family, friends or school?

Aya: Yes. My family encouraged me to pursue an engineering profession, like my father and my big brothers.

Anna: No, my family supported me throughout my entire career.

At some point did you think that being a woman could be a problem in achieving your dream?

Aya: No. I didn’t feel that being a woman is a problem.

Anna: I don’t think so, but the fact is that there are more men as PI than women.

Do you think that your daily/family life has somehow a negative impact on your work due to the fact of being a woman?

Aya: Yes, since I have three young children I find it very challenging to combine my work and my family life. The last year in which my children are at home most of the time due to the pandemic breakout was especially difficult.

Anna: Yes of course, I have a small baby who needs a lot of attention so I can’t work for long hours.

Do you think that initiatives like the International Day of Women and Girls in Science are useful/necessary to make the role of women in science visible?

We both see that in the last few years there is a change in the balance between men and women in senior positions in the Technion. More and more young female scientists get the opportunity to open their own labs and are found to be very successful. Any activity that may support this important change is blessed.

Interview with Elena Martínez, coordinator of Brighter Project

What is your role within Brighter and what it entails?

I am the scientific project coordinator, so I am in charge of supervising the scientific tasks carried out by my team but also of coordinating the different workpackages among the BRIGTHER partners to be sure that deliveries are on time and the project objectives are fulfilled.

Could you tell us a little bit about the concrete work you’re involved in inside Brighter project?

As the main promoters of BRIGTHER new bioprinting concept, IBEC is the in charge of coordinating the full proposal at the scientific and managing level. My role is to propose key experiments that will transform BRIGTHER’s idea from a concept to a first prototype working in a lab environment. Then, I supervise data analysis and interpretation to decide what are the follow-up actions. In practice, at IBEC experiments are carried out by a team composed of two postdocs and one PhD student that I personally supervise.

What is the expected impact of the work you’re doing and of the project as a whole?

The project as a whole is expected to impact in the way the bioprinting process is conceived so far, aiming to improve the main drawbacks of current techniques, which either allow to have high resolution or high printing speed but not both at the same time. BRIGTHER concept will produce a new device based on light-sheet microscopy able to print skin tissue surrogates from custom made polymer materials. High speed printing impacts directly on the cell survival ability, one of the main problems of bioprinting techniques, while high resolution will allow to fine tune the geometry and mechanical properties of heterogeneous tissues such as skin. The work we are performing at IBEC will provide the working parameters of the customized “bioinks” to be successfully used with the BRIGTHER prototype.

In the context of bioprinting of human tissues, what are some of things you’ve found easy/challenging to work with?

Bioprinting human tissues that are functional is a challenging task. Cells have a limited life span when they are outside of their native matrix and are very sensitive to parameters such as shear forces applied. Time is then a crucial point for this task.

Do you have any lessons to share for the future?

I believe the future of bioprinted tissues will come from combining different technological approaches with finely tuned materials that will provide cells with the minimum number of signals sufficient for them to exploit their self-organization capabilities. It will be like mimicking developmental processes but starting with adult cells of the tissues instead of embryonic cells. Probably the use of cell-derived from organoids from adult tissues will be key in this process.


Dr. Elena Martínez obtained her PhD in Physics at the University of Barcelona in 2001 and afterwards she moved to Switzerland to develop a postdoctoral research at the Ecole Polytechnique de Lausanne (EPFL). Back to Barcelona in 2003, her research was funded by one of the prestigious “Ramon y Cajal” Spanish grants at the PCB (Barcelona Science Park) where she was in charge of the technological infrastructure “Nanotechnology Platform”. In 2008 she joined the Nanobioengineering group at IBEC (Institute for Bioengineering of Catalonia) as senior researcher, and from 2013 she leads her own research group at IBEC, the Biomimetic systems for cell engineering lab. Her research group aims to develop biomimetic systems combining engineering microfabrication technologies, tissue engineering and stem cell research. Currently, she is also Associate Professor at the Faculty of Physics from the University of Barcelona.

Brighter project: new light to fabricate biological tissues

© F. Pampaloni, Goethe University Frankfurt, BRIGHTER, 2019

Engineered tissues are key elements for both in vitro and in vivo applications and strongly impact the academy, pharma, and clinical sectors. In the future, laboratory-produced tissues might lead to replace damaged tissues and organs. 3D printing technology is the most used technique to fabricate such tissues, however some challenges must still be solved. The European Project Brighter aims to increase the spatial resolution of the engineered tissues and to speed up the tissue printing process.

Current 3D printers allow researchers and engineers around the globe to print a great variety of objects, with a broad variety of materials, shapes and resolutions. Bioengineering has not lagged this tendency and researchers are now adapting the technique to print human tissues and organs, expanding the limits of a field known as tissue engineering. The success of this approach might represent an enormous advance for the transplantation of organs, reducing the waiting time for patients. Also, it will be a revolution in the drug discovery process and clinical trials, making possible to test new drugs in human organs or tissues instead of using animals or cells in culture. Besides reducing experiments in animals, the use of human tissues is much more adequate and reliable.

The main challenges for the researchers to make this a reality are to produce tissues with the appropriate biological and mechanical properties. Engineered tissues must have a high spatial resolution to recreate the heterogeneous nature of native tissues and must be printed as fast as possible to avoid a decrease in cell viability. The problem is that nowadays none of the 3D bioprinting methods can assure satisfactory levels of both requisites simultaneously.

A new way to print human tissues

The European project Brighter is working on a solution to this problem. Researchers from three leading academic institutions (IBEC in Spain, Goethe University in Germany and Technion in Israel) and two first line industrial partners (Mycronic in Sweden and Cellendes in Germany) form a consortium coordinated by Elena Martínez from the Institute for Bioengineering of Catalonia (IBEC). They are developing a 3D Bioprinting technology able to fabricate tissues at high printing speed and with high spatial resolution by the use of an innovative top-down lithography approach, which is opposite to the bottom-up, layer-by-layer bioprinting methods currently used.

A key aspect of the project is the use of customized hydrogels (materials that provide elastic and hydrated crosslinked network) that mimic the natural extracellular microenvironment of the cells. This extracellular environment, also known as extracellular matrix or ECM, is a key factor in the development of a complex and functional tissue structure and guides cells’ intrinsic self-organizing abilities in the formation of a functional tissue.

Another crucial point is the need to extract relevant information from the 3D cell culture models used in the printing process. To this, Brighter project uses advanced imaging techniques that combine light-sheet illumination and high-resolution digital photomasks to fix the cells into the hydrogels and create 3D structures in a top-down lithography process. The result is the production of complex three-dimensional tissue geometries.

Proof-of-concept: engineering complex skin tissue

The skin is a highly dynamic tissue composed by several layers with particular cell populations and ECM composition. Moreover, vascularized bioengineered skin constructs contain not only the epidermis, but also three essential skin appendages: hair follicles, sebaceous and sweat glands.

Researchers from Brighter combine lithography with cell-laden customized hydrogels to mimic the specific mechanical properties of skin components and its 3D compartments, including wavy niches for stem cell positioning and skin appendix complex architectures. With this technology, researchers expect to print a skin sample of 1 cm2 area and 1 mm thick in about 10 min and with a cell viability of more than 95%, representing a huge improvement of the current printing techniques.

The generation of such a complex tissue structure using the new bioprinting technology from Brighter will represent a real science-to-technology breakthrough towards the realization of on-demand tissue engineering and will strongly impact the academy, pharma and clinical sectors.

Keywords

3D Bioprinting, engineering, tissues, Bioengineering, skin, health, Brighter Project, Europe

Link to the publication on Cordis

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

Current news about science, teaching, and society can be found on GOETHE-UNI online (www.aktuelles.uni-frankfurt.de)

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.