Bio 3d printing stocks

Bioprinting Stocks: 3D Systems and Desktop Metal

In the 3D printing world, 2021 is shaping up to be the year of bioprinting, with both 3D Systems (DDD -4.22%) and Desktop Metal (DM -7.66%) entering the commercial bioprinting market this year.

Bioprinting refers to using "bioinks" made of various biocompatible materials (some of which contain human or animal cells) to print three-dimensional, functional tissue. Current and potential future applications of the rapidly developing technology include accelerating the drug discovery process, producing body parts such as bones and soft tissue, and -- the ultimate goal -- producing solid organs for human transplantation.

Of course, neither 3D Systems nor Desktop Metal is anywhere close to a pure play on bioprinting, but they're in the market now, and that could prove to be a very good thing for their future performance.

Image source: Getty Images.

Bioprinting players: Overview

Company	Market Cap	Wall Street's Projected 5-Year Annualized EPS Growth	Year-To-Date 2020 Return (Decline)	5-Year Return
3D Systems	$4. 8 billion	10%	275%	203%
Desktop Metal	$3.3 billion	N/A	(30.2%)	N/A
S&P 500	--	--	14.8%	131%

Data source: YCharts. Data to June 25, 2021.

3D Systems

3D Systems, which is the largest pure-play 3D printing company by revenue and market cap, was profitable in the first quarter of 2021 from both an adjusted basis and under generally accepted accounting principles (GAAP). And Wall Street is projecting the company will be profitable, at least when adjusted for one-time items, for full-year 2021.

3D Systems first dived into bioprinting in 2017 through a research collaboration with United Therapeutics (UTHR 1.25%), a U.S.-based biotech company. The companies are working toward producing solid organs for human transplants. There is certainly no guarantee that anyone working toward this goal will be successful, though I do believe that eventually this momentous milestone will be achieved. Even if the 3D Systems-United Therapeutics partnership ultimately achieves its goal, any revenue from it will be many years away.

In May, 3D Systems made the leap into the commercial 3D printing market by acquiring Allevi (formerly BioBots), which sells bioprinters, bioinks, and related products to research entities around the world. The Philadelphia-based company is small but well regarded, or at least it was when I first wrote about it in 2015. Dun & Bradstreet estimates that Allevi's annual revenue is about $1.9 million. Currently, this business won't move the needle for 3D Systems, which has an annual revenue run rate of about $584 million. But it's a start upon which the company can build.

Last week brought news of another 3D Systems' bioprinting collaboration: The company is teaming with Israel-based CollPlant Biotechnologies (CLGN 3.29%) to use bioprinting to improve the solutions now available for breast reconstruction, a procedure many women choose to undergo following breast cancer. Once again, any possible revenue from this teaming is many years away.

Desktop Metal

That Desktop Metal, which joined the ranks of the publicly traded via a special acquisition company (SPAC) in December 2020, is now involved in bioprinting seems to fly under the radar of many investors.

The company -- which is not profitable and probably won't be for some time -- entered the commercial bioprinting realm in the same way as 3D Systems: via an acquisition. In February, Desktop Metal bought Germany-based EnvisionTEC, which is probably best known for its digital light processing (DLP) for polymers.

EnvisionTEC has also been a player in the bioprinting market for some time. Indeed, the company touts that its 3D-Bioplotter, launched in 2000, is "the most seasoned bioprinter in the market, backed by the most research." The company's bioprinters have been used to fabricate hyperelastic bone and ovary implants, according to its website. (ScienceDaily defines hyperelastic bone as a "3D-printed synthetic scaffold" designed "to support the growth and regeneration of new bone. ")

We have no idea as to the revenue EnvisionTec generates from sales of its three models of 3D-Bioplotters. For that matter, the same can be said about EnvisionTec's entire business. Desktop Metal didn't disclose EnvisionTec's revenue when it acquired the company or when it released its first-quarter results.

Investors will probably learn more about 3D Systems' and Desktop Metal's bioprinting activities when the companies release their second-quarter results, which will likely be in early or mid August.

Beth McKenna has no position in any of the stocks mentioned. The Motley Fool recommends 3D Systems. The Motley Fool has a disclosure policy.

5 3D Printing Stocks to Consider in 2022

An in-depth look at the leading 3D printing stocks in the U.S stock market this year. Here’s what you need to know.

By Nicholas Rossolillo – Updated Jul 11, 2022 at 2:42PM

Back in the early 2010s, stocks were booming for 3D printing -- also known as additive manufacturing, a computer-controlled process in which three-dimensional objects are made. But the boom was followed by a bust as many pure-play 3D printing companies didn't immediately deliver on lofty expectations.

Rumors of the manufacturing technology's demise are clearly premature. These days, 3D printing is a high-growth niche that is steadily reshaping the manufacturing and industrial sectors. Some estimates point to a doubling in annual revenue from additive manufacturing between 2022 and 2026. Even growth investor Cathie Wood has launched a fund focused on manufacturing tech, The 3D Printing ETF (NYSEMKT:PRNT), via her company ARK Invest.

Here's what you need to know about 3D printing and additive manufacturing stocks for 2022:

Image source: Getty Images.

Investing in 3D printing stocks

The manufacturing of products in all corners of the economy is being revolutionized by 3D printing, from healthcare equipment to metal fabrication to housing construction. It's invading so many sectors that tech giants such as Microsoft (NASDAQ:MSFT), Autodesk (NASDAQ:ADSK), and HP (NYSE:HPQ) have launched products aimed at 3D printing and additive manufacturing. Other engineering and software outfits such as Dassault Systemes (OTC:DASTY), ANSYS (NASDAQ:ANSS), and Trimble (NASDAQ:TRMB) have also gotten involved in 3D printing technology.

Here are five key players to consider for 2022 that are a more focused bet on 3D printing:

Data source: YCharts. Market cap as of April 19, 2022.
Company	Market Cap	Description
Desktop Metal (NYSE:DM)	$1.3 billion	Recent IPO that focuses on metal fabrication technology.
Stratasys (NASDAQ:SSYS)	$1.5 billion	One of the original 3D printing pioneers, with a wide array of printers and supporting design software.
Xometry (NASDAQ:XMTR)	$1.9 billion	A manufacturing marketplace, including access to on-demand 3D printing services.
3D Systems (NYSE:DDD)	$1.9 billion	Another original 3D printing pioneer and the largest pure-play stock on 3D printing technology.
PTC (NASDAQ:PTC)	$11.7 billion	A manufacturing technology provider with a suite of software and related services for industrial businesses.

1. Desktop Metal

This company is a recent entry into the 3D printing space after going public via a SPAC at the end of 2020. The stock has been a terrible market underperformer since then, losing three-quarters of its value as of spring 2022. However, Desktop Metal could still be a promising investment for the long term.

As its name implies, Desktop Metal develops 3D printing hardware and accompanying design software for metal and carbon fiber parts. The company's smaller systems can handle prototyping and one-off parts, and larger printers are production grade-designed for manufacturing facilities. Desktop Metal serves companies operating in automotive, consumer goods, and heavy industrial equipment businesses.

Despite a tenuous start as a public company, Desktop Metal was actually increasing revenue at a torrid triple-digit pace in 2021. Gross profit margins are thin, and the company generated a steep net loss, but that should improve over time as the business scales its operation. Desktop Metal also has several hundred million dollars in cash and investments to fund its expansion. It used some of these funds to acquire additive manufacturing peer ExOne at the end of 2021.

2. Stratasys

Stratasys was part of the early 2010s 3D printing stock boom and bust, but its business has endured. Sales took a dip early in the COVID-19 pandemic but are rebounding as the Israel-based company picks up new manufacturing contracts.

Stratasys serves a diverse set of customers, including aerospace and automotive parts manufacturers, medical and dental companies, and makers of basic consumer products. In addition to a wide array of 3D printer models, Stratasys develops software to help users accelerate the time between design and final printing.

It isn't the highest-growth name on this list, but Stratasys is profitable (on a free cash flow basis) and has more than $500 million in cash and investments on its balance sheet, as well as no debt. Management thinks its payoff from years of research and development into additive manufacturing will accelerate in 2022.

3. Xometry

This is another newcomer to public markets. Xometry completed its initial public offering (IPO) over the summer of 2021, raising almost $350 million in cash in the process. As is often the case with new IPOs, the stock has underperformed since then. It has lost over half of its value from the time it started trading on public markets, but the business itself is rapidly growing.

Xometry is a marketplace for on-demand manufacturing of prototyping and mass production. It has a network of more than 5,000 suppliers that companies can call on to meet their fabrication needs. Among the suppliers on the Xometry platform are 3D printing companies, injection molding, and automated machining. The company reported having more than 28,000 active buyers utilizing its platform at the end of 2021.

Although it isn't profitable yet, Xometry's unique approach to the 3D printing and additive manufacturing industry is growing fast. Like other names on this list, it has a sizable war chest of cash and short-term investments that it can spend on research and marketing as it tries to attract more suppliers and buyers to its marketplace.

4. 3D Systems

3D Systems was another early player in the 3D printing industry, and while it suffered through the boom-and-bust period of the early 2010s, its business has held steady for much of the past decade. After a brief dip during the early days of the pandemic, 3D Systems is back in growth mode.

The company develops printers and design software for all sorts of materials and industries (medical device makers, dental labs, semiconductor designers, aerospace, and automotive manufacturers). It claims leadership among independent 3D printing companies (as measured by sales). As the 3D printing industry expands in the coming years, 3D Systems thinks it will be able to attract lots of new business with its extensive experience and global reach.

As an established tech outfit in the manufacturing sector, 3D Systems offers investors the prospect of more stable growth, along with profitability. It also has a large net cash position from which it can consolidate its lead in 3D printers and software technology.

5. PTC

By far the largest company on this list, PTC is a longtime technology partner of manufacturing and industrial enterprises. Fast approaching $2 billion in annualized sales and highly profitable, PTC has all the tools needed to digitally transform industrial businesses.

Besides 3D printing computer-aided design software (ANSYS is a peer and software partner that also operates in this space), PTC specializes in augmented reality, industrial IoT (Internet of Things), and product life-cycle management software. Most of its revenue is subscription-based (including its Creo software that enables 3D printing), making for a stable and steadily growing business model that generates ample cash flow. PTC puts spare cash to work developing new products for its partners and makes bolt-on acquisitions of other software companies that enhance its overall portfolio.

As a larger company, PTC won't be the fastest-growing stock in the additive manufacturing and 3D printing space. However, the company has established itself as a leader in industrial technology and should be a primary beneficiary as the production of manufactured goods gets more efficient.

The future of 3D printing

Manufacturing technology is making inroads throughout the global economy by reducing the cost of production and localizing and speeding up the time it takes to deliver customer orders. This is far from mere hype. Nevertheless, as is the case with all technology investments, progress won't go straight up. Expect twists and turns in these stocks as they develop new methods to design and make products.

If you decide to invest, do so in a measured way. Maintain a diversified portfolio, be wary of stocks benefiting from investor over-optimism, and always leave spare cash to invest more when there are inevitable dips. Given enough time -- years and decades -- investing in 3D printing could eventually provide a big payoff.

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When will we be able to print new organs on a 3D printer? 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 they print, 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 biological environment where it "ripens" before transplanting. 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 3D bioprinters. 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 by American 3D Cultures, costs from $1.5 thousand

In second place - Australian Rastrum from Inventia for $5,000.

Aether bioprinter from the USA can be bought from $9,000. 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 into 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. So far, it has not been possible to reproduce it exactly.

Finally, bioprinting technologies are not yet regulated in any way. All research must go through all stages of testing, including on humans, and then obtaining patents.

So far, experts predict the introduction of technology not earlier than in 10-15 years. By then, bioprinters and cellular materials will be widely available, and even the most remote regions will be able to use bioprinting.

More to read:

History and technology of bioprinting (ENG)
Overview of the current state of bioprinting and major challenges
How bioprinting will change our lives (ENG)
Video: what the bioprinting process looks like (ENG)
Video: Graphic explaining the printing process from living cells (ENG)
Video: Ear 3D printing (ENG)

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Organ printing: how 3D bioprinting technologies have advanced and what hinders their development

Rusbase

November 12, 2019

The artificial creation of human skin, tissue and internal organs may sound like science fiction, but most of it is happening right now. 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.

Chitosan, a polysaccharide obtained from the external skeleton of mollusks (eg shrimp) or by fermenting fungi, is often used in bioprinting. 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 replacements at the Wake Forest University laboratory 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 sort 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 a bone transplant. 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:

“

“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 people.

If the 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 an entire 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 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

Around 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.