Printing of an Organ within 30 Minutes and Other Perspectives of 3D Bio Printing

There is a tendency to ecological compatibility in medicine today: the doctors are looking for ways to renounce the use of artificial materials.  The technology of 3D bio printing is becoming more urgent and is used for printing of living tissues and organs in the shortest possible time - 30 minutes. An American professor of the University in Virginia, Vladimir Mironov, in his recent interview for Think Blue told what to expect from transplantology in the future.

- How did the technology of 3D bio printing appear? Who came up with the idea of using three-dimensional printing in medicine?

- Those who preceded its emergence, there were many people but I will focus on the man who discovered the principle of cell fusion. His name is Bohr. The scientist was working on the experiment with tadpoles when his wife called him to have dinner. Bohr went to eat and forgot about his experiment, leaving the tadpoles on the desktop. When he returned to the experiment in the morning, the scientist saw that they were fused.

- What is the connection of the cell fusion with bio printing?

- It is the basis of 3D bio printing. The process of printing, more correctly the tissue-engineering structure, is only a half of the story. It is necessary that located in special capsules cells to be fused. This differs bio printing from printing of plastic. When using artificial materials it is only necessary to melt them, define the shape, and the object is ready. In case of bio printing the process is more complicated. I always compare it with the great invention of Gutenberg. To print a book, we need a text, paper, ink, and a letter press. To print an organ, we need the same number of things: bio ink, cartridge, tissue spheroids, bio paper or hydrogel, which houses the cells, and a bio printer.

- Tell us all about it. Let's start with the components, namely, tissue spheroids.

- Tissue spheroids are liquid, the basic material for 3D bio printing, which can keep a certain shape. The term "spheroids" comes from the word "sphere" that describes the shape of this "brick" for the 3D printing as three dimensional. Spheroid is a hydrogel composed of 99% of water (like a jelly). They contain living cells, and what is the most important fact, they tend to fuse. It is the same process as that of Bohr and his two tadpoles. It is important that the spheroids fuse in both the horizontal and vertical directions. This enables to form three-dimensional structures

 

- How are living cells transferred in the hydrogel and where do you get them from?

- Let's begin with cells. When living in the United States, you can witness an interesting effect. Either due to fatty food or food additives, but people here get fatter very quickly. And this happens even with people of other nationalities. Americans have a special device, which is able to extract stem cells out of fat, which then survive and do not cause immune rejection. We have received an exclusive license to use this device in Russia, so soon there will be printed organs of Russian production. The main thing is the presence of stem cells.

- What can you say about the mysterious spheroids?  Will they be created manually?

- No, this process involves a robot, which adds cell suspension to the hydrogel. The next step is forming droplets - spheroids which are then sent to the 3D printer. As the result we use water which composes 99% of a hydrogel. This technology allows you to create 6 thousand spheroids. The next step will be a microfluidics technology, which allows you to create 10 thousand drops per second.

- How long does the printing process of one organ last?

- On average, this process takes 30 minutes. But to be precise we obtain not an organ but a tissue-engineering structure which is then placed in a bioreactor, and only after some time, you can obtain an organ. It has a high degree of endurance, so even the need for stitching disappears.

- Please describe the process of kidneys printing?

- It does not matter what organ to print, since all organs are printed under one technology. To begin with, a thin layer of hydrogel is used, and then spheroids fuse in the horizontal and vertical directions. At the moment, with the help of a special program three-dimensional image of organ is modelled and there is a virtual dissection of this model into layers. Each of them is represented in detail together with the holes for the vessels and other nuances on the screen. Next stage, after modelling, is directly the layers printing. One of the most important tasks is to print the vascular tree. Printing without vascular tree can be compared to a group of people being closed for a week in an office without meal. Naturally, there will be the destruction, and subsequently they will die. A similar situation happens with a printed organ: without oxygen and nutrients the tissue dies.

 

- The process of 3D object creation is not an easy task. And the cost of devices for 3D printing is probably very high ... Will this technology be commercially successful?

- As soon as the first personal computer appeared, it was said that they could sell only three PCs. This is because at that time the machine did not have many tasks. It was difficult to imagine that everyone would have its own computer and perform a lot of tasks with its help. The same situation can be observed with a three-dimensional printer. Today we are witnessing a revolution. The cost of a conventional printer is $ 70, and it works in two directions, namely moving from the right to the left. Adding a third coordinate axis, respectively, increases its cost by additional $ 50. Today, as far as I know, the cost of the cheapest 3D printer is $ 347. However, it concerns only ordinary 3D printers, and a 3D bio printer is not the case.

- What is the difference?

- There is no market for them. There are commercial 3D bio printers at exorbitant prices. The cost of the Swiss printer, for example, is 500 thousand dollars; the German printer is in the same price category. The American version is cheaper, about 200-250 thousand dollars, but it is characterized by a primitive design. It's the same thing as to compare the "Mercedes" with a pen. Everything happens due to the absence of a market. If it is necessary to run the company, the price automatically increases. So the commercial 3D bio printers are an economic reality. However, how much printers can be sold, and who is going to buy them is another question.

- But still, is there a confidence that 3D bio printers will be commercially successful?

- I hope so. This can save a lot of lives. While standing in line for an organ 18 people die every day. Also, the printer will provide a significant cost savings when compared, for example, with dialysis, which in the United States costs about 1 million dollars if we calculate for the period of 12 years (one year costs 75 thousand dollars). If the kidney is printed on a 3D printer, then its price, including a surgery, will not exceed 500 thousand dollars. In case of market, this cost can be reduced, but even if we count to the max, 3D bio printing saves half a million dollars for each patient.

- Do you evaluate 3D printing as the only correct way of transplantation? Are there any other options?

- Of course, other options may also exist. However, it is a big question whether they are eco-friendly and safe. Of course, we can go back to the XIX century and continue to address prostheses - artificial organs. As I know, even today they make artificial hearts. But, on the other hand, just think about it: a person with an artificial hand, heart and kidney. People will turn into someone like Tin Woodman, being half alive. Foreign artificial materials should not be present in the living body. There is another, very questionable method:  - it is purified from the cell organs, in other words, used organs. They are called "decellularised". The corpse or a pig’s organ is removed and sent to a special machine with a "powder". An organ is called detergent because only its frame is left, but living cells are absent. This process is similar to three-dimensional printing, but with a different composition. Organ transplantation occurs and everybody is happy ... In the beginning there were doubts concerning the fact where we can find such number of organs, if they are needed for transplant. In fact, a large number of organs are not suitable and they are sent to the trash, and so to find a donor is not a problem.

- Why, in your opinion, is this method "wrong"?

- There is another serious "but", which is not taken into account by many people. The problem is that today, the highest level of endothelialization is 70%. What is endothelialization? The organ purified from cells has channels, which act as vessels. To make blood move to one of them, the vessels must be covered with endothelium (the thin tissue), which is located between the vessel and the blood itself. If it is absent, a thrombus will be created at this place. If the vessel is small, the blood flow is interrupted. If the vessel is large, thrombus grows and can come off. All this may lead to disability and death. Therefore, until the problem of endothelialization is solved, this method is potentially dangerous. In the United States, for example, if one patient dies, such direction in transplantation will be closed forever.

- Is it necessary to solve the problem of endothelialization when printing an organ? In both cases the scheme is the same - in the end we obtain the same scaffold (frame of an organ)?

- No. 3D bio printer can print not only an organ that has the blood vessels but also endothelial tissue, so there should be no problem.

- How can a surgery correspond to modern lifestyle?

- According to my good friend, the development of surgery of the XXI century should be based on three main things. To begin with, it should not be invasive. It means that it is not necessary during the surgery to break the integrity of tissues. In the movie, when we are watching the scene of a surgery, we can hear the words: "Scalpel please!". It is high time this expression to go into oblivion. The second point: a surgery should be at an extremely low price. But the third point is the most important: the basis of surgery should be biology. Or, at least, all of the innovative developments and methods of treatment must be inspired by it. It means that scientists and doctors should abandon the use of artificial materials, strive to be closer to nature.

- In your opinion, does the method of 3D printing comply with a criterion of ecological compatibility?

- 3D printing has many differences from all the techniques that I called formerly, and they are as follows: firstly, the three-dimensional printing is a robotic technology, and human intervention is necessary only to ensure that a computer can get a task. Secondly, there is no need to "wash" dead organs and make something of artificial materials. It uses a layering fabrication and the layers are the thinnest. Due to this, a scaffold (a frame of an organ) becomes mobile and survives easily. Thirdly (which is here the most important), we use only the live cells, namely tissue spheroids.

- Please make a prediction: when will the first organ be printed on a 3D bio printer for its further transplantation?

- I suppose that the first organ will be printed in 2030. In the near future we are planning to create our own bio printer, which will be more perfect and affordable, in comparison with all the models that are currently on the market. Next step is to print tissues, and then organs.

- If you can print the frame of an organ, or a scaffold, is it possible to printing a living organism?

- In the future, everything will be possible. At the moment scientists have already printed the retina, as well as neural networks and connections. Everything is quite simple. The robot consists of three parts: a sensor (for perception of the world), a transducer (for signal transmission) and an actuator (for implementation of any action). In Greece, for example, they announced a European grant for creation of soft bio-robots. I saw a moving elephant trunk, and the tentacles of an octopus. There is also a floating jellyfish, which is difficult to distinguish from live. Many things that used to be fantastic ideas have now become a reality.  Many people, including scientists, often said: it is science fiction. Today there is no such thing as science fiction in the science; it is replaced by scientific eventness. And therefore, there is no doubt that all that was fiction, sooner or later, will be implemented. Read Jules Verne.