10 November 2022

Spheroid Revolution

Interview with Katherine Vilinsky-Mazur — CEO of a startup developing software for 3D bioprinting of living tissues and organs

Ekaterina Khananova, Habr

Catherine Wilinsky-Mazur, together with the team of the Spheroid Revolution startup, is developing software for 3D bioprinting of living tissues and organs. The solution should make it possible to create meat and fish for food on a bioprinter, as well as, in the future, print live organs for transplantation. The authors state that their technology has no analogues in Russia. The Habra Information Service interviewed Catherine to talk about the startup, technology and prospects of bioprinting.

To begin with, let's imagine a startup a little. Spheroid Revolution is engaged in the complex development of equipment and software for three-dimensional bioprinting. All this is aimed at modeling and simulating the key processes of building bioprinted tissues and organs. The purpose of the development is to increase the efficiency and scale of 3D bioprinting technology. The company is also developing a full-cycle software and hardware package for bioprinting.

14 people are working on the project. Most of the team are researchers or students of the Skolkovo Institute of Science and Technology. Spheroid Revolution employees conduct constant research in the field of physical processes occurring when printing organic tissues with spheroids, the results of which are actively published in leading scientific journals of the world. The company's solutions are primarily intended for use in healthcare and personalized medicine. In addition, some of the key users are research institutes and manufacturers of equipment and software for 3D bioprinting.

"Multicellular spheroid aggregates (spheroids) are a new building material for bioprinting tissues and organs. With the growth of the spheroid, the probability of necrosis of internal cells increases, which prevents their use for printing. We offer an innovative program that evaluates the quality of spheroids, solving the minimax problem (max size, min necrosis) by noninvasive cell control and contributing to the production of spheroids in the required size range. The prototype was tested in the laboratory of 3D Bioprinting Solutions. The purpose of the development is to increase the efficiency and scalability of 3D bioprinting technology," the project card states.

How and when did you decide to develop bioprinting software? What inspired you?

I decided to launch my startup in 2020 while studying at the Innovation courses of Professor Kulish and Nikolaev at Skoltech — I realized that "the very moment" had come. The idea itself originated back in 2018, when I "fell in love" with bioprinting, which was a very new and terribly interesting area for me at that time. The more I learned about this field of science from the scientists I communicated with, from the articles I read, the more it inspired me. The very launch of the project, the very symbiosis, when inspiration comes not only from the idea itself and the knowledge base about the field of science, but also from the realization that next to you are people who, just like you, are burning with a common cause with you and are ready to go in this direction, despite all possible difficulties occurred in 2021. The team is very important for launching the project — so I consider 2021 to be the starting point.

Ideally, what should be the output of the product?

A bioprinting PACK is a hardware and software complex that combines the bioprinter itself, controlled by AI with a computer vision system, with software that simulates the survival of a bioconstruct even before printing, aimed at optimizing the bioprinting process.

Who is on the startup team? Do you cooperate with foreign partners?

The startup team mainly includes graduate students and undergraduates of Skoltech, but also people who are not related to Skolkovo in their main work work with us in the team. In the current political situation, we have refocused on eastern markets and are currently establishing cooperation with foreign companies. MENA is a priority.

How did the work begin?

The work began with a study of the current state of technology. Since we already knew that the problem really exists, we started with a global theoretical study:

1. a literary review on a scientific problem;

2. analysis of the market and competitors;

3. search for similar solutions.

At the same time, we communicated with a large number of potential customers to falsify working hypotheses and clarify product requirements.

Do you use your own research to teach you how to evaluate the quality of biomaterials, or do you take existing ones as a basis?

We do not teach "biomaterial quality assessment", we did not even plan, and we are not going to. It's pointless. We solve partial differential equations. The task is to select optimal conditions for printing and recommend amendments to the experimental process. In the simplest case, we do not use machine learning at all, only solving the diffusion equation with given boundary and initial conditions. In this case, the experimental data are taken from the articles. 

Machine learning within the framework of the project is needed to solve specific narrow tasks, for example, to track printing errors in real time using computer vision methods. To solve these problems, we set up experiments ourselves, since there is no publicly available data on bioprinting artifacts.

Describe the technical aspects in as much detail as possible: what are you writing and testing on.

We write backend and scientific computing in Python, frontend — on React. We use OpenSCAD as a CAD system.

Python stack:

1. Flask as a web server;

2. Celery for task management;

3. numpy/scipy/matplotlib/pandas for data processing and visualization;

4. gmsh for the construction of computational grids;

5. Firedrake for solving equations;

6. OpenCV and Pytorch for computer vision.  

In December last year, a prototype bioprinter was sent to the ISS, printing patches from human cells directly on the body. In your opinion, to what extent is the introduction of such bioprinters into wide circulation realistic in the foreseeable future?

In situ bioprinting is now the closest area of medical bioprinting to production. In the foreseeable future, the introduction into wide circulation is quite realistic, most of the problems with implementation are related to regulations in the field of medical devices.

You mentioned that your technology will allow you to create artificial meat and fish. First of all, in such matters, we are interested in the ratio of price and production costs. Will it be cheaper and more profitable for the manufacturer? Have you already thought about collaborating with manufacturers to test the technology?

3D Bioprinting technology for artificial meat is definitely not new anymore. On this topic, you can read an article about printing an artificial wagyu steak from scientists from Osaka University. The idea of using printing technology to create food naturally follows from an understanding of all the possibilities of bioprinting. On the one hand, it is much easier to produce muscle and fat cells in the laboratory than tissues and organs for implantation. First of all, this is due to the requirements for the product. If cellular structures in medicine require the performance of all basic functions (contraction, excitation, assimilation, growth, reproduction, and so on), then muscle fibers require only a repetition of their structure. In this regard, when we talk about scalable meat production in this way, it is much closer and easier to execute.

Speaking about the price, we must remember that in addition to printing with bio-ink, we must prepare raw materials from cells. You can use muscle cells at once or types of stem cells, but the latter require a lot of preparation. It will take a long time for the cultivation, incubation and differentiation of stem cells. This whole process is labor-intensive and it is very difficult to say that in the future we will be free to buy artificially created meat in a restaurant. With existing technologies, the price will be too high for ordinary people. However, research in bioprinting is being conducted on a larger scale than ten years ago. And one of the key tasks is to reduce the costs of producing this type of artificial food. For us, it is now important to work with the area where the functioning and survival of cellular structures is mandatory. However, we have never turned away from this idea, especially because of its popularity.

Is it possible to print artificial organs and tissues on a bioprinter for human transplantation? It is clear that in theory this option has been discussed for at least 10 years. But is it worth expecting a full-fledged appearance and introduction of this technology into medicine within the same 10-20 years? Will your technology help speed up this process?

Our technology will help speed up this process. However, we cannot influence the process of medical certification, which is quite long, so in any case, 10 years should be laid from the moment of development to the moment of clinical implementation. I think the full-fledged appearance of bioprinting organs for human transplantation is possible everywhere within 20-30 years, no less. However, bioprinting has many other applications, the introduction of which is possible in the coming years: for example, bioprinting of test systems for the development of cosmetology, chemistry, bioprinting for regenerative medicine (in situ bioprinting), and we are focusing on them at the moment. There are also plans to develop the direction of food bioprinting.

How do you assess the past, current and future development of bioprinting in Russia?

The bioprinting market, by existing standards, was born recently, about 15-20 years ago. There are already several large companies in the world in this field, such as Organovo, BioCad. In Russia, there is already a relatively adult and world-famous 3D Bioprinting Solutions. However, apart from us, it is difficult to find other companies in the homeland that are engaged in bioprinting. Basically, everything is at the level of local research in leading laboratories.

If we compare with the world, the number of investments in this area in Russia is not too large because of its unpopularity, in our opinion. Even the global 3D Bioprinting market is about $500 million, which is actually not a very big figure. But the market growth is more than 22%, which is incredibly much even for a BioTech. And here we look at this picture with a positive, since Russia has a good base for research in this area. First of all, this is DeepTech, which already complicates the creation of a product. And it will be difficult in Russia without state support in the field of financing and certification. And there is such support, in our case, in the person of the Skolkovo Foundation, of which we are a resident. As they say, who is looking, he will always find.

If we look into the future of bioprinting in Russia, of course, everything will depend on the interest of large companies and medical centers. If the technology is really in demand here, and there are all reasons for this, taking into account ready-made experiments in bioprinting, then Russia in the bioprinting market will clearly not be at the end and not in the middle of the list.

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