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An Inside Look into the ACES Lab (Part II: TRICEP)

After peeking into some of the research labs at the ARC Centre of Excellence for Electromaterials Science (ACES), located at the Intelligent Polymer Research Institute (IPRI) in Australia’s University of Wollongong (UOW) Innovation Campus, thanks to a virtual tour by Gordon Wallace, Executive Director of ACES, audiences were able to get a first-hand look into another building at UOW. In the second part of the tour, Wallace showed the recently inaugurated Translational Research Initiative for Cell Engineering and Printing (TRICEP) and how it is leading the initiative for 3D bioprinting, encompassing bioinks, bioprinters, and bioprinting process developments, including the manufacturing of medical devices and the integration of living cells delivered using customized bioprinters to address specific medical challenges, and ultimately how they will scale up production of each of this innovations.

At TRICEP, scientists are using fundamental advances in materials science and engineering to solve real applications. The new facility was created last year to translate the advances into a manufacturable prototype or commercial product.

During this second part of the tour, Wallace explored the development of bioinks and bioprinters that will be commercially manufactured in the future, which is why the focus is more on material applications and protocol development for the manufacture of the bioinks and customized printers. A big part of what the researchers do involves exciting new developments to address very critical medical challenges, which in turn, create a commercial opportunity, according to Wallace.

“This is a great facility that incorporates the development of bioprinters, something you won’t find in a conventional university research environment, and we are taking all those 3D printing processes and making them ready for manufacture by implementing a quality management system that alows us to reallize real commercial opportunities,” suggested Wallace.

BIOINKS

The fundamental formulation for the bioinks developed come from the IPRI lab (as seen in the first part of the virtual tour), and TRICEP researchers need to use the new facility to scale it up and make it into a reliable product, but now without some challenges. Alexander Martyn, a Synthesis and Fabrication Chemist at TRICEP, is leading the bioink revolution and said: “Everything related to upscaling is a lot different here because we have to explore every single parameter of the experiments so that when we make the larger batches of bioink, they are reliable.”

“We usually need to go back to the source of the material. For some of the research work, small scale is easy to achieve, but here you need to know the primary source of the material to ensure quality control. Before we start making a large scale production of the bioink we have to undergo a suite of characterization to determine a high purity, which basically means determining if it is a very good product for us to work with. So first we would characterize the material to ensure the qualities and then we turn it into the bioink,” said Martyn.

Alexander Martyn showing how the 10-liter reactor works

“We start with small scale reactions, that give us between 20 and 50 grams in scale, much more than the one gram that is used for research. And then we turn to our bioreactors, one of them is a 10-liter reactor, capable of generating quantities of upto 500 grams. It is controlled by a thermoregulation unit plummerd throug the external wallls, so that we can control the temperature and collect the material. We also have a 20 litre reactor, capable of producing kilogram batches, which is the big leap into an industrial process,” he went on.

PRINTING PRINTERS

At TRICEP, researchers are using conventional 3D printers to create a range of customized 3D printers which help them address important research challenges in the medical spheres and built new tools to train the next generation of biofabricators.

Stephen Beirne, Additive Fabrication Capabilities Head at TRICEP, explained that “one of our capabilities includes printing printers. We have a range of additive fabrication tools and have recently been able to expand, even more, acquiring a Mimaki 3D printer that allows us attain components in full-colour representations, that gives more detail so that our collaborators and commercial partners get real realizations on the parts they want to produce. Overall, these systems enable us to print new components for new printing systems.”

TRICEP is a 100 percent owned University of Wollongong initiative that draws on expertise and facilities available within ACES and the Australian National Fabrication Facility (ANFF) Materials Node, both based at the UOW Innovation Campus. It houses a range of additive manufacturing technologies, including the highest resolution metal printer in Australia and the country’s leading biofabrication capability to develop biomaterials, with teams producing specialized 3D printing devices and customized bioinks to treat specific medical conditions, such as wound healing and artificial skin for burn victims.

Scaling manufacture of 3D bioprinters (Image credit: TRICEP)

TRICEP can commercialize opportunities in 3D bioprinting including printer manufacturing, biomaterials, bioinks, and material-cellular combinations to address significant industry challenges that require an exclusive, tailored solution, bringing to life novel technology from concept stage through to prototyping and manufacture of hardware and the formulation of customized bioinks to accelerate product development and rapidly decrease time to market.

Professionals at the TRICEP facility are creating and developing prototypes, making sure that these are ready to be manufactured at scale. Instead of making devices and integrating those into commercial type platforms, they are developing their own customized platforms for clinical challenges at hand, that allow for additional functionalities, such as to incorporate additional extruder or deposition techniques simultaneously as well as cross-linking methods.

For example, they are developing a series of handheld devices that are ideal for practical use in a clinical environment. Beirne described that “to characterize the device as we are going into our experimental protocols it is ideal to be able to transfer our mounting system into a tri-axis stage or even a five-axis stage, to have fine control over the scaffold and structures that we produce, to then be able to determine the repeatability and the consistency of the printing system we have developed.”

And the best part is, they have a whole suite of these, like the iFix pen, a cornea-correcting device created in collaboration with ACES at UOW. Beirne uses metal additive fabrication, basically, two selective laser melting systems, the first has a cylindrical build volume with a maximum built height of 74 mm (probably Trumpf or Sisma), while the newest and most recent system they added to the facility is a Concept Laser that allows printing volumes of 100mm x 100mm x 100 mm. They can also print in a range of different metals, like stainless steel and titanium, allowing for high resolution, low surface roughness components that are ideal for customized prototypes. He said that some of these structures are difficult to make with conventional manufacture devices.

“Some of the printers we created have also become educational printers and are an important part of our online teaching program. We have a graduate certificate on biofabrication which is available now, and that is the course work necessary to move to to the masters of biofabrication and it is exposure to this type of printers that give high level and state-of-the-art training in 3D printing. So that our prospective engineers and bioengineers have a range of tools and capabilities for them to learn, from the fundamentals of the 3D positioning systems all the way to the development of the mechanical extrusion mechanism and temperature management to allow them to see what happens to different materials and temperature conditions, printing conditions or extrusion parameters,” said Wallace.

Researcher working at the lab (Image credit: TRICEP)

One last customized printer to look at during the tour is 3D Alek, the bioprinter that replicates human ears for patients with microtia, built in collaboration with Payal Mukherjee, a nose and throat surgeon and Associate Professor at the University of Sydney School of Medicine. All of the components were built at the facility and it is able to print three different materials, each having their individual printing speed and condition.

The in-house ability of TRICEP researchers to develop both customized hardware and bioinks, as well as the growing clinical network, makes them uniquely placed to help companies create a complete end product that is tailor-made to combat a specific medical challenge. In addition, their extensive medical network throughout Australia helps them develop clinically relevant systems and protocols.

“All the projects are driven by real clinical needs, we are very fond of working with clinicians around the country who are really defining the challenges with us, and implementing a plan with us, and then helping us in terms of translation,” said Wallace.

You can tune in to see the second part of the virtual lab tour here.

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Envisiontec 3D-Bioplotter: New Bioprinting Capabilities

The 3D-Bioplotter from EnvisionTEC has been at the heart of over 333 scientific papers, from 3D printing human tissue to 3D printing an ovary for mouse implantation. It is one of the most commonly used (and earliest) 3D bioprinters in the industry for tissue engineering and biofabrication research.

Now, the global provider of professional-grade 3D printing solutions is expanding the bioprinting capabilities of their star product just in time for the European Society for Biomaterials (ESB) Annual Conference in Dresden, Germany. Launched in 2000, the 3D-Bioplotter is probably one of the most seasoned bioprinters in the market, and now it’s getting two new print head options that will help advance biomaterial research.

Researcher using EnvisionTEC 3D-Bioplotter

The first is an upgrade of the Photo-Curing head, now allowing up to five wavelengths or combinations thereof during one project. The second is an Ink-Jet Low-Temperature head designed to dispense materials through a non-contact process.

One of the several solidification processes available to 3D-Bioplotter customers is photo-curing. According to EnvisionTEC, while the wavelength of 365 nanometers (nm) remains the most commonly required by photoinitiators used by academic and industrial users, this wavelength has a negative impact on cell survivability during prolonged or repeated use, especially in the research field of bioprinting.

Therefore, the company sought out a way to solve this need to shift towards photoinitiators that react to the visible light range, to which cells can be exposed to with minimal biological effect.

To avoid the constant manual exchange of light sources when using different materials, as well as to allow combinations of photoinitiators, EnvisionTEC came up with an upgrade for their machine, a multi-wavelength pen upgrade which now provides five wavelengths into one single source pen. Through the 3D-Bioplotter software, individual wavelengths, or combinations thereof, are user-selectable and can be assigned to individual parts.

Current customers with existing photo-curing heads can have their existing heads upgraded to allow the use of the new source pens. The wavelengths included are 365, 385, 395, 405 and 455 nm.

The firm’s second highlight, the Ink-Jet Low-Temperature head, is aimed at dispensing low viscosity hydrogels as coatings while 3D printing parts or for hybrid scaffold fabrication. The key is that the built-in microdispensing valve can be controlled through the software to dispense individual, unconnected dots of material, or to connect them into lines of dispensed droplets.

With a 100 micron aperture, this head is restricted to low viscosity materials, such as hydrogels. Additionally, all components in contact with the dispensing material can be autoclaved, allowing for cell-suspensions to be dispensed as well. And depending on the choice of materials, the Ink-Jet head can be used to create fast dot printing projects, to dispense materials in specific positions on the platform (organ-on-a-chip projects), to fill pores in hybrid scaffolds, or to dispense coatings onto simultaneously printed 3D scaffolds.

EnvisionTEC states that the whole cartridge mount is heatable, from a room temperature range of up to 70 degrees centigrades, in order to keep the materials in the cartridge at their proper processing temperatures. Also, this head was designed to use 10 ml cartridges but also fits 3 ml disposable cartridges, with a dispensing duration of between 0.4 ms to 100 ms, and a frequency range of 1-100 Hz.

The 3D-Bioplotter

The 3D-Bioplotter family of printers consists of three models: the Starter series, the Developer series and the Manufacturer series, each with increasing capabilities. The original 3D-Bioplotter is now in its fourth generation, and more than 15 years of hardware and software development have gone into it.

One of the frequent users of the 3D-Bioplotter, Teja Guda, Assistant Professor of Biomedical Engineering at the University of Texas at San Antonio, said recently that “what’s so unique about the printer is that it is capable of printing living cells within the material as you print it.”

The modular 3D printer is easy to use while being capable of advanced research at the same time. The Bioplotter series prints with open-source biomaterials, using air or mechanical pressure to extrude them through a variety of syringes. Both new heads are currently on display in Dresden, at the EnvisionTEC booth, where attendees can see them in action and learn more about the research these new additions will make possible.

[Images: EnvisionTEC]

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Poietis: Bioprinting With Their Innovative Laser-Assisted Technology

In 2014, French startup Poietis developed a unique technology for the bioprinting of living tissue. Unlike conventional approaches to tissue engineering or extrusion bioprinting, their promising 4D laser-assisted system allows cells to be positioned in three dimensions with micrometric resolution and precision. Their aim is to design living tissue using cells and biomaterial that researchers can apply to manufacture products for regenerative medicine, preclinical research, and cosmetic uses–making a big difference in the testing of cosmetics and consumer products. This is especially relevant considering that the debate about animal research and testing is a hot topic everywhere.

In 2013, the European Union passed legislation that instituted a ban on the sale of animal-tested products in the continent, followed by other countries like India, Israel, Norway, Taiwan, and New Zealand, while the practice is being contested in the US and other markets where it is still legal. Companies like Poietis are using 3D bioprinting technology to develop a more cost-effective, versatile, and ethical way for companies to go about testing. But that’s just one of their advantages, along with the development of the multimodal bioprinting platform Next Generation Bioprinting (NGB); the creation of Poieskin, commercial bioprinted human tissue; and the NGB-C system for clinical applications.

Researcher at work at Poietis labs

In 2012 and after 20 years of professional experience in the biotech MedTech sector, the co-founder of Poietis, Bruno Brisson, met Fabien Guillemot (the other co-founder of the company and CEO).

“Guillemot was questioning himself about the valorization of a technology he had developed with his team at INSERM and the Tissue Bioengineering Lab of the University of Bordeaux: laser-assisted bioprinting, and I had created a consulting firm focused on business development in life sciences, so it was the right time to get together and share our vision of what could be done with this technology and what we wanted to do in the future,” revealed Brisson in an interview with 3DPrint.com. “We wanted to set-up an innovative company that could take the technology to clinics, provide new therapeutic solutions to the market of tissue and organ repairs, and help develop new advanced therapies.”

Bruno Brisson, Co-Founder of Poietis

Regulatory pressure everywhere to ban animal testing and concerns about animal experiments to model human health, along with the animal experiment ban for the cosmetics industry in Europe, has resulted in an evergrowing demand for in vitro alternatives. This is one of the reasons why Poeitis founders decided to first focus on in vitro applications for the skin tissue market. To do so, they hired an interdisciplinary team of physicists, software developers, biologists, and pharmacists to bring their expertise to the areas of laser and optics, microfluidics, machine learning, cell biology, and tissue engineering as well as cell therapy manufacturing. Their bioprinted in vitro models are used in dermo-cosmetics, but also in pharmaceutical research, for example, to evaluate the mechanism of actions for validating new drug candidates in the case of disease models.

The company, headquartered in Pessac, France, soon developed partnerships with other firms. In 2015, chemical giant BASF signed an agreement with Poietis to 3D print skin for cosmetic testing purposes, using the 3D laser-assisted bioprinting technology to further develop its Mimeskin tissue, which is one of the closest equivalents to the original physiological equivalents of real human skin. After their success, they moved towards improving the skin models by increasing structure complexity and adding new cell types. Almost around the same time, Poietis became associated with the L’Oréal group and began researching how to bioprint hair as a viable solution for people suffering from alopecia.

“Poietis has been able to enter into industrial partnerships quickly after inception, like with pharma company Servier to develop a 4D bioprinted liver model that could predict liver toxicity of drugs better than current methods,” Brisson said. “As well as other collaborations with the academic sector, such as with the Catholic University of Leuven (KU Leuven), in Belgium, on cartilage. As well as through two European Consortium EU H2020 FET-Open Pan3DP projects, one to biomimic developmental processes to fabricate 3D bioprinted pancreatic tissue units that allow sustained cell viability, expansion and functional differentiation ex vivo and another in neurobiology.”

A 16 layer 3D structure designed with Poietis CAD software and created with the NGB-R’s extrusion process

At Poietis, the core of their expertise is the high-resolution laser-assisted bioprinting, after which they have based and developed their Next-Generation Bioprinting (NGB) platform, which they claim gives tissue engineers and researchers greater freedom in the choice of biomaterials and hydrogels, and greater versatility in their research and development. The two bioprinters currently marketed are the NGB-R Bioprinter (commercialized for research applications) and the NGB-C Bioprinter (a clinical-grade, GMP-compliant system dedicated to clinical applications and challenges of industrial manufacturing of implantable tissues).

“Today our NGB-R consists of a platform (CAD + bioprinter) allowing to control the 3D organization of cells with cell resolution. It is an automated, robotized bio-printing platform guaranteeing reproducible tissue manufacturing and accelerating translation to clinical phases. Moreover, it is a single multimodal platform embedding the three main bioprinting technologies–including laser-assisted bioprinting– and allowing researchers to work with a variety of cell types but also to assess the printability and biocompatibility and work with a number of bioinks. Finally, we can control and monitor the formation of organoids through a controlled deposition of 2D cells (one or more cell types) and bioprint large objects such as cell aggregate of spheroids,” said Brisson.

At Poietis, they talk about the process as a form of 4D printing, claiming that “the approach consists in programming self-organized tissue (cells and extracellular matrix) that evolve in a controlled way until specific biological functions emerge”. So that by analyzing tissue evolution during maturation, they are able to optimize the initial tissue architecture defined by a CAD tool in order to improve the functionality of the printed tissues and guarantee that they are manufactured in the most reliable way. The company is developing dedicated software to program tissue self-organization, which means that they will anticipate the evolution of the bioprinted construct with time. And time plays a big role in 4D bioprinting, something which makes their system quite unique.

We have talked about 4D printing before, which means creating 3D objects that change their shape over time in response to stimuli such as heat, moisture or light, making structures that easily adapt to their environment. On the hardware side, Poietis applies its laser-assisted bioprinting technique using laser pulses programmed to be sent every nanosecond, used to deposit microscopic droplets of cell-laden ink on a cartridge (composed of an ink film spread on a glass plate). Via the software, they can control the physical conditions of the ejection (like energy and viscosity), as well as the droplet volume to near picolitre accuracy. According to the company, the process can achieve 20 µm resolution at speeds of 10,000 droplets a second, resulting in cell concentrations of 100 million cells/mL and 100 percent cell viability.

The process led Poietis to develop Poieskin, a bioprinted skin made up of a human full-thickness skin model that is entirely produced by 3D bioprinting.

“Poieskin® consists of a dermal compartment composed of primary human fibroblasts embedded in a collagen I matrix overlaid by a stratified epidermis derived from primary human keratinocytes. Its biofabrication benefits from the latest advances in 3D bioprinting technology. The high precision and resolution of Poietis laser-assisted bioprinter, as well as the embedded in-line monitoring systems, able to control the quality of each bioprinted layer and hence to manufacture controlled 3D cell structures and reproducible tissue models. It can be used for pharmacological and cosmetic research (like testing the effects of a drug on a real human skin equivalent), so at the moment, we are mainly selling the innovation to CROs (Contract Research Organisations), academic laboratories and dermo-cosmetic firms.”

With a tissue engineering market worth an estimated 15 billion dollars, and growing, the bioprinting industry is getting a lot of attention, and companies all over the world are taking notice. Poietis has three patents covering its bioprinting technology, and a recent financing round of five million euros to accelerate technological developments that could lead to the first implantation of a bioprinted tissue into patients starting in 2021, and is well is on its way to becoming one of the innovative European startups to look for during the coming years.

Brisson explained that “the future of tissue engineering will be based on technologies capable of studying the growth of connective tissue or organs but also to produce replacement tissue for implantation into the body. We consider that tissue engineering will be the next revolution in healthcare, using the patient’s own cells to build or rebuild organs.”

At the lab with Poietis

“Poietis is still working a lot on skin bioprinting, especially for in vitro applications based on Poieskin® as a platform of complexification. But the company is also developing the NGB-C system to meet future clinical needs of our partners, which is based on the same core technology as NGB-R, but NGB-C will face the requirements of translational research and the challenges associated with the industrial manufacturing of implantable tissues. Right now we are at a turning point as we started different projects with clinical aims, the first and most advanced is on the skin by targeting certain wound indications with a goal of a first-in-man within two years (clinical trials). We also have two other projects in cardiology and for all of these, we already have clinical collaborators.”

NGB-C System

The bioprinting technology available at Poietis is the result of innovative research, and over a ten-year time lapse at Inserm and the University of Bordeaux, resulting in wins at the iLab competition in 2014, the World Innovation Challenge Phase II in 2017, and most recently the EY Disruptive Strategy Award. But Poietis is lucky to be among a forward-looking bioprinting environment. The groundbreaking technology has seen some challenges over the last few years, and not every country has made efforts to help with its development.

According to Brisson, “France is certainly helping the emergence of these technologies with agencies such as BpiFrance, the French Public Investment Bank and a one-stop-shop for entrepreneurs and different subsidies for innovation at regional and national levels. That being said initiatives at the European level will certainly have a bigger impact, such as Restore–a very large action for advanced therapies at the EU level–, as well as the support of the European Medicines Agency.”

In many ways, Poietis has begun to change the future of regenerative medicine and the manufacture of living tissue. With uses in cosmetics and drug testing that are quickly becoming an alternative to animal testing everywhere, the company is fast to becoming a household name in France, pushing the advances of their innovation into clinical labs and giving researchers more tools to efficiently surpass the limits of bioprinting. We’ll have to wait until 2021 before the first implantation of bioprinted tissue into patients become a reality.

The post Poietis: Bioprinting With Their Innovative Laser-Assisted Technology appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

3D Printing Industry Experts Interview With Ricky Solorzano Co-Founder and CEO of Allevi

Ricky Solorzano

Ricky Solorzano is the Co-Founder and CEO of Allevi. Ricky is looking to combining IoT, organ engineering, and 3D Printing to bring bioprinting solutions to the World, Space, and Beyond. Allevi, Inc. believes 3D tissues will have a huge impact on humanity and create an entire new industry. They want to help scientists create more accurate hearts, lungs, and even brains in the lab. Users are automating the creation of tumor models, printing vasculature within 3D gels, and achieving physiological markers unseen before in tissues.

Explain how you got to your current state in life?

Following my passion got me to this point. It was really about pursuing tissue engineering and thinking it had the possibility to change the world. At first I thought about medical school, but then I had a chance to start a company which was really cool.

What is your educational background?

I went to bioengineering school and worked in a tissue lab. I learned about geometry and how tissue engineering is important. I also took an entrepreneurship class in college. It opened my eyes to different ways one can affect the world around me.

Are startups on the cutting edge vs universities?

Our value is giving the scientist the ability to execute the idea. It is important for us to give people value and for them to bring theirs. It’s the combination of this co-creation that really pushes the fields forward.

What is your value proposition?

We are able to have a lot of power go into a bioprinter. We make them very friendly and easy to use still. We are abstracting the complexity of a bioprinter to simplicity.

Allevi

What are future thoughts on this industry?

More and more tissues will be in the drug testing space. There will be more and more adoptions in investigative PIs (private investigators) to have a bioprinter within their labs. More companies will realize that it is important to have one in their labs. It is important to apply geometry to biology.

A lot of people within the industry of bioprinting are focusing on the importance of geometry applied to biology. Could you explain this a bit more?

Hearts need to be aligned. Shapes need to be consistent when created. It causes an organ or body part to be functional or not. Without geometric properties being maintained, parts will not work as efficiently as they could.

What would you do outside of this if you were not running Allevi?

Tissue engineering product development is probably where I would be. Being able to commercialize things is great way to make an impact. I have been able to learn this really well and continue.

Allevi Dual Extruder

What skills should people be looking into to be in this industry?

Be passionate about a specific direction. If you are passionate about using a bioprinter, work as a bioengineer. It is really important to have a skill set within biology and biomaterials. I think every field can contribute, it just matters what makes you personally excited.

What is the toughest obstacle in terms of work?

Discovery and where do we go. It is hard to figure out what the next step is. We do not have a clear guidance on what to do. It is important to understand the industry as a whole and where it is progressing.

Haifa: Technion Opens Center Dedicated to Bioprinting

Bioprinting is one of the hottest forms of 3D printing today, and with good reason, as it offers substantial impacts in the field of medicine. Now, the Technion-Israel Institute of Technology has built an entire center dedicated to bioprinting cells and tissues, recently inaugurated in the Faculty of Biomedical Engineering in Haifa.

The head of the center is Professor Shulamit Levenberg, also the faculty dean. Levenberg states that this new center of innovation—expected to propel the department into ‘new areas’— will be open to Technion scientists and researchers, along with others who are interested in using their new resources. Levenberg encourages individuals to use the lab because she understands that more projects within the center mean advancement for bioprinting overall.

Professor Shulamit Levenberg working in the lab.

While much about 3D printing is extremely creative, experimental, and even whimsical, the research studies emerging regarding bioprinting demonstrate the ability to cause significant and extremely positive change in medicine.

Their teams are currently developing ‘complex and precise artificial tissues that significantly improve their integration in the target organ.’ The Technion recognizes that scientists are showing ‘dizzying progress’ and their researchers are no exception, especially with the developing of new hardware that converts CT data into files for bioprinting.

“We have many sophisticated tissue printers at the Technion, but this a bioprinter that prints biomaterials and cells,” Levenberg said in a recent interview.

“The printer has different printing heads, each with a different feature such as temperature or UV light. The idea is that you can polymerize the bioink while you print,” she explains. “You start with liquid and while printing, you can solidify it in order to be able to make it a structure. So the material, the bio-ink, can be polymerized either by a change of temperature, UV light, light or by mixing different components,” she says.

Because the Technion offers such a strong emphasis on engineering, medicine, and life sciences, Levenberg sees the center as a logical addition that will allow their researchers to move forward significantly:

“I think it’s a very important step especially in the tissue engineering and biomaterial field because people now realize that the printers are important for engineering tissue for transplantation,” Levenberg says, adding that before they can fabricate organs, they first must master bioprinting tissue for implantation to replace damage.

So far, Levenberg has developed complex structures for bioprinting that are able to absorb into the host upon implantation. Her focus has been on finding the correct materials, in the form of bioink. There are several critical studies ongoing at Technion right now:

“We’re working on different types of tissues so we’re hoping for more results soon. For example we have a projects on developing tissues for bone and spinal cord repair, engineering muscle or pancreas tissues and also blood vessels.”

The term tissue engineering is just as important—and heavy hitting in the world of science today—as it sounds. Significant research is being performed toward the ultimate goal of 3D printing human organs, but along the way scientists have discovered many other important ways to bioprint. Many new methods and use of materials have the potential to change patient’s lives for the better, whether through 3D printed cardiac patches, progressive dental implants like alveolar ridge grafts, or bioprinted corneas.

Find out more about 3D printing and living cells here. What do you think of this news? Let us know your thoughts! Join the discussion of this and other 3D printing topics at 3DPrintBoard.com.

[Source / Images: nocamels]

Biodiscoveries: CELLINK is bioprinting its way into the future

Back in 2015, Erik Gatenholm realized there was no place to purchase bioink for 3D bioprinting. So, blown away by this gap in the market, he quickly worked with co-founder Hector Martinez to create a universal bioink that anyone working with bioprinting could use. It was quite a high stakes bet, and at the beginning they set up a webshop to see if they got any bites. It only took 24 hours for the first sale. With more orders quickly coming in, they realized the enormous potential of the product they developed, and CELLINK was born, becoming the first company to commercialize a universal bioink for bioprinting of human tissues and organs.

CELLINK co-founders Erik Gatenholm and Hector Martinez

In the United States alone, every 10 minutes another person is added to the growing waiting list for organ transplants, most of them (60%) in need of a kidney, and with over 130,000 organs transplanted every year worldwide, is no wonder how demand certainly outweighs supply almost everywhere. In some countries the wait can take years, making 3D printing of organs one of the most sought after technologies out there. Bioprinting in the future could allow patients and doctors to reduce waiting times, increase compatibility and decrease immunological failure. For this to happen medical researchers will need to design organs using modeling software, and then print them with biomaterials such as polymers and hydrogels, in addition to the patient’s own cells. Although currently focused on growing cartilage and skin cells suitable for testing drugs and cosmetics, the Swedish company founded in Gothenburg in 2016, hopes to progress the technology far enough to create replacement organs for transplant in humans in the next 15 years.

“In the coming decade we would like to continue to push the boundaries of 3D bioprinting until it becomes an established technology in the medical field. We have the vision of becoming the first and number one provider of bioprinters, bioinks, software and technical know-how for the next generation of medical device manufacturers,” co-founder and CTO Hector Martinez told 3DPrint.com.

Their unique bioink is a biomaterial innovation that allows human cells to grow and thrive as they would in circumstances close to their natural environment. The startup has already managed to print human skin and is also working on producing liver tissues, as well as the beta cells that produce the insulin we need to survive. In 2018 it began printing tumors to combat cancer as part of a research project that doesn’t endanger human lives, and just a few weeks ago, it teamed up with Volumetric to develop Lumen X, a digital light processing bioprinter, designed to enhance inventions in creating more substantial vascular structures. Skin care products, topological drugs and medical treatments are all in need of enhanced testing procedures that can increase the transability from in vitro testing to in vivo usage of products. With tissue engineering and 3D bioprinting more representative in vitro models can be constructed, limiting the use of testing in animals.

CELLINK’s bioinks

Actually, academic labs and companies worldwide are trying to bioengineer all kinds of sophisticated creations for regenerative medicine, drug testing, screening, and tissue engineering. So it’s no wonder CELLINK has their research team focused on creating the next generation of bioinks. Their top selling product is making bioprinting much easier than it used to be some 10 years ago, with 30 different types of bioink available, with prices that go from 99 to 900 dollars. So, what makes one bioink more expensive than the other? It’s all about the components. Collagen and laminin are more expensive to produce than gelatin, raising the price of the end-product. According to CELLINK, scientists mix their live cells into the company’s bioink, a kind of gel designed to allow cells to survive and multiply. The ink is then loaded into a 3D printer by the customer, which forms the desired shape layer by layer as the gel solidifies. By the time the lights inside CELLINK’s box turn green, researchers have an object that acts like human tissue, and can then apply their drug and see how the living cells inside respond.

CELLINK team printing liver models at the lab

“Today we are taking the necessary steps to build and expand our technology offering and exploring new methods for bioprinting tissues. Such technologies include multiple contact-less dispensing methods and light-based bioprinting techniques that enable the bioprinting of high resolution tissue constructs. Refining such technologies will take a close collaboration with our customers as we define the best practices for bioprinting different tissues and specific functions. We can already anticipate that the integration of different bioprinting technologies with post-bioprinting, real-time monitoring systems will be of utmost importance as the bioprinted tissue matures and attains a specific function through an active and precise manipulation of its environment.” Chief IT Officer Jockum Svanberg explained to 3DPrint.com.

Creating the raw material for bioprinting processes is no easy task. Cellink has been focusing on process-compatible soft biomaterials loaded with living cells to create its bioinks since September 2015. The process of bioprinting requires a delivery medium for cells which can be deposited into designed shapes acquired from computer-aided design (CAD) models, which can be generated using 3D medical images obtained through MRIs or CT scans. Some important features of an ideal bioink material are bioprintability, high mechanical integrity and stability, insolubility in cell culture medium, biodegradability at a rate appropriate to the regenerating tissue, non-toxicity and non-immunogenicity, and the ability to promote cell adhesion. Some bioink types, like hydorgels, are not always suitable as construction materials which is why CELLINK is working on a study to provide an upgraded version of the current CELLINK BONE bioink by incorporating collagen and hydroxyapatite. The bioink currently offered does not get close to the real stiffness of the natural bone tissue, but finely resembles its chemical composition. The advantage of such a soft material is to be able to incorporate cells and, during the bioprinting process, to locate them at a precise position throughout the scaffold. This is still for research use only and might take a few years until it is compatible for human use.

With CELLINK bioinks, 3D bioprinting of tissues will help hasten bone fracture healing

Since its start the technology firm has grown to become one of the big competitors in the industry. CELLINK had only been in existence for ten months before they decided to pursue their IPO in November of 2016, listing on Nasdaq First North after a 1070% oversubscribed IPO, which means that demand for their shares was ten times what they expected. Since then, shares have risen over 400%, giving the company a present-day market cap of around $257 million. CELLINK’s affordable printers have already been bought by customers in 25 countries around the world, mostly universities, like Stanford, Harvard, Yale, Princeton and MIT, and some private customers, including Shiseido, Roche, Merck, Johnson and Johnson, and Toyota

But it’s not just about bioprinting it’s way into the future of medicine, CELLINK is also working with other disruptive technologies, such as machine learning. CELLINK told 3DPrint.com that “they want to empower our users with better tools to simplify the bioprinting learning process and broaden its adoption”. One example of this is by developing algorithms that analyse printed structures and based on the results can recommend printing parameters to the users. Using this tool in the development, has helped them speed up the bioink development process. They have just launched a new product: CELLCYTE X, a live cell imaging microscope with live monitoring and analysis of cells in the cloud. Traditionally cell studies have involved manual labor and relied on analysis of the images from an expert, but using deep learning models they are automating this process to provide better and more reliable analysis to their users. The system relies on the latest in serverless system architecture to provide the most scalable, reliable and most intuitive system on the market.

What do you think, will CELLINK continue its upward trajectory? Will it become superseded by other larger firms or get passed by newer start ups? Find out more through our series of articles exploring bioprinting, Biodiscoveries.