3D printing bioprinting

3D Bioprinting of Living Tissues

Progress in drug testing and regenerative medicine could greatly benefit from laboratory-engineered human tissues built of a variety of cell types with precise 3D architecture. But production of greater than millimeter sized human tissues has been limited by a lack of methods for building tissues with embedded life-sustaining vascular networks.

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In this video, the Wyss Institute and Harvard SEAS team uses a customizable 3D bioprinting method to build a thick vascularized tissue structure comprising human stem cells, collective matrix, and blood vessel endothelial cells. Their work sets the stage for advancement of tissue replacement and tissue engineering techniques. Credit: Lewis Lab, Wyss Institute at Harvard University

Multidisciplinary research at the Wyss Institute has led to the development of a multi-material 3D bioprinting method that generates vascularized tissues composed of living human cells that are nearly ten-fold thicker than previously engineered tissues and that can sustain their architecture and function for upwards of six weeks. The method uses a customizable, printed silicone mold to house and plumb the printed tissue on a chip. Inside this mold, a grid of larger vascular channels containing living endothelial cells in silicone ink is printed, into which a self-supporting ink containing living mesenchymal stem cells (MSCs) is layered in a separate print job. After printing, a liquid composed of fibroblasts and extracellular matrix is used to fill open regions within the construct, adding a connective tissue component that cross-links and further stabilizes the entire structure.

Confocal microscopy image showing a cross-section of a 3D-printed, 1-centimeter-thick vascularized tissue construct showing stem cell differentiation towards development of bone cells, following one month of active perfusion of fluids, nutrients, and cell growth factors.

The structure was fabricated using a novel 3D bioprinting strategy invented by Jennifer Lewis and her team at the Wyss Institute and Harvard SEAS. Credit: Lewis Lab, Wyss Institute at Harvard University

The resulting soft tissue structure can be immediately perfused with nutrients as well as growth and differentiation factors via a single inlet and outlet on opposite ends of the chip that connect to the vascular channel to ensure survival and maturation of the cells. In a proof-of-principle study, one centimeter thick bioprinted tissue constructs containing human bone marrow MSCs surrounded by connective tissue and supported by an artificial endothelium-lined vasculature, allowed the circulation of bone growth factors and, subsequently, the induction of bone development.

This innovative bioprinting approach can be modified to create various vascularized 3D tissues for regenerative medicine and drug testing endeavors. The Wyss team is also investigating the use of 3D bioprinting to fabricate new versions of the Institute’s organs on chips devices, which makes their manufacturing process more automated and enables development of increasingly complex microphysiological devices. This effort has resulted in the first entirely 3D-printed organ on a chip – a heart on a chip – with integrated soft strain sensors.

1/7 Cross section of long-term perfusion of HUVEC-lined (red) vascular network supporting HNDFladen (green) matrix.
2/7 Top-down view of long-term perfusion of HUVEC-lined (red) vascular network supporting HNDFladen (green) matrix.
3/7 Photograph cross section of printed tissue construct housed within a perfusion chamber.
4/7 Photograph cross section of printed tissue construct housed within a perfusion chamber.
5/7 Photograph of a printed tissue construct housed within a perfusion chamber.
6/7 Photograph of vasculature network and cell inks.
7/7 Photograph of 3D printed vasculature network (red) within Red is the

Bioprinting, explained simply! - CELLINK

Bioprinting is an additive manufacturing process similar to 3D printing – it uses a digital file as a blueprint to print an object layer by layer. But unlike 3D printing, bioprinters print with cells and biomaterials, creating organ-like structures that let living cells multiply. Although bioprinting is a relatively new technology, it has huge potential to benefit industries like regenerative and personalized medicine, drug discovery and cosmetics. Find out how bioprinting works.

The three basic steps of bioprinting:

1. Pre-bioprinting. This involves creating a digital file for the printer to read. Today, these files are often based on CT and MRI scans. Researchers prepare cells and mix them with their bioink, using a live-cell imaging system to ensure there are enough cells to bioprint a tissue model successfully.

2. Bioprinting. Researchers load the cell-laden bioink into a cartridge and choose one or multiple printheads, depending on the structure they’re trying to build. Developing different types of tissue requires researchers to use different types of cells, bioinks and equipment.

3. Post-bioprinting. Most structures are crosslinked to become fully stable. Crosslinking is usually done by treating the construct with either ionic solution or UV light – the construct’s composition helps researchers determine what kind of crosslinking to use. Then the cell-filled constructs are placed inside an incubator for cultivation.

What are (some of) the applications?

Today’s bioprinting technologies are still new to many researchers. As scientists in the field continue making discoveries, bioprinting can have a huge impact on a range of application areas.

Drug development:
Many of today’s studies rely on living subjects – an inconvenient and expensive method for both academic and commercial organizations. Bioprinted tissues can be used instead during the early stages, providing a more ethical and cost-effective solution. Using bioprintined tissue can help researchers determine a drug candidate’s efficacy sooner, enabling them to save money and time.

Artificial organs:
The organ donation list is so long that patients wait years before getting the help they need. Being able to bioprint organs could help clinicians keep up with patients or eliminate the list entirely. While this solution is far down the line, it is one of the most impactful possibilities in the field.

Wound healing:
A lot of tissue-specific bioinks are available today, enabling researchers to work with artificial skin cells, neurons, hepatocytes and more. One day, clinicians could use these models for therapeutic procedures like skin grafts, bone bandages for combat wounds or even plastic surgery.

This is still a new and emerging field – biocompatible 3D printing was invented in the early 1980s, with cell-embedded bioprinting being invented in 2003 by Thomas Boland, and we’ve come a long way in a short time! As more researchers get access to the latest bioprinting technology, the innovating will only accelerate. One thing is for sure: we can’t wait to see what CELLINK’s collaborators are discovering in just a few years’ time!

Organ printing: how 3D bioprinting technology has advanced and what is hindering its development In research centers and hospitals around the world, advances in 3D printing and bioprinting are providing new opportunities for human treatment and scientific research.

In the coming decades, bioprinting could be the next major milestone in healthcare and personalized medicine.

Let's talk about bioprinting technology, the latest advances in the industry and the limitations that professionals face.

How a 3D printer works

Traditional printers, like the one you have at home or office, work in two dimensions. They can print text or images on a flat surface (usually paper) using the x (horizontal) and y (vertical) dimensions. 3D printers add another dimension - depth (z). During the printing process, the printer heads can move up and down, left and right, back and forth, but instead of delivering ink to paper, they distribute various materials - polymers, metal, ceramics and even chocolate - until the "print" of a holistic, voluminous object , layer by layer in a process known as "additive manufacturing".

To create a 3D object, you need a blueprint for it, a digital file created with modeling software. After its creation, the computer-generated model is sent to the printer. Your chosen material is loaded into the machine and ready to be heated to easily flow out of the printer nozzle. As the printer reads the plan, its head moves, depositing successive layers of the selected material to create the final product.

As each layer is printed, it is solidified either by cooling or by mixing two different solutions delivered by the printer head. The new layers precisely lay down on the previous ones to make a stable, cohesive element. In this way, you can create almost any shape, including a moving one.

3D printing allows you to create objects with geometric structures that would be difficult or impossible to make in other ways. A wide range of products are already being created using 3D printers, including jewelry, clothing, toys, and high-end industrial products. Even a 10-year-old Moscow schoolboy has learned how to work with a 3D printer: he prints 3D figures to order and sells them through Instagram.

How a bioprinter works

Bioprinters work in much the same way as 3D printers, with one key difference - they deposit layers of biomaterial, which can include living cells, to create complex structures such as blood vessels or skin tissue.

Living cells? Where do they get them? Every tissue in the body is made up of different types of cells. The required cells (kidney, skin, and so on) are taken from the patient and then cultured until there are enough of them to create "bio-ink" that is loaded into the printer. This is not always possible, therefore, for some tissues, stem cells are taken that are capable of becoming any cell in the body (organism), or, for example, porcine collagen protein, seaweed and others.

Often used in bioprinting is chitosan, a polysaccharide obtained from the external skeleton of mollusks (eg shrimp) or by fermenting fungi. This material has high biocompatibility and antibacterial properties. Its disadvantage is the low rate of gelation. Another popular material is a polysaccharide isolated from seaweed called agarose. Its advantages are high stability and the possibility of non-toxic cross-linking during research. However, this biomaterial does not decompose and has poor cell adhesion (the ability of cells to stick together with each other and with other substrates).

Collagen, a primary structural protein found in the skin and other connective tissues, has a high biological significance. It is the most abundant protein in mammals and a major component of connective tissue. Its disadvantages for bioprinting include the property of acid solubility. More information about biomaterials can be found here.

Based on computer designs and models, often scans and MRIs taken directly from the patient, the printer heads place the cells exactly where they are needed and within a few hours an organic object is built from a large number of very thin layers.

Organovo bioprinter creates tissues that mimic the structure and composition of various human organs

Source: Pbs. org

Scaffolding for ear or nose replacement at Wake Forest University in Winston-Salem, North Carolina

Source: CBS News

Computer displays an image of a "scaffold" for the human ear, created in the laboratory of Wake Forest University in Winston-Salem, North Carolina

Source: CBS News

Usually more than just cells are needed, so most bioprinters also supply some kind of organic or synthetic "glue" - a soluble gel or collagen scaffold to which cells can attach and grow. This helps them form and stabilize in the correct shape. Surprisingly, some cells can take the correct position on their own without any "scaffolding". How do they know where to go? How do embryonic cells develop in the uterus, or does adult tissue move to repair damage? Same here.

Universities, researchers and private companies around the world are involved in the development of bioprinting technologies. Let's take a look at some of the amazing things they are working on.

Bioprinting in Russia

3D Bioprinting Solutions is a biotechnology research laboratory founded by medical company INVITRO. The activity of the laboratory is the development and production of bioprinters and materials in the field of three-dimensional bioprinting and scientific research. August 23, 20193D Bioprinting Solutions laboratory sent a new batch of cuvettes to the ISS to continue experiments on bioprinting in space, which began in 2018. This was reported in the press center of the laboratory. This time it is planned to use organic and inorganic components to assemble bone tissue on the world's first space bioprinter Organ.Aut.

Symposium "Biofabrication in Space"

Source: Zdrav.Expert

Organ.Aut magnetic bioprinter

Source: Zdrav.Expert

The astronauts will also grow protein crystals and experiment with printing biofilms of bacteria to study their behavior in zero gravity. Russian scientists expect to receive unique scientific data that can be applied in the development of new drugs.

Scientific director of 3D Bioprinting Solutions and leading researcher of the Institute of Regenerative Medicine, Candidate of Medical Sciences Vladimir Mironov, in his speech at the Department of Anatomy of Sechenov University on September 2, noted: “Living cells, tissues and human organs will be synthesized already in the current century. To do this, morphological sciences, such as microscopic anatomy and histology, must be digitized or digitalized, that is, digitized and made available for computer programs of robotic bioprinters, since without digital models it is impossible to print human tissues and organs.”

Bioprinting around the world

Every year, millions of people around the world need bone grafting. Modern bone grafts often use cement-based synthetic material in combination with the patient's own bone. However, the use of these materials has a number of limitations - some transplants caused rejection and inflammatory processes in patients. Reproduction of the natural bone-cartilage "interface" has also been problematic.

However, a team at Swansea University in 2014 developed a bioprinting technology that allows the creation of an artificial bone prosthesis in the exact shape of the desired bone, using a biocompatible material that is both durable and regenerative. At the same time, scientists from the University of Nottingham in England were working on similar studies.

It takes about two hours to print a small bone. Therefore, surgeons can do it right in the operating room. This part of the bone is then covered with adult stem cells that can develop into almost any other type of cell. This is combined with bio-ink from the printer, a combination of polylactic acid (which provides mechanical strength to bone) and alginate, a gel-like substance that serves as a shock-absorbing material for cells. The end product is then implanted into the body, where it will completely disappear within about three months and be replaced by new bone.

Researchers hope that in the future, bioprinted bones can be created with sufficient reliability to support complex spinal reconstruction, and that the bone material will be further improved to increase its compatibility with cartilage cells.

Source: ETH Zurich

Successful 3D printing of human cartilage may soon completely replace artificial implants for people in need of reconstructive surgery. Back in 2015, scientists in Zurich developed technology that would allow hospitals to print a full-size human nose implant in less than 20 minutes. They believe that any cartilage implant can be made using their technique.

Researcher Matti Kesti described the technology as follows:

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“A serious car accident can cause the driver or passenger to suffer complex nose injuries. The nose can be restored by creating a 3D model on a computer. At the same time, a biopsy of the patient is performed and cartilage cells are removed from the victim's body, such as from a knee, a finger, an ear, or fragments of a broken nose. The cells are spawned in the laboratory and mixed with the biopolymer. From this suspension, a model of nasal cartilage is created using a bioprinter, which is implanted into the patient during surgery. In the process, the biopolymer is used simply as a mold. It is subsequently broken down by the body's own cartilage cells. And in a couple of months it will be impossible to distinguish between the graft and the person’s own nasal cartilage.”

Matti Kesti

Since the implant was grown from the body's own cells, the risk of rejection will be much lower than for an implant made of, say, silicone. An additional advantage is that the bioimplant grows with the patient, which is especially important for children and young adults.

If a person is severely burned, healthy skin can be taken from another part of the body and used to cover the affected area. Sometimes intact skin is missing.

Researchers at Wake Forest School of Medicine have successfully designed, built and tested a printer that can print skin cells directly onto a burn wound. The scanner very accurately determines the size and depth of damage. This information is sent to a printer and skin is printed to cover the wound. Unlike traditional skin grafts, it only takes a patch of skin one-tenth the size of a burn to grow enough cells to print. While this technology is still in the experimental stage, the researchers hope that it will be widely available within the next five years.

As already mentioned, 3D printers print products in layers, and since the skin is a multi-layered organ with different types of cells, it is well suited for this type of technology. However, researchers still have a lot of problems to solve, in particular, how to prevent damage to cells from the heat generated by the printer. And of course, like most parts of the human body, the skin is more complex than it first appears—there are nerve endings, blood vessels, and a host of other aspects to consider.

Blood vessels

Biomechanical engineer Monica Moya holding a petri dish with printed alginate-based biotubes. Biotubes can act as temporary blood vessels similar to blood vessels that help create a patch of living tissue.

Source: embodi3D

With tens of thousands of miles of veins, arteries and capillaries in the human body, researchers are working to replace them if they ever wear out. The creation of viable blood vessels is also essential for the proper functioning of all other potential bioprinted body parts.

Biomechanical Engineer Monica Moya of Livermore National Laboratory. Lawrence uses bioprinting to create blood vessels. The materials created by her bioprinters are engineered to allow small blood vessels to develop on their own.

This development takes time, so vials of cells and other biomaterials are printed to help deliver vital nutrients to the printed environment. After a while, self-assembled capillaries connect with bioprinted tubes and begin to deliver nutrients to cells on their own, mimicking the work of these structures in the human body.

Internal organs

Many researchers hope that in 20 years the lists of patients waiting for organ transplants will become a thing of the past. They envision a world where any organ can be printed and transplanted in just a few hours, without rejection or complications, because these organs will be created from body cells according to the individual characteristics of each patient. Currently, bioprinting of fully functional complex internal organs is not possible, but research is ongoing (and not without success).

Bladder

For example, the bladder is already printed. In 2013, at Wake Forest University in the US, researchers successfully took cells from a patient's original, poorly functioning bladder, cultured them, and added additional nutrients. The 3D shape of the patient's bladder was then printed and the cultured cells soaked through it. The form was placed in an incubator and, when it reached the desired condition, it was transplanted into the patient's body. The mold will eventually collapse, leaving only the organic material. The same team successfully created viable urethras.

Physicians and scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) were the first in the world to create laboratory-grown organs and tissues that were successfully transplanted into humans. Right now they are working on growing tissues and organs for more than 30 different areas of the body, from the kidneys and trachea to cartilage and lungs. They also aim to accelerate the availability of these treatments to patients.

Scientists in Australia are doing similar research as well. They used human stem cells to grow a kidney organ that contains all the necessary cell types for a kidney. Such cells can serve as a valuable initial source for bioprinting more complex kidney structures.

MD, Professor of Urology, Professor of the Institute of Regenerative Medicine Anthony Atala shows a kidney created by a bioprinter. A modified desktop inkjet printer sprays cells instead of ink. The cells were cultured from the patient and the structural template for the kidney was obtained from the MRI (so it is the correct size and shape).

Using this technology, back in 2001, Atala printed and successfully transplanted a bladder into a young man, Jake.

Source: TedEd

Heart

Heart cells, laboratory-grown organelles. Source

Surprisingly, it is the human heart that can become one of the easiest organs to print, since, in fact, it is a pump with tubes. Of course, everything is not so simple, but many researchers believe that humanity will learn to print hearts before kidneys or liver.

Researchers at the Wake Forest Institute for Regenerative Medicine in April 2015 created "organoids" - 3D printed fully functional, beating heart cells.

In April 2019, Israeli scientists printed the world's first 3D heart. It is still very small, the size of a cherry, but it is able to perform its functions. The 3D heart with blood vessels uses personalized "ink" of collagen, a protein that supports cell structures, and other biological molecules.

A Tel Aviv University researcher holds the world's first 3D printed heart on April 15, 2019.
Source: Haaretz

“This is the first time anyone anywhere has successfully designed and printed a whole heart with cells, blood vessels, ventricles and chambers,” said Tel Aviv University scientist Professor Tal Dvir.

So far, scientists have been able to print tissue from cartilage and the aortic valve, for example, but the challenge has been to create tissue with vascularity—the blood vessels, including capillaries, without which organs cannot survive, let alone function.

The Tel Aviv scientists started with human adipose tissue and separated the cellular and non-cellular components. They then reprogrammed the cells to become undifferentiated stem cells, which could then become cardiac or endothelial. Endothelium - a single layer of flat cells lining the inner surface of the heart cavities, blood and lymphatic vessels. Endothelial cells perform many functions of the vascular system, such as controlling blood pressure, regulating the components of blood clotting, and the formation of new blood vessels.

Non-cellular materials, including a large amount of proteins, were processed into a "personalized hydrogel" that served as "printing ink".

It will be years before this technology can create organs for efficient transplantation. However, the achievements of scientists in Tel Aviv are a huge milestone along the way.

Medical research and pharmacology

One of the key potential uses for bioprinted living materials is in the field of medical and drug research. Bioprinted tissues have several cell types with different densities and key architectural features. This allows researchers to study the impact of various diseases on the body, the stages of disease progression and possible treatments in the natural microenvironment.

One of the most impressive developments in recent years is the development of a desktop brain at the ARC Center of Excellence in 2016. The researchers were able to use a 3D printer to create a 3D printed six-layer structure that includes nerve cells that mimic the structure of brain tissue.

This opens up huge potential benefits for researchers, pharmaceuticals and private companies, because it will allow them to test new products and drugs on tissue that accurately reflects the responses of human brain tissue, as opposed to animal samples, which may cause a completely different response. The desktop brain can also be used to further investigate diseases such as schizophrenia or Alzheimer's.

We are far from printing the brain, but the ability to arrange cells to form neural networks is a significant step forward. By allowing researchers to work with human tissue in real time, testing processes can be greatly accelerated and results can be more realistic and accurate. It will also reduce the need to use laboratory animals for medical tests and potentially dangerous human testing.

Medical simulators and data registries

Source: Simbionix

About 3,000 medical simulators are currently in use around the world to help doctors practice complex procedures. Virtual blood vessels, 3D printed organs... and no animal suffers!

The American company 3D Systems created an industry segment called VSP (Virtual Surgical Planning). This approach to personalized surgery combines expertise in medical imaging, surgical simulation and 3D printing. Surgeons using the Simbionix medical simulator for the first time often report feeling physical pain while empathizing with their virtual patient - the experience is so realistic. Organs and tissues look completely real. When stitching an organ, the surgeon sees on the screen a needle that enters the tissue, and pulls the thread. If the doctor does something wrong, the virtual blood vessels break and the organ begins to bleed. These simulators were developed by the Israeli company Symbionix, which was acquired by 3D Systems in 2014.

On September 3, 2019, the Radiology Society of North America (RSNA) and the American College of Radiology (ACR) announced the launch of a new 3D Medical Printing Clinical Data Registry to collect data on treatment outcomes using 3D printing at the point of care. This information will be a powerful tool to assess and improve patient care in real time, drive ongoing research and development, and inform patients and healthcare professionals about the best course of care.

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“The creation of a joint RSNA-ACR 3D printing registry is essential to the advancement of clinical 3D printing. The registry will collect data to support the appropriate use of this technology and its implications for clinical decision making.”

William Widock, Professor of Radiology at the University of Michigan and Chairman of the RSNA 3D Printing Special Interest Group (SIG)

According to RSNA, the information in the registry will allow for the necessary analysis to demonstrate the clinical value of 3D printing. Due to the wide variety of clinical indications, different technologies for creating physical models from medical images, and the complexity of the models, it is problematic to choose the optimal treatment method. The registry will help solve this problem.

Bioprinting software

Bioprinter and bioprinting software manufacturer Allevi introduced Allevi Bioprint Pro software on September 5, 2019. Built-in model generation and integrated slicing will allow you to focus more on experimenting, rather than setting up the printer. The program runs entirely in the cloud, which means you can create your biostructures, define materials, and track prints right from a web browser on any computer.

According to the development team, the new bioprinter with the above software is powerful and easy to use and represents another piece of the puzzle on the way to 3D printed organs.

At the same time, CELLINK, the first bio-ink company, announced the launch of a new product to become the most flexible bio-printing platform on the market. The BIO X6 bioprinter, which has no analogues at the moment, has the ability to combine more bioprinting materials, cells and tools.

Why is this taking so long?

Complex body structure

The human body and its various components are much more complex than a plastic toy. The human organ has a complex network of cells, tissues, nerves, and structures that must be arranged in specific ways to function properly. From placing thousands of tiny capillaries in the liver to actually getting a printed heart that "beats" and contracts in the human body, there is still a lot of research and testing.

Legal regulation

In addition, bioprinting technologies, like all new medical treatments, must pass safety tests and due process of regulation before they become available.

Special software and hardware

It also takes time to develop special software and hardware. These programs can be written only with the appropriate data (medical, clinical, statistical, mathematical, and so on), which someone must first collect, analyze, systematize and digitize.

Working through all of these steps requires the integration of technologies from various fields, including engineering, biomaterials science, cell biology, physics, mathematics, and medicine. So we need to be a little more patient.

The main thing is to know that those who work in the field, doctors and engineers, programmers and scientists are making progress every day both in bioprinting technology itself and in understanding how it can be used and improved. Although we are not quite there yet, there is no doubt that medicine will be very different in 10-20 years, thanks also to bioprinting.

In brief

Bioprinting is an extension of traditional 3D printing.

Bioprinting can produce living tissue, bones, blood vessels, and possibly entire organs for use in medical procedures, medical training, and testing.

The cellular complexity of a living organism has made 3D bioprinting slower to develop than conventional 3D printing.

Bioprinting technology could enable the generation of patient-specific tissues to develop precise, targeted and fully personalized treatments.

We still have a long way to go before we can create fully functioning and viable organs for human transplantation.

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Cover photo: etonastenka, Depositphotos

When will we be able to print new organs on a 3D printer

Photo: Alexander Ryumin / TASS

Millions of people in the world are waiting for their turn for transplantation organs. In China alone, there are 1.5 million people on the waiting list, in the United States - 113 thousand, of which, on average, 20 people die a day without waiting for a donor. A new kidney - the most demanded organ - has to wait from three to five years. This problem can be solved by printing the necessary organs on special 3D printers.

True, not earlier than the next ten years.

Bioprinting technology: how and why are organs printed today?

(Video: RBC)

The principle is about the same as in conventional 3D printing: we get a three-dimensional object on a special printer.

The first stage is preprinting : first, a digital model of the future organ or tissue is created. For this, images obtained on MRI or CT are used.

Then printed, layer by layer - this technology is called additive. Only instead of a conventional 3D printer, there is a special bioprinter, and instead of ink, there are biomaterials. These can be human stem cells, which in the body perform the role of any cells; porcine collagen protein or seaweed-based cell material.

If the cells are alive, they are biopsied and prepared in a bioreactor until they multiply by division to the desired number. During printing, the bioprinter polymerizes the cellular structure - that is, binds it with the help of ultraviolet light, heating or cooling. Cell layers are connected using a hydrogel - organic or artificial.

The resulting structure is then placed in a bio-environment where it "ripens" before being transplanted. This is the longest stage: it can last several weeks. During this time, the structure stabilizes, and the cells are ready to perform their functions.

Then the organ is transplanted and they monitor how it takes root.

Bioprinting: how living organs are printed on a 3D printer

(Video: RBC)

In addition to conventional additive bioprinters, there are other bioprinters. Some of them print collagen directly on an open wound: this way you can quickly build up new skin even in the field. In this case, the ripening (post-printing) step is skipped.

There are also printers that print in outer space, in zero gravity. In the future, they can be used on the ISS:

There are more than 100 companies in the world that produce bioprinters for 3D printing. 39% of them are in the USA, 35% are in Europe (of which more than half are in France and Germany), 17% are in Asia, 5% are in Latin America.

In Russia, bioprinters are produced by 3D Bioprinting Solutions, which is also engaged in research in the field of bioprinting.

The cheapest and most compact bioprinter - Tissue Scribe from American 3D Cultures, costs from $1.5 thousand

In second place - Australian Rastrum from Inventia for $5 thousand

Aether bioprinter from the USA can be bought from $9 thousand

The middle segment - from $10 thousand and more - is represented by Bio X from CELLINK (Sweden), Regemat 3D of the Spanish RX1 and Canadian Aspect Biosystems.

3D Bioplotters from the German EnvisionTEC cost from $100,000, and the Russian FABION (3D Bioprinting Solutions) is even more expensive.

Finally, the most expensive bioprinters — more than $200,000 — are NovoGen MMX from Organovo (USA) and NGB-R from Poietis (France).

In addition to the cost of the printer, the printing process itself is an additional 15-20% of the cost of the entire project. It will cost even more to obtain the necessary cell material.

So far, the most successful experience has been the transplantation of cartilage - the very ears of Chinese children.

Small artificial cell bones are printed on a printer and then coated with a layer. They are planned to be transplanted instead of a broken or damaged area, after which they completely regenerate in three months. In the future, they want to use the technology for spinal injuries.

The most promising direction is 3D printing of leather. Already in five years they promise that this can be done directly on a person, over or instead of the damaged area. Skin and other tissues are being printed from cells from cancer patients to test various therapies.

More complex organs, such as kidneys or hearts, have so far only been printed as prototypes or transplanted into mice, not humans.

In order for the organs to take root and function well in the human body, they take the patient's cells, and then they divide until they are enough for printing. There are entire institutes that create cell lines for bioprinting. But the problem is that cells have a division limit, after which they are no longer usable. Therefore, it is possible to print a model of the heart, but not life-size - that is, it is not suitable for transplantation to a person.

The second problem is that the printed organ must function in conjunction with the rest of the body : digest food, secrete hormones, deliver blood and oxygen. A complex system of cells, tissues, nerves and blood vessels is responsible for all this.