regenHU CEO: Bioprinting Will Strengthen OrganTrans Project to 3D Print Liver Organoid

The European consortium OrganTrans is preparing to develop a tissue engineering platform capable of generating liver tissue. The proposed automated and standardized disruptive alternative solution to organ donation for patients with liver disease will stand on 3D bioprinting know-how from Swiss biomedical firm regenHU. Coordinated by Swiss research and development center CSEM, the eight partners and two transplantation centers engaged in the consortium will be using regenHU’s 3D bioprinters to produce organoid-based liver constructs with organoid laden bioinks.

In April 2020, we reported that OrganTrans would tackle the important healthcare challenge of end-stage liver disease (ESLD) by capitalizing on advancements in the regenerative medicine field, like using biofabricated liver tissue, to develop an entire value chain from the cell source to tissue engineering, biofabrication, post-processing and testing, and liver transplantation under the “compassionate use exemption” regulation (which provides an important pathway for patients with life-threatening conditions to gain access to unproven human cells and tissue products). To understand the key role of biofabrication in this innovative project, 3DPrint.com asked regenHU’s new CEO, Simon MacKenzie, to tell us more about the challenges that lie ahead for the European consortium and his company.

regenHU CEO Simon MacKenzie (Image courtesy of regenHU)

The project officially began in January 2020, what can we expect when it ends in December 2022?

The current goal of this project is to create a functional biofabricated liver construct that can be implanted into a mouse model. I consider that the OrganTrans team will accelerate new solutions for patients with liver failure. It is challenging, but we do envision successful in vivo trials. Of course, this major achievement will not be the end of the story; significant work and research will still be required to transfer these results to human clinical trials. The major remaining challenges will probably be the process scale-up to produce larger tissue and regulatory aspects.

Will this research be groundbreaking to treat liver disease in the future?

Demonstrating the feasibility of the approach in a mouse model will be groundbreaking for the disease because it will demonstrate its potential as an alternative to transplantation. Diseases like NASH [nonalcoholic steatohepatitis, an aggressive form of fatty liver disease] are increasing dramatically, and likely to be a leading cause of death within the next few years. Moreover, the difficulty of detecting the disease until it is potentially too late leads to significant challenges for therapeutic intervention, meaning transplantation will remain the main option for severely affected patients. This well-recognized need, along with the lack of donor organs will ensure bioprinted livers will continue to be well funded. But the value of the project goes beyond liver disease, as the new technologies developed in the frame of OrganTrans will not be limited to liver applications. They relate to the challenges of biofabrication of any organoid-based tissue, which can potentially be beneficial for a large variety of indications.

Can you tell me more about the role of regenHU within the OrganTrans consortium?

Such a complex and ambitious endeavor needs very different and complementary knowledge and competences. Teamwork will be a central element, first to enable, then to accelerate, these new solutions. With this in mind, we have been reorganizing regenHU to bring better project collaborative capabilities to this project, and others like it that we are engaged in. regenHU is a pioneer and global leader in tissue and organ printing technologies converging digital manufacturing, biomaterials, and biotechnology to lead transformational innovations in healthcare. We focus on delivering advancements in the instruments and software required for tissue engineering, and our technology evolving along with the biological research of our partners. We, therefore, consider these partnerships with the scientific community critical for our development.

An outline of the OrganTrans project (Image courtesy of OrganTrans)

regenHU is one of the largest contributors to this project, is this part of the company’s commitment to regenerative medicine?

We can see the need for biotechnology solutions for a wide range of disease states. Our strengths are in engineering the instruments and software necessary to allow the producers of biomaterials and the suppliers of cells to combine their products to achieve functional tissues and organs. Our commitment is to provide disruptive technologies that will enable the community to make regenerative medicine a reality, with precision and reproducibility in mind, for today’s researchers and tomorrow’s industrial biofabrication needs. One of the key challenges is the current limitation in the scale and volume of bioprinting which is linked to the reproducibility of the print. To progress into the manufacture of medical products, bioprinters will need to operate at a scale beyond current capabilities. We design our instruments with these goals in mind and have assembled a team to solve the many challenges to achieve this.

How advanced is the bioprinting community in Europe?

The 3D bioprinting field is several years behind mainstream 3D printing, with the industrialization of the instruments, biomaterials, and cells required before bioprinting can progress to commercial-scale biofabrication. However, as with continued development seen in 3D printing, the technology convergence required for tissue and organ printing that changes medical treatments will become a reality through the efforts of engineering companies like regenHU, biomaterial developers, and human cell expansion technologies, being combined in projects such as OrganTrans.

As the newly appointed CEO of the company, how do you feel taking on this project?

Successfully entering the OrganTrans consortium is just one part of the company. regenHU investors see my arrival as the catalyst to bring regenHU to the next stage in its evolution. Our goal remains the production of industrial biofabrication instruments capable of delivering the medical potential of bioprinting, novel bioinks, and stem cells. To achieve this, we are enhancing the team and structure of the company, bringing forward the development of new technologies and increasing our global footprint to better support our collaborative partners. I have spent many years in regenerative medicine and pharma and can see the potential of bioprinting to revolutionize many areas of medical science, so joining regenHU was an easy choice. As CEO, my main role is to provide the right support structure to enable our entrepreneurial engineering teams to thrive and be brave enough to push boundaries. Additionally, as we cannot achieve our end goal on our own, I am here to nurture the important connections with our user community. Only by listening to their valuable insights and solving problems with them, we will push the technology onward.

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COVID-19: Ivaldi’s Nora Toure on 3D Printing and the Supply Chain

Last year, Nora Toure made a very interesting talk on the impact of 3D printing on the global supply chain. The topic was a prescient one, given the events to come in 2020. In turn, I have interviewed Toure about how the topic has evolved since the COVID-19 pandemic.

It’s been a year since you last gave your talk on how 3D printing will disrupt the global supply chain. Can you give a review of the supply chain and 3D printing between that talk and now?

A lot has happened since then, as far as implementing Ivaldi Group’s distributed manufacturing solution! Since my TEDx talk on disrupting supply chains with additive manufacturing, we’ve delivered the world’s first maritime spare parts on merchant vessels, we continued digitizing, optimizing and reviewing performance of thousands of spare parts, not only in maritime, but also in automotive, construction and mining.

The world’s first 3D-printed scupper plug.

I believe the adoption of additive manufacturing in supply chains optimization will be boosted in the next few months as heavy industries will go back to business and recover from the COVID-19 pandemic. The potential of additive manufacturing goes beyond technical comparison between materials and manufacturing process. Shipping, warehousing,  procurement, CO2 emissions, downtime are all savings that need to be taken into account when comparing current supply chain models to distributed manufacturing enhanced supply chains.

A closer look at the first 3D-printed scupper plug.

We have experienced COVID-19 the world over and it has almost completely changed the way we have been doing things. Have you noticed an impact on 3D printing in the global supply chain, particular as a disruptive technology?

As much as I’d rather COVID-19 wasn’t our new reality, I have to admit I’ve been impressed by our additive manufacturing community. It’s fantastic to see how we’ve organized ourselves in such a short amount of time. What strikes me the most is how fast individuals, but also companies of various sizes organize themselves and build their own supply chains, from designing and testing, producing, sanitizing and getting the PPE to the hospitals.

I see disruption of supply chains on two levels:

  1. Simplification of supply chains, with a more limited number of intermediaries and a collaborative approach in product sourcing and design are leading to efficient supply chains, even when triggered by individuals,

  2. Removing shipping from supply chains and focusing on sending files rather than physical products is not only fastening the entire process and saving on CO2 emissions, it’s also now proven that it’s improving efficiency all over

Interestingly, you are the founder and president of Women in 3D Printing. What role is your organization playing in 3D printing in the global supply chain, if any?

Since we do not provide parts nor any technology service, it was a bit challenging to see how we could contribute in manufacturing [personal protection equipment]. I was involved on a personal level in some local initiatives, but I wanted to keep Wi3DP agnostic because, again, we don’t have a full-time team nor employees we could dedicate to any project.

That being said, being a large community, we get information. So, our contribution has been to provide a directory of those 3D printing responses.

But I have to say, I am impressed with the work our ambassadors have done during this time, as many of them have been involved with local 3D printing responses to COVID-19.

How do you view the impact of 3D printing in the supply chain for developing nations, particularly in Africa?

Wherever supply chains aren’t fully developed and established, I believe there is an opportunity to adopt distributed manufacturing solutions sooner and implement those strategies faster.

Organizations such as 3DAfrica are doing a great job at enabling local businesses adopting 3D printing. This could be taken a step further with corporates adopting the technology as well.

Role of Additive Manufacturing in Supply Chain courtesy of Croftam UK.

What is your financial outlook for 3D printing in the supply chain in the next five years, especially after the effects of COVID-19. Do you see a rise in financial growth for 3D printing services in the supply chain or a drop?

The savings enabled by on-demand distributed manufacturing, enabled by 3D printing services, are so big and are impacting, from a financial point of view, more than unit parts cost comparison. The impact is the entire supply chain—on warehousing, shipping, delivery etc.—that it just makes sense to switch some of the traditionally sourced spare parts to additive manufacturing.

 

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RIZE Introduces Adaptive 2XC Desktop 3D Printer for Offices, Schools, and Homes

In 2016, Massachusetts-based 3D printing company RIZE Inc. released its first industrial-grade desktop 3D printer, the Rize One, renowned for its safety, low emissions, and elimination of post-processing. Then, in 2018, the company introduced the first industrial desktop AM solution for manufacturing full-color functional parts, the XRIZE system, which I was lucky enough to test out at RAPID 2019. Today, it’s announcing a new kind of desktop 3D printer, the professional RIZE 2XC, an adaptive system that was developed collaboratively with South Korean 3D printer manufacturer Sindoh.

I spoke with RIZE CEO Andy Kalambi ahead of the release, who told me that even during the ongoing COVID-19 pandemic, the company has been “very productive.”

“It’s been an interesting time, but rewarding,” Kalambi said.

He said that the RIZE team speaks every morning during a check-in meeting, to make sure everyone is doing okay and see if anyone needs help with a project. Even during lockdowns across the US, the company has been busy, 3D printing personalized face shields that were distributed to hundreds of essential and healthcare works in the Boston area and working on the new 2XC.

“Entirely during COVID times, we developed this new printer with Sindoh,” he told me.

The RIZE 2XC was engineered from home offices, and, according to a RIZE press release, is a testament “to the safety principles embodied in RIZE’s solutions – principles that are especially relevant today as organizations reinvent workflows for a return to office locations.” The business supply chain needs to be even more flexible now due to COVID, and RIZE says its new printer can help. The 2XC can be used at home – no need to worry about germs spreading from lack of social distancing – and in offices and classrooms, with no fear of releasing harmful airborne volatile organic compounds (VOCs).

“The newer, higher performance, safe materials from next-gen FFF players such as RIZE are helping to drive a transformation in the 3D printing sector that are particularly relevant now as the world emerges from a pandemic. The durability and safety advantage that’s possible from next-generation 3D printing systems merits the attention of any engineering or design team that wants to give their users the best, and safest, tools,” Tim Greene, research director, 3D printing, for IDC said in the release.

The adaptive printer is the first deliverable to come from the RIZIUM Alliance, which is a new collaboration between RIZE and industry partners, like Sindoh, to drive safer, more sustainable 3D printing. The RIZE 2XC was made with a redesigned Sindoh dual-extrusion 3D printer, which can run engineering-grade RIZIUM materials that are moisture-resistant, recyclable, and zero emission.

RIZIUM One material

“We based our material on safety – it’s engineered for safety, durability, and strength,” Kalambi told me. “They’re medical grade, and especially in today’s context, things like sanitizing and being able to wash it with alcohol or acetone is important. Materials science is our differentiating factor.”

Kalambi told me that the ‘C’ in the company’s new 2XC printer stands for ‘composite,’ since RIZE takes a “material-led approach.”

“What we have done now is taken our material portfolio and partnered with industrial players, so we can offer it to a broader market of users.”

Sindoh is applying the innovative RIZIUM materials, engineered for user health, so that customers in various sectors on its platform can use a safe, sustainable material at a lower price.

“With Sindoh, we’re working with the same materials,” Kalambi explained. “We have done lots of engineering efforts with them to get the printer ready for our materials, worked on nozzles and the drive train and the slicer, all of that, and made the printer far more robust. It’s a printer that is a joint product. It’s a new hybrid platform, releasing a set of products with Sindoh that’s based on our polymers and materials science.”

The two independent extruders on the RIZE 2XC are designed for composite filaments and hardened materials. One extruder runs RIZIUM polymers and composites, which can be washed with just soap and water, while the other runs the unique RIZIUM Support, created by RIZE specifically for filament-based extrusion 3D printers. All in all, RIZE says that its new printer offers a safe way to fabricate durable, strong, functional components, without any unnecessary post-processing.

“The RIZE 2XC is especially well-suited for a variety of Industrial and Academic applications,” Ricco Busk, Director at RIZE partner CADSYS, stated. “Given the high demand for having 3D Composite Parts, we are able to, almost immediately, sign up a customer for the RIZE 2XC to use in their innovative plastic molding applications, such as robotic grippers. Combining RIZE’s material advantage in the high quality, easy to use 2XC 3D platform opens doors to new markets for 3D printing that need precision parts made safely and sustainably.”

Kalambi told me that the RIZE 2XC has plenty of great features, such as a heated build plate, a camera for monitoring prints, and automatic bed leveling. Because the company’s Augmented Polymer Deposition (APD) platform has not been added, the system does not print in color, but he said that it does have “a much bigger build volume” in comparison to other desktop printers.

“It’s great for home and office use, as those industries wanted a good printer within a certain price point,” Kalambi explained. “Lots of 3D printing is being done in schools and offices, which is why we partnered with Sindoh…they have lots of knowledge in the education field. That industry had a requirement for a low-cost printer, and RIZE wanted to be able to offer a more affordable option.”

Kalambi also said that the RIZE 2XC is great for 3D printing industrial parts.

According to the RIZE release, this new printer is the first that has brought “safe, sustainable 3D printing” to the industry’s compact sub-$5k market, which can help organizations struggling to get back on their feet in a post-pandemic world get a leg up over the competition.

“Sindoh’s cooperative R&D effort with RIZE showed us that we chose the right partner indeed – a partner as committed to innovation in materials and technologies as we are. We’re delighted to expand our reach into more segments of the market through the cooperative solutions we are creating with RIZE,” said BB Lee, CEO, 3D Printing Division at Sindoh Co., Ltd.

The RIZE 2XC will be available from RIZE’s network of channel partners starting June 30th, for an introductory price of $3,995 in the US market and €3,995 in Europe. In the meantime, I’ll be keeping my ear to the ground, because Kalambi said RIZE will have some more exciting news to share with us in mid-July.

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Phil Schultz of 3D Systems on 3D Printing Supply Chain Assurance

Phil Schultz is executive vice president of Operations at 3D Systems. As a seasoned 3D printing exec, he leads all on-demand operations there. Before that, he lead Foxconn’s printing business and spent 25 years at HP, ultimately leading their consumer inkjet offering. I interviewed Phil and enjoyed his measured, thoughtful responses, which showed his deep understanding of the possible and impossible of additive. 

The current crisis has exposed the brittleness of our just-in-time manufacturing world. Small ripples in the system can propagate, reinforce themselves, and cause waves that, in turn, build up to a storm, collapsing the system. A factory in Thailand closing or a freighter being diverted can wreak havoc on the intricate supply chains that connect our globalized society. A system that is so massive and world-spanning as global commerce and transport turned out to shatter easily in a difficult situation. Many global organizations are now discovering that they need to do more to audit and update their supply chains. Supply chain resilience once meant that you had more than one supplier for critical components. But now we all know that we need to look further to assure supply. What role can 3D printing play in this? 

Phil differentiates between “short-term and long-term supply chain interruptions.” “Especially in an emergency…3D printing can help” and do so much faster than other technologies can. If “additive is a contingency or it is used in bridge manufacturing,” it is often an excellent choice. We “don’t need any tooling…and we’re not bound to a geography” with 3D printing “through a distributed manufacturing model…or one order being delivered globally” we can respond in a crisis, and we’re “lightning fast.” Especially for “small parts in runs of a 100, 1,000 or 10,000…additive has the advantage.” 

The “downside with 3D printing is the materials…that your parts are different than injection molded parts,” and “part properties and strength may not be the same.” “Your parts could be good enough for the application,” but he cautions customers against entering into production “without qualification…because then you’re carrying a lot of risk.” There will also be “cost differences…and often increased costs mean that without mass customization additive may not always make sense.” 

He likes to take customers through “a simple calculation…that often shows that pricing represents “multiples of an injection-molded part—not 20% or 30% higher—multiples” and, in that case, if “you’re going to do a replacement of a conventional part,” the business case falters. In that case, “you’d only do it because you have no choice.”

However, if you “learn to design for the technology…and use it to combine parts…lose weight…bring value,” it changes the equation. “Why would you want this is part to be 3D printed…and what does that mean for your business?” He maintains that “3D printing is…not a replacement for CNC or injection molding…it is just another tool” and “you must use it wisely.” 3D printing can help you “guard against the future…and find your future more quickly,” but it is no panacea. 

A 3D Systems On Demand site in Lawrenceburg, TN.

A 3D Systems On Demand site in Lawrenceburg, TN.

There are often overlooked alternatives, made possible by 3D printing, that allow for more scale and lower costs. This includes “3D printing positive investment casting print patterns,” “using Real Wax for lost wax casting,” or “directly 3D printing low-pressure injection molds.”

“By casting urethane..or through thermoforming inserts” relatively low-cost parts can be made in the millions, as Invisalign already does with the latter technology. In “thermoforming, some customers are making over 400,000 parts a day,” through the use of 3D printing as an intermediate. Yes, in an emergency, he understands that people are printing face shields. But, if we step back, then we can consider making the headband through thermoforming or urethane casting and using an acetate screen to sterilize the parts more easily. Phil continually seeks to use additive for the right applications, the right parts. “We are geometry agnostic, require no tooling, and we are fast to the first part, but must be aware of the tradeoffs in materials and more expense.” 

3D Systems MJP Wax

He’s excited “by making spare parts out of polyamide…through sintering…especially of filled materials” and, also, “new possibilities in TPU.” Higher temperature resins for SLA are also pushing the envelope of what is possible there. Now, “we are getting resins with good flexural strength, elongation…that make parts that can bend well while being less brittle.” 

When he does introduce 3D printing for manufacturing at a firm, he likes to “start with the applications people..and walk the (production) lines…to see how we can help… We can evaluate our services…your parts…and see what sense it makes to outsource or do in-house.” Ideally, he’d like to “get into the design phase…and help companies with qualification..or share with them how to qualify products for additive.” Surprisingly, one of the sectors that he is most excited about is EMS and contract manufacturing firms.

“They have tonnes of injection molded parts…many indirect parts…and can often use additive in the short term…but have not considered it for more.” With these businesses, “almost every fixture and tool can be improved, adjusted or is now more quickly consumed,” making it more suitable for additive. “An iPhone production line may have 600 people on it and as many steps. Imagine a five percent improvement.”

He likes asking manufacturing firms, “what do you need?” and then “having complex conversations about matching material properties to needs…avoiding tooling…and the level of proof required for them to proceed.”  He’s now increasingly seeing “ducts, knobs, connections, functional parts in gear trains…and on the whole, things that are more functional in assemblies” being made with additive. A few years ago, he only used to “talk to R&D, and now we talk with [operations]…about things that I care about, such as cycle time.”

3D printing “is emerging as a backup plan….but you have to design for it… 3D printing services could, through their hundreds of machines…solve customer problems,” but firms could also have 3D print capacity in-house for the most relevant materials to them. Either way, qualified parts can be manufactured at scale, but not all parts can be made cost-effectively through 3D printing.

It is clear from Phil’s recent experience that additive is maturing and new applications are being discovered all the time. New realism is unlocking actual manufacturing and, in due time, we could provide true supply chain reassurance through 3D printing. Ultimately, “I want to go in front of every industrial engineer in the world and show them how their creativity can be unleashed with 3D printing.” 

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NASA Wants Aerojet Rocketdyne to Make More Rocket Engines with 3D-Printed Parts

On its first launch, NASA‘s uncrewed Space Launch System (SLS) mega-rocket will go on a trip around the Moon as part of the initial test flight for the Artemis 1 mission. It will mark the beginning of one of the most talked-about space programs this year, Artemis, an ongoing government-funded crewed spaceflight initiative with the goal of landing the first woman and the next man on the Moon by 2024, particularly, on the lunar south pole region. The most powerful rockets ever built, the SLS is in turn powered by four super engines that are designed to handle some of the most extreme temperatures as they move massive amounts of propellants to generate enough energy for the rocket to escape Earth’s gravity.

As part of a years-long working relationship with NASA, Aerojet Rocketdyne of Sacramento, California, will be building a total of 24 RS-25 rocket engines to support as many as six SLS flights for a total contract value of almost $3.5 billion. Originally slated to produce six new RS-25 engines, the company has recently been awarded a $1.79 billion contract modification to build 18 additional RS-25 rocket engines to support future deep space exploration missions.

“This contract allows NASA to work with Aerojet Rocketdyne to build the rocket engines needed for future missions,” said John Honeycutt, the SLS program manager at NASA’s Marshall Space Flight Center in Huntsville, Alabama. “The same reliable engines that launched more than 100 space shuttle missions have been modified to be even more powerful to launch the next astronauts who will set foot on the lunar surface during the Artemis missions.”

Although the Space Shuttle Endeavour is now at a museum exhibit at the California Science Center in Los Angeles, its engines—along with those that used to power space shuttles Discovery and Atlantis—have been maintained for SLS. However, unlike the shuttles, SLS will not reuse its engines. Once the core stage falls away at around eight minutes after launch, the engines will disintegrate during reentry. There are currently 16 RS-25 engines remaining from NASA’s Space Shuttle Program that Aerojet Rocketdyne has upgraded, tested, and that are ready to support the first four SLS missions. Yet, with more SLS missions expected to launch well into the end of the decade, Aerojet Rocketdyne has been asked to build more engines; actually, six new expendable RS-25 engines are already being assembled using advanced manufacturing techniques, including 3D printing, that reduces both the cost and time for manufacturing each engine.

The additional 18 engines will continue to leverage supply chain optimization and the incorporation of additive manufacturing (AM) techniques that were already introduced in the initial SLS engine production.

Initial SLS Configuration, powered by RS-25 rocket engines (Credits: NASA)

Employing AM technology to reduce costs and improve the efficiency of its engines is among the top priorities of the aerospace and defense company. Aerojet Rocketdyne’s senior engineer on the Additive Manufacturing team, Alan Fung, told 3DPrint.com that hundreds of people have been working on the design, development, and manufacture of the engines which relies mainly on laser powder bed fusion technology to additively manufacture at least 35 parts on each engine. 

“Our primary focus is to make reliable, robust printed parts, that will work 100 percent of the time. We started designing some of these pieces a couple of years ago to make sure they were tested and certified for NASA’s space program, which is crucial to the safety of the upcoming crewed missions,” said Fung. 

AM Team at Aerojet Rocketdyne, from left to right: Bryan Webb, Ivan Cazares, and Alan Fung (Credit: Aerojet Rocketdyne)

With the delivery of these new engines scheduled to begin in 2023, the team is not wasting any time. Fung said that “part of the big quest in the first round was to work with NASA closely on developing the certification processes.” Revealing that “we now have a process to make parts using AM that we know is safe and it is exactly what we need to make sure that our parts will work on the engines that will power future SLS missions.”

3D printing simplifies the production of several RS-25 parts and components, making the engine more affordable to produce while increasing reliability. With fewer part welds, the structural integrity of the engine increases. This is a very manual, complex manufacturing process. In fact, rocket engines are so complicated to build, that only a handful of countries have been able to manufacture them.

“That’s where AM really shined for us. We were able to get rid of many welding joints and just incorporate the processes automatically, getting down the part count and reducing the load across the engine,” said Fung.

One of the largest 3D-printed components of the engine was the critical “Pogo” accumulator assembly. Roughly the size of a beach ball, the complex piece of hardware acts as a shock absorber to reduce oscillations caused by propellants as they flow between the vehicle and the engine. Fung described the 3D-printed component as a critical part of the engine because it helps smooth the ride for astronauts and the vehicle ensuring a safe flight. Moreover, he explained that the Pogo used to demand more than 100 weld joints that had to be done manually and took almost four years to make, while the 3D-printed Pogo developed at Aerojet Rocketdyne’s factory in Los Angeles, brought the welds down to just three, and was finished in less than a year.

Some of these modified components have already been tested during engine tests that replicate the conditions of flight. For example, during a 400-second test at NASA’s Stennis Space Center, Aerojet Rocketdyne was able to successfully evaluate the performance of the 3D printed Pogo accumulator assembly.

“We expect that more and more engines will be additively manufactured in the future, leaving behind a lot of traditional rocket engine manufacturing processes that are very difficult, and allowing us to print more engines. Eventually, the time to build is going to go down even more, especially as the industry gears towards incorporating more lasers and bigger machines; which is good for us, because our engines keep getting a little bit bigger than the last ones. So, when those machines get to be bigger, use more lasers, and print parts faster, then that’s when we will see a really big shift in the way we make rocket engines,” went on Fung. 

Artemis I RS-25 Engines (Credits: Aerojet Rocketdyne)

Working with NASA, Aerojet has implemented a plan to reduce the cost of the engines by more than 30% on future production when compared to the versions that flew on the Space Shuttle, all thanks to more advanced manufacturing techniques, like AM, that help the engineers modify some of the rocket components.

During the flight, the four engines will provide the SLS with around two million pounds of thrust to send the heavy-lift rocket to space. The rocket engines are mounted at the base of a 212-foot-tall core stage, which holds more than 700,000 gallons of propellant and provides the flight computers that control the rocket’s flight.

The AM team at Aerojet is using GE Concept Laser and EOS machines for its selective laser melting requirements. Fung said they were using superalloys, mostly nickel-based for the engine parts being 3D printed, due to its outstanding corrosion resistance, high strength, and ability to resist hydrogen embrittlement due to the hydrogen fuels found in most of Aerojet Rocketdyne’s liquid propellant rocket engines.

“These new RS-25 engines are an upgrade from the Space Shuttle engines, which were already some of the most reliable engines made in history. Engineers spent 40 years making the shuttle engines as reliable, safe and high performance as possible; but with additive manufacturing we thought we could also try to get the cost down. This technology will revolutionize the way we build engines” 

With so many challenges ahead, having certified rocket engines to take the next lunar explorers to orbit feels like a stepping stone for the journey that lies ahead. After all, the SLS rocket is part of NASA’s backbone for deep space exploration and will prepare humans for long-duration space travel and the eventual journey to Mars.

Space Launch System (SLS) (Credits: NASA)

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Marine Biologist Modifies Bioprinting for the Creation of Bionic Coral

Corals are dying globally. In the face of climate change and global warming, we can expect some severe consequences, which in turn directly affects marine life. In what is panning out to be a mass extinction event, coral reefs have been dangerously threatened by toxic substances and excess carbon dioxide for years, causing the certain death of may of these diverse marine invertebrates. Once the coral is dead, the reefs will also die and erode, destroying important marine life, that would otherwise feed and spawn on it.

Considering that scientists have predicted that nearly all coral reefs will disappear in 20 years, it is crucial that we protect corals and learn from them. For the expanding field of biotechnology, untapped resources like corals hold great potential, as bioactive compounds for cancer research or simply as an inspiration for the production of bioenergy and bioproducts.

In an interview with 3DPrint.com, interdisciplinary marine biologist Daniel Wangpraseurt, from the University of California San Diego (UCSD)’s Department of NanoEngineering, explained how bioprinting technology was a pivotal point in his work to develop bionic 3D printed corals as a new tool for coral-inspired biomaterials that can be used in algal biotechnology, coral reef conservation and in coral-algal symbiosis research. 

“For many years I have been studying how corals optimize light management and discovered that there are lots of interesting evolutionary tricks, such as different growth forms and material properties, so I became interested in copying these strategies and developing artificial materials that could host living microalgae, just like corals do in nature,” revealed Wangpraseurt.

Daniel Wangpraseurt

As one of the most productive ecosystems globally, coral reefs use photosynthesis to convert carbon dioxide into energy that they in turn use for food. Even though light provides the energy that fuels reef productivity, key nutrients such as nitrogen and phosphorus are also required, but are found in very low quantities in warm tropical oceans where coral reefs are generally found, making scientists wonder how these marine animals have managed to create a competitive habitat with such limited resources.

A laser beam is intensely scattered by elastic coral tissue and aragonite skeleton. (Credit: Daniel Wangpraseurt)

Wangpraseurt described that, while different corals have developed a plethora of geometries to achieve such capabilities, they are all characterized by an animal tissue-hosting microalgae, built upon a calcium carbonate skeleton that serves as mechanical support and as a scattering medium to optimize light delivery toward otherwise shaded algal-containing tissues.

“Taking what we learned about corals and biomaterials, we began working on a project to develop a synthetic, symbiotic system using a 3D bioprinting approach. We know corals have both animal cells and algal cells, and, so far, we have mimicked the animal part of the corals, that is, the physical and chemical microhabitat that partially controls the activity of the algal cells.”

At UCSD, Wangpraseurt expects to continue recreating coral-inspired photosynthetic biomaterial structures using a new bioprinting technique and a customized 3D bioprinter capable of mimicking functional and structural traits of the coral-algal symbiosis. Along with fellow researchers from UCSD, the University of Cambridge, the University of Copenhagen and the University of Technology Sydney, and thanks to a grant from the European Union’s Horizon 2020 research and innovation program, and the National Institutes of Health (NIH), the team reported the results of their work on bioinspired materials that was published in the journal Nature Communications earlier this year.

“We want to go further and not just develop similar physical microhabitat but also modulate cellular interactions, by mimicking biochemical pathways of symbiosis. We hope that this allows us to not only optimize photosynthesis and cell growth, but also to gain a deeper understanding of how the symbiosis works in nature. By doing so, we can improve our understanding of stress phenomena such as coral bleaching, which is largely responsible for global coral death.”

Living colonies of Symbiodinium are visible within the 3D bioprinted tissues (Credit: Daniel Wangpraseurt)

So, how did bioprinters become the go-to technology for this project? Wangpraseurt explains that, while working as a researcher at the University of Cambridge’s Department of Chemistry Bio-Inspired Photonics lab, he noticed that scientists were using cellulose as a biomaterial with interesting optical responses. He was wondering how he could use cellulose to develop a material with very defined architectural complexity. 

“In the beginning, the main aim was to develop a coral-inspired biomaterial, that has a similar optical response as natural coral, and then to grow algae on it or within it. Thereby, we started off with simple techniques, using conventional 3D printers; however, it wasn’t very easy to recreate the spatial resolution we needed for corals.”

Inspired by 3D bioprinting research in the medical sciences, Wangpraseurt reached out to scientists at the UCSD NanoEngineering lab that were developing artificial liver models, and who later became collaborators in the project.

A laser beam is intensely scattered by elastic coral tissue and aragonite skeleton (Credit: Daniel Wangpraseurt)

The team went on to develop a 3D printing platform that mimics morphological features of living coral tissue and the underlying skeleton with micron resolution, including their optical and mechanical properties. It uses a two-step continuous light projection-based approach for multilayer 3D bioprinting and the artificial coral tissue constructs are fabricated with a novel bioink solution, in which the symbiotic microalgae are mixed with a photopolymerizable gelatin-methacrylate (GelMA) hydrogel and cellulose-derived nanocrystals (CNC). Similarly, the artificial skeleton is 3D printed with a polyethylene glycol diacrylate-based polymer (PEGDA).

Close up of coral polyps and living photosynthetic biomaterials. Living colonies of Symbiodinium are visible within the 3D bioprinted tissues (Credit: Daniel Wangpraseurt)

Based in San Diego, Wangpraseurt has spent months trying to recreate the intricate structure of the corals with a distinguished symbiotic system that is known to grow as it creates one of the largest ecosystems on the planet. 

“We used a 3D bioprinter that had been developed for medical purposes, which we modulated and further developed a specific bioink for corals. A lot of the work was related to the optimization of the material properties to ensure cell viability. Having the right bioink for our algal strains was crucial as if we were to use mixtures commonly used for human cell cultures, the cells will not grow very well and can die rapidly.”

The implications of the newly developed 3D printed bionic corals capable of growing microalgae are many. Wangpraseurt said he plans to continue working on bionic corals and potentially scale up the process for his startup, called mantaz, as well as for commercial properties; or to develop coral-inspired materials at a larger scale to have a more immediate impact on efforts related to coral reef restoration, and also for biotechnology.

SEM images of the skeleton structure of the coral Stylophora pistillata and the coral-inspired, 3D-printed material (Credit: Daniel Wangpraseurt)

Wangpraseurt is looking to scale the bioprinting system to have a more immediate impact on algae biotechnology, bioenergy, and bioproducts. He claims that he and his colleagues can “customize the environment of the algae and fine-tune the production of a certain bioproduct to potentially tap into the algae bioproduct market and scale the system for bioenergy production.” 

“Another interest of mine is to further develop a 3D bioprinted synthetic coral-algal symbiosis system, which can provide important insight into the mechanisms that lead to coral death, but can also result in the development of future technology for coral reef restoration.”

The researcher talks about coral reefs with a reverent passion that today goes beyond his lab work. When he is not moving the research along at USCD, Wangpraseurt is working with his social enterprise in Panama, as he and his team try to restore coral reef ecosystems to help coastal communities in the tropics, including local fishermen, by harvesting algae biomass that can be sold for different purposes, such as natural fertilizer, which contributes to an organic and sustainable chain of production. Furthermore, the coral-inspired aspects of Wangpraseurt’s research and startup company are really coalescing to enable him and his team to understand how corals work and, in turn, how we can learn from them for the benefit of our planet.

Nutrient sampling at a polluted reef in Panama (Image: Daniel Wangpraseurt)

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The Full-Color Voxel Woman: 3D Printing the Complexity of Human Anatomy

Creating anatomical 3D models with cutting edge technology can forever change the way anatomy and medicine are illustrated. At Victoria University of Wellington (Victoria), in New Zealand, students are quickly learning new ways to give life to clinical data. Moving data from the 2D world to a tangible, highly detailed, and precise 3D printed anatomical model could significantly change the clinical field; revamping everything, from medical education to clinical practice.

Focused on bringing her creative designs to life, Ana Morris, a post-graduate student at the School of Design Innovation at Victoria, managed to 3D print a full-color, anatomically accurate, and high fidelity voxel human using the Visible Female dataset and a bitmap-based additive manufacturing workflow.

The result of the work, part of Morris’ master’s thesis, is visually astounding and the woman replicated within this new kind of anatomical model is almost palpable. It was created using serially sectioned cryosection images of a female cadaver produced by researchers working on the National Library of Medicine’s Visible Human Project (VHP).

Ana Morris (Credit: Victoria University of Wellington)

Using a Stratasys J750 3D printer, Morris was able to replicate in an entirely novel way the body of a woman who, as a result of morbid obesity, died of heart disease. Victoria’s School of Design Innovation has been working with Stratasys printers since 2004, and this J750 machine used to create lifelike anatomical models with standard or complex pathologies for device testing, surgical training, and patient-specific simulation, provides the color, flexibility, and transparency in 14-micron droplets.

The VHP project realized as a full-color exploratory model (Credit: Ana Morris/Victoria University of Wellington)

Working alongside lecturers Bernard Guy and Ross Stevens of the School of Design Innovation, Morris was granted free access to use the sophisticated Stratasys machine. Just like all her classmates, she was encouraged to “learn at the edge” and “exploit her creative thinking,” as Guy described during an interview with 3DPrint.com.

“This particular piece is a component of a larger project by Ana [Morris] that works with data that doctors use all the time – like MRI and CT scans. It provides an example of how industrial designers at Victoria take data and convert it into a physical object, and also how to advance scientific thinking, serving as a catalyst that can transform research,” said Guy.

“We have the advantage of talking to anesthesiologists and surgeons all the time, who have recently suggested that this voxel human piece would be a fantastic exemplar as a visual aid for patients, to show them what’s inside the body and what can happen during a procedure, without being scary or too scientific.”

The full data set from the VHP is now publicly available, allowing Morris the opportunity to volumetrically reconstruct the dataset in a new way.  Originally conducted in the 1990s by the University of Colorado Health Sciences Center to obtain serially sectioned images of human cadavers for medical research advancements, the VHP became a common reference point for the study of human anatomy

Anatomical medical modeling using traditional mesh-based workflows can be time-consuming. Data loss and segmentation artifacts, due to multiple post-processing steps, can cause anatomically inaccurate 3D prints. Morris stated that, when using current segmentation workflows, each mesh (STL file) is restricted to one color and density. However, her study takes advantage of a high-resolution multi-material 3D printer that allows for control over every material droplet (also referred to as a “voxel”).

Guy and Stevens believe that “3D printing with voxels is a little bit like looking at tiny dust particles in the sun; it’s that sort of detail that we are working with, tiny little particles. Our big question is now, what do people want to see in a physical object with this level of detail? We don’t want to keep printing more superfluous products”.

The natomically accurate 3D printed model of the Visible Female, a woman who died of heart disease caused by obesity (Credit: Ana Morris/Victoria University of Wellington)

“There are plenty of virtual reconstructions, but I don’t think the human anatomy has ever been printed like this before,” Morris suggested to 3DPrint.com. “Moreover, a model like this highlights the potential of what could come next and will hopefully spark ideas of what could be done. For example, the model could serve as a visual communication tool used in a setting between a doctor and patient, removing all the clinical jargon, helping patients have a more comprehensive understanding of the human body.”

Morris’s workflow can bypass the conversion steps of traditional segmentation workflows, resulting in the preservation of cadaveric anatomy in its true color. Furthermore, because of the time saved using a bitmap-based 3D printing approach, Morris’ workflow has the potential to save money when compared to traditional medical modeling workflows. The highly accurate model was produced with gradated color including details at 14-micron resolution which, according to Morris, is impossible to achieve using STL file formats.

The four-step process starts with data acquisition. In this case, the Visible Female dataset, which is then volumetrically reconstructed to create a virtual model. From here, the data is scaled-down and resliced at the printer’s native printer z resolution. It is finally 3D printed and post-processed.

The detail that can be seen in the 3D printed Visible Female shown in this research is unprecedented. A total of 5,102 images were processed and sent for printing on the Stratasys J750 to complete the Visible Female 3D print, resulting in 24 individual 3D prints stacked on top of each other to form the full 3D printed Visible Female. 

Morris claimed that all the print parts vary in slice thickness, as they wanted to show that bitmap-based printing can produce both thin slices and thick blocks. For demonstration purposes, thick blocks were used to show more detailed areas of anatomy such as the hand and chest regions, and thinner slices were used to show detail through areas such as the thigh.

Model of the Visible Female (Credit: Ana Morris/Victoria University of Wellington)

Guy recalls that unlike anything previously seen in 3D printed anatomical models, this project shows the body of a person in extreme detail. “With 3D printing, we see a lot of stereotypical body forms; while here, we are witnessing a person who has grown up, lived their life, and passed away, so it is a very real cadaver, almost as a synthetic cadaver, or synthetic mummification. It shows a very real shape and form, and that’s the part of the study we wanted to focus on.” 

Morris described that when images are deposited sequentially on top of each other using the Stratasys J750 3D printer, it can construct a tangible 3D model. Inspired by Massachusetts Institute of Technology (MIT) research where a bitmap-based 3D printing workflow allows the ability to engineer different material combinations at a 14-micron resolution by fusing different material droplets.  Advantages recorded around bitmap-based 3D printing have acknowledged that in its strength lies its accuracy, limitless manufacturing possibilities, and the production of complex material combinations at a microscale.

“Students at Victoria are aiming to mimic anatomy using synthetic materials,” described Guy. This is part of their ability to craft and shape voxels with medical data. The challenge that many professors and students at the School of Design Innovation are undertaking is to show another level of detail, gradients, density, color, and heterogeneous material combinations to fulfill growing demand from the medical field.

“We are at a time when healthcare professionals are not sure what is achievable, but they also don’t know what question to ask and our job is to show them what we can do,” suggested Guy.

For Morris, the aim of this project was to explore the bitmap-based 3D printing technique and the capabilities of the Stratasys J750 3D printer. “After this, we could expand into densities and biomechanics, which are more complicated areas,” she said.

According to Morris, “having control over every 14-micron material droplet means that materials can be engineered to produce models with varying colors and densities,” and even more interesting is how this “manufacturing workflow could be used for a variety of different medical applications where bioimaging datasets are needed to create tangible anatomical models.” 

Finding a balance between science, creativity, and art is one of Morris’s strong points and what led her to carry out this endeavor, something she described as a way to “humanize and democratize information about our anatomy and clinical vocabulary through design.” Indeed, her bitmap-based additive manufacturing model has helped to show the Visible Female in an unprecedented way. 

Display of sections of the Visible Human (Credit: Ana Morris/Victoria University of Wellington)

After presenting this research at the 3D Technologies in Medicine 2019 Conference in Melbourne last year, Morris and Guy expect that future research will involve looking at medical datasets to print models that are soft and hard altogether. They expect to work on the complexity of 3D color and movement to display the dynamics of the body using the sophisticated and new Stratasys 750 Digital Anatomy Printer (DAP).

“Anatomical models today are a weird snapshot in time, so I want models that mimic the complexity of a body in movement, such as tissue movement in breathing. The desire is to get as close as we can to anatomy, by mimicking the reaction of the different parts of the body when it moves, as opposed to static anatomical models that are falsely imitating reality,” explained Guy. “And now thanks to Ana’s method, we can move forward, knowing that if we are really sharp, we can make a difference.”

Full-color serially sectioned images of the Visible Female (Credit: Ana Morris/Victoria University of Wellington)

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Interview with Roscher Van Tonder on Simplified Manufacturing with Additive Manufacturing

Roscher Van Tonder

Managing Director and Founder of AMTC, Roscher Van Tonder takes us through an interesting topic on Simplified Manufacturing in 3D Printing and Additive Manufacturing. Currently based and operating in South Africa, Roscher is actively involved in the sector through consulting and printing as a service.

What is it that you do? 

The manufacturing world is changing and it is daunting to many companies out there, the rise of I4.0 has a lot of people unsure of what the correct direction is for the business relating to AM.

AMTC Pty Ltd goal is to supply a unique set of systems, strategies, additive manufacturing equipment, and materials to our customers and to cater for a wide range of industries ranging from, Aerospace, Automotive, Manufacturing industry, Mining, Oil & Gas, Metal Casting to the Defence industries.

Our scope is to assist companies to adopt AM by creating successful business cases with exceptional ROI. These business cases complement the current business workflow. We look at the business as a whole and we identify the core areas where the maximum benefit will be reached by implementing AM for sustainable successes.

AM-WorX addresses all the business areas to ensure total coverage and ensures maximum benefit to the bottom line.

The main stages of AM-WorX

  • An onsite audit (Gauge potential AMT scope)
  • Business readiness analyst (Current and lacking AM Experience/Gaps/Skills )
  • Market review ( current and potential new markets and opportunities)
  • Parts/Product review (Ascertain the printability of the product/parts)
  • Develop the new processes and skill framework for AMT integration

By aligning with some of the bleeding edge technology companies out there the result is a business case that shows a minimum potential revenue increase compared to current company revenue over the planning horizon by showing the 10x Value guarantee by unlockable the value of AMT in the business.

Can you also explain the Simplified Manufacturing line of thought concerning 3D printing and Additive Manufacturing?

Our slogan “simplified manufacturing” comes from the benefits that technology brings to the table.

Time Reduction of the new product to market.

Additive Manufacturing has been seen as an R&D tool, the last 2 years the change to the final product has taken shape. The company that gets the product out into the market the fastest has the leverage, the technology typically cuts these times by 40-60%.

Customization & Mass customization

The instant gratification culture created by online stores and the internet is spilling over to the manufacturing industry. The ability of a company to leverage mass customization will give them an advantage on their competition, Additive manufacturing is allowing companies to move away from minimum batch volumes and give the freedom to offer customized products on-demand as per customer preference in a short amount of time.

 

Various Products and models from Prototyping to Mass Customization

On Demand Manufacturing

One of the biggest benefits of Additive Manufacturing is that it enables on-demand manufacturing. The ability to manufacture parts at the point of need points to a shift from “make-to-stock” to a more sustainable “make-to-order” model for low-volume production of spare parts.

Lead Time reduction

Hydroforming is primarily used for low volume forming of sheet metal parts while thermoforming is mainly used for high volume forming of plastic sheets. The tooling used in these processes is typically produced by CNC machining of materials such as aluminum or wood which typically involves high costs and long lead times. Additive manufacturing makes it possible to substantially reduce the cost and lead time involved in making these tools while offering additional design freedom and reducing tooling weight.

Simplified Manufacturing process

Part consolidation

AM is uniquely capable of producing complex geometries that can’t be manufactured using legacy manufacturing. A mechanical assembly that would normally have many parts fabricated as separate components and then assembled can be additively manufactured as a single unit, even if the geometry is very complex. In addition to design simplification, there are other tangible benefits to using AM for part consolidation. This leads to lower overall project costs, less material, lower overall risk, better performance.

Tool-less manufacturing

We give users the ability to deliver end-use parts directly from CAD files, saving cost by cutting out tooling requirements. Benefits: Accuracy and repeatable production, High-speed printing production, Material flexibility, and versatility, improved time-to-market and part mass-customization, Low Total Cost of Operation (TCO) and low per part cost & scalable options to meet growing needs.

Manufacturing Process step reduction

The technology can reduce current legacy manufacturing processes by up to 70%. Cost-saving implications are extensive as well as risk reduction and resource savings to the company. For exaample, in an investment cast application AM can reduce the production steps from 7 steps to 3 steps.

What impact can Simplified manufacturing with 3D Printing have, especially on African economies?

We believe that Africa is sitting on an opportunity that could change the Africa continent forever. AM technology brings the ability for SMEs to not just compete but to lead supply of manufactured parts, become self-sufficient, by exporting final products that are created from our raw materials, creating sustainable economies throughout Africa. The danger is if we miss this opportunity Africa will probably never become a major player in the manufacturing world. Why should we be following if we can lead?

Are companies especially in supply chain ready or prepared for 3D printing?

The process of manufacturing, storing, and delivering spare parts is a time-consuming and laborious one for OEM, s and remote operations. Costly warehouse, transport & logistics, storage of spare parts in addition to time-intensive lead times and shipping are just some of the difficulties faced. I believe that some Multi-national companies are getting ready, however in South Africa only a handful are starting to look at AM. As Africans, we are very slow to change and adapt to “New” we don’t like change and have a mentality of “if it’s not broken why fix it” and this is hindering the widespread adoption of AM.

The change and adoption must come with a clear vision from top management that drives the vision, this is a new way of doing things potential changing the whole business model and logistics will be one of the hardest hits I believe. Savings of 30-60% on stock holding can be achieved with AM.

 

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Keith Murphy: “We Believe We are Discovering the Next Step in Drug Development”

It’s been three years since Keith Murphy and Jeffrey Miner joined forces to create the biotechnology company Viscient Biosciences. In 2017, the co-founders had recently left their previous successful enterprises and were looking to continue working in the field of biotech and pharma, seeking to contribute their know-how to drug discovery. Thanks to their expertise, innovative strategy, and vision, they began tackling a big industry by tentatively trying something different: using bioprinted tissue instead of animals to model disease for drug research and discovery.

During an interview with 3DPrint.com Murphy discussed the potential success of the company’s developments as well as everything that he hopes to accomplish for the future. At Viscient, founding partners Miner and Murphy became interested in driving drug discovery in a previously unavailable context. Viscient’s CEO, Murphy was also co-founder of pioneer bioprinting firm Organovo and was its CEO and Chairman from 2007 until 2017.

After Murphy left Organovo, he began working with Miner, who had just left Ardea Biosciences after a successful buyout by Astra Zeneca for 1.2 billion dollars. During that time, the co-founders were interested in the potential capabilities of using bioprinted models instead of animal ones to predict disease. The core idea for Viscient was to develop tissue that would better represent the native environment for human biology in a way that researchers could use for drug discovery. Murphy considered that the traditional reliance on animal models of disease today often leads to clinical trial failures due to species differences that prevent accurately reproducing human disease. Further inquiry into the specifics of why clinical trials fail where animal models didn’t lead him to understand that they needed to focus on a human-friendly approach.

“For a long time, animal models have been very productive because there are a lot of things that are similar between animals and humans and researchers did a great job of finding those areas that could help us learn,” said Murphy. “Yet, what drives the failures in clinical trial settings is often the difference between animals and humans. Not everything that works in animals works on humans.”

That is why San Diego-based Viscient is working at the intersection of human 3D tissue technology and multi-omics (that is genomics, transcriptomics, metabolomics) analysis to discover and develop drugs across a range of therapeutic areas with a significant unmet medical need, leaving behind animal models.

Miner and Murphy put together a team of scientists that had worked for Ardea during the discovery of the company’s main drug candidate, lesinurad, for the treatment of gout and hyperuricemia, as well as a research contract with Organovo to use its bioprinting tech, they moved forward with their plan. Since then, Viscient has built up the capacity to carry out the research themselves, as well as developing their own internal biprinting and other 3D biology capabilities to the point where they have a fully capable platform for discovery and development of drugs.

Viscient has progressively moved forward using 3D liver tissue to discover drug opportunities for very persistent and expanding fatty liver diseases called non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). 

“During the last two years, we have been working with NASH, taking the disease out of a patient’s body, and showing that we can accurately reproduce it. As the next step, we used tools to look at what genes are turned on and off in a bioprinted healthy tissue versus a diseased one. So that at this stage we know which genes are turned on, those are all potential targets that could help us eventually develop a drug.

“The next step after that was to make tissues and attempt to knock those target genes down, and by doing that we have identified a set of validated novel drug targets for fatty liver disease. When we block the gene that is causing the disease, we see the fibrosis go down in the 3D model, which means we have found a way to potentially treat that disease, and the next step is to find a drug that can block the effects of that gene in a patient.”

Bioprinter (Credit: Viscient Biosciences)

Indeed, today Viscient is looking at things such as fatty liver disease. Murphy considered that the results have been consistent with the expectation since their findings using bioprinted tissue are naturally different from the animal models, which is why nobody else is finding them. He claims that this particular disease “is a classic case where animal models are not working, and there have been probably close to 20 drugs go into human trials that have not worked but had previously been successful in animals.”

Viscient’s bioprinted NASH model imitates the disease in humans very accurately. In fact, Viscient’s model matches the liver biopsy from a patient with fatty liver disease NASH. In NASH, the fat that builds up in the liver and collagen is a marker of fibrosis, so the bioprinted tissue actually reflects the fatty droplets and collagen fibers seen in the patient tissue biopsy. Under the microscope, the two tissues look very similar, and hard to distinguish them for the untrained eye.

Biopsy from a patient with NASH (Credit: Viscient Biosciences)

We think we are discovering the next step in drug development. These new 3D cell cultures can be more predictive than animal models. It’s still going to take some time to develop our own drug, but we can speed things up by partnering with established pharma companies. And considering that we have multiple targets, we can run multiple programs. At this stage, there is a big funnel with a broad range of targets that could work or not,” revealed Murphy. “However, I think that our success rates are going to be higher than traditional methods once we get into the clinical phase, but that doesn’t mean that there might be a few surprises on the way that could delay our plans.”

Murphy recently revealed that Viscient will turn its attention to 3D bioprinting lung tissue for infectivity research to assist global efforts to combat SARS-CoV-2, the novel coronavirus that causes COVID-19.

“What we know broadly speaking, is that infectivity – that is, the ability for a virus to get inside a tissue – is higher using 3D models. We haven’t worked extensively with lung cells yet, but we believe that we can make a really compelling model very quickly,” Murphy asserted. “We feel that we have this ability to model bioprinted tissue and that is what the Coronavirus response calls for. Furthermore, we wish to contribute to the global efforts with a model that we believe will help with the selection of the best therapeutics.” 

Thanks to their bioprinted tissue models, Viscient expects to identify which patients benefit from each kind of drug being tested against COVID-19. Since drugs like chloroquine, hydroxychloroquine, the antiviral medication remdesivir, or the antiviral combination of lopinavir and ritonavir are all generic, Viscient can start working with academic and non-profit partners.

“There are researchers worldwide working on vaccines, and we can potentially help make sure that they are correctly getting inside the tissue, and training the immune system the right way,” he went on. “We are working fast, but it takes some time to build these models, somewhere between four and six months. For now, our biggest challenge is the testing turn-around time.” 

Researchers working at the lab (Credit: Viscient Biosciences)

In spite of the current situation that has hundreds of countries and companies under lockdown, Viscient researchers are continuing work under safe operating conditions. For now, Murphy and Miner are restarting lab operations to work on their lung tissue program and will soon continue focusing their efforts on NASH, but they have a lot more ideas for the future and one thing is for sure, they expect to continue working with bioprinted tissue. 

The post Keith Murphy: “We Believe We are Discovering the Next Step in Drug Development” appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

CELLINK in France: Expanding Their Portfolio in 2020

Seeking to strengthen their presence in Europe, 3D bioprinter provider and pioneer bioink company CELLINK, opened their new offices in Lyon, France, last October. Begining new partnerships and collaborations with universities, hospitals, pharmaceutical companies and more, is a big part of the core mission of CELLINK, as they combine their technology with research innovation everywhere. The city of Lyon offers a booming scene for bioprinting, with companies heavily focusing on microtumors and taking advantage of an established network that has collected more than 2000 tumors from patients in collaboration with 11 major cancer hospitals in the country via the IMODI initiative–a French consortium to develop new experimental models of cancer–which preserves and archives all tissue and cell samples developed by the consortium partners during the project.

3DPrint.com spoke to CELLINK’s Sales Director for France and Southern Europe, Edouard Zorn, who envisions a greater expansion this year, new partnerships and research collaborations: “We hope to really expand our portfolio this year in France.”

Cellink is amazing at building bridges between a product and researchers from different backgrounds and cultures. The company has a team-oriented mindset, looking to work with people from different nationalities,” sad Zorn, a biotechnology engineer with vast experience in scientific sales management.

Zorn and his five-people work team at the Lyon offices have their agenda full, with 30 customers in France, bioprinter installations, and training sessions for new CELLINK users, Zorn can’t help but highlight how fast the field of bioprinting is moving in Europe. “There are many researchers focusing on skin and cancer, that’s really big here, but lately I have also been in contact with companies working on biopharma, vaccines and some even trying to replace animal testing assays,” he stated. 

Since January 2018, CELLINK has been working with another major player in Lyon, CTI Biotech, using bioprinting to develop microtumors. CTI Biotech uses CELLINK technology exclusively for their work and now have three bioprinters at their lab, which is also located in Lyon. CELLINK and CTI Biotech had even signed a deal to 3D print customized cancer cells, with CELLINK assisting CTI in the production of patient-specific cancer tumor replicas, which will be 3D printed by combining CTI’s bioink with a sample of patients’ own cancer cells, promising to deliver personalized treatments for cancer on a custom, patient-by-patient basis.

“The aim of our collaboration is to give researchers an advantage in treating specific cancer types, and in the long term, take a serious step forward in the fight to cure cancer. CTI is moving really fast to develop models and commercialize them, and they choose our machines for their versatility, intuitiveness, and easily modifiable parameters. CTI Biotech is one of the customers we most grow with, and I believe it was a very good decision for both companies to work together,” explained Zorn. 

So far, they have already commercialized CELLINK skin for drug and cosmetic testing, which they have also been working to improve, and Zorn thinks that soon they will be working on introducing some human cells to the skin, as well as perhaps vascularizing the tissue.

Edouard Zorn (far right) and CELLINK bioprinters at the CTI Biotech labs (Credit: CELLINK)

The CELLINK office in Lyon is selling their machines to central Europe, working along the french-speaking part of Switzerland and Belgium, as well as in Spanish and Portuguese markets. 

Edouard Zorn at CELLINK France (Credit: CELLINK)

“We work with a lot of universities in France. For example, at the Medicine University of Montpellier, Xavier Garric, uses the INKREDIBLE+ bioprinter to teach master students how to design and print implantable medical devices and scaffolds for tissue engineering; and Alexandra Fuchs from the Hôpital St Louis employs a BIO X for tissue engineering.”

At the University of Grenoble, Vincent Haguet is generating skin, cornea and pancreas organoids for the modeling of organogenesis (organ formation) and pathogenesis (disease development), with a BIO X. Among these applications, organoids are used to screen and test new drugs. Also wielding the power of the BIO X is Anthony Treizèbre, from the University of Lille, for the bioprinting of Tumor-On-Chip and Blood-Vessels-on-Chip for the development of multicellular microfluidic biomimicry-based devices for the study of metastasis. Their idea is to reproduce blood vessels using human umbilical vein endothelial cells (HUVEC) and modulating the surrounding extracellular matrix.

The University of Nantes‘ Pierre Weiss also works with BIO X to print calcium phosphate-based personalized medical devices for maxillo-facial bone regeneration, as well as enzyme-based hydrogel formulation for the complex systems in bone regeneration.

Zorn believes that “there is a big demand from patients that expect the medical and bioengineering field to adapt treatments to patients. There is a lot of expectation for personalized medicine, especially with regard to microtumors for drug testing. Moreover, lately, we have seen researchers focusing heavily on immunotherapy, so I see a great future in that regard and consider that CTI Biotech is trying to position itself in that field.”

Fortunately, he suggests that there is collaboration in Europe. The European Union (EU) is financing joint collaboration projects with the objective to develop medical devices and applications with therapeutic solutions, and CELLINK wants to be a part of that.  Zorn emphasized the importance of the Silk Fusion Project, which unites scientists in the development of a technology that uses silk, a natural biocompatible and sustainable material, to produce a bioink and 3D print platelet production instrumentation, attempting to solve the limited supply of human platelets. Other projects which have CELLINK as a collaborator seek to solve problems for joint articulation, bone, and even bioprinting parts of the tendon and cartilage.

“We need people who understand cell biology, chemistry, hardware, electronics, and software, as well as a good comprehension and understanding the needs inherent to each country’s culture, that is the way in which we expand,” concluded Zorn.

Edouard Zorn at the new CELLINK offices in France (Credit: CELLINK)

The French branch of the company joins the other six worldwide offices of CELLINK, in Boston, Gothenburg, Freiburg, Blacksburg, Kyoto, and Stuttgart. Zorn hopes that the sales force along with the experienced network of professionals around the world working for CELLINK will result in a stronger presence of the company in central Europe as well as more joint efforts that could bring the future of bioprinting technology closer to our present.

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