bioprinted tissue Archives - Perfect 3D Printing Filament

Global crises can accelerate technology. Disrupting traditional responses with innovation can result in untapped opportunities that become crucial tools for humanity. This year, the Coronavirus pandemic could accelerate the evolution of drug and vaccine testing, as researchers are harnessing new technology to facilitate safety testing in people soon after preclinical work is completed on more than 60 emerging vaccine candidates. In the meantime, a bioengineering startup from South Korea could change the framework behind vaccine testing as we know it.

Founded in 2017, CLECELL has focused on the research and development of artificial tissue and has gone on to create a respiratory epithelium model earlier this year using its proprietary 3D bioprinter, the U-FAB, as well as other bioprinting technology. What is so interesting about this model is that it is expected to become a testbed for the severe acute respiratory syndrome coronavirus (SARS-Cov-2), as well as for research on the mechanisms of various other viruses.

According to a company statement, this is especially important since SARS-Cov-2 is markedly less infectious towards animals, so this new method is being considered as a potential alternative to more traditional ones that require the use of fertilized eggs to create vaccines. For more than 70 years, egg-based vaccine manufacturing has been used to make both inactivated (killed) vaccine (usually called the flu shot) and live attenuated (weakened) vaccine. Scientists would inject a fertilized egg with the virus, incubating it, and then extracting, diluting, and refining it into an antigen. Instead, CLECELL’s innovative bioprinting technique has the potential to become a testbed for various viruses.

Respiratory epithelium is a type of tissue found lining most of the respiratory tract, the role of this unique type of epithelium is to function as a barrier to pathogens and foreign particles; however, it also operates by preventing infection and tissue injury via the use of the mucociliary elevator.

The respiratory epithelium (Credit: Blausen.com staff, Medical gallery of Blausen Medical 2014, WikiJournal of Medicine)

In fact, the company’s respiratory epithelium model for in vitro testing was saught out by a team of researchers at Harvard University’s Medical School. CLECELL claims that on April 10, they received a formal letter of correspondence from Choi-Fong Cho, an assistant professor of neurosurgery at Harvard Medical School and instructor at Brigham and Women’s Hospital. The message centered around an urgent request for information on the respiratory epithelium model created with bioprinting technology.

According to the company, Cho, who is an expert in neurovascular research, the development of new drugs and neurovascular organoids, along with her research team are interested in methods to create a respiratory epithelium model through 3D bioprinting and has supposedly expressed that CLECELL’s solution will be of great assistance in conquering SARS-Cov-2.

CLECELL also suggests that Cho has professed a desire to research SARS-Cov-2’s effect on vascular structure, the virus’s infection routes, and creating an in vitro testing platform that mimics human lung tissue via CLECELL’s bioprinting solution.

Up until now, the high number of casualties from the COVID-19 pandemic has spiraled a frenetic interest in a cure, skyrocketing a profound interest from governments, research institutes, companies, and societies in drug and vaccine development, disease control, and all branches of healthcare. As a result, experts are seeking alternate methods of research that could bypass the limitations of contemporary and traditional methods for the creation of vaccines, that could take months.

CLECELL has plans to collaborate with researchers around the world to offer a testbed for the research of viruses and the development of cures, with plans to carry out research not only on virus infection, but also drug delivery, toxicity, and inflammation.

Furthermore, CLECELL claims that its proprietary 3D bioprinter, the U-FAB, is slated for tissue engineering research at the Boston Bioprinting Consortium, which is comprised of world-class scholars from Boston’s universities and hospitals and consists of eight joint-research teams.

“Despite the various existing methods of testing respiratory viruses in vitro, we require a more effective platform for testing,” indicated Young-Jae Cho, a professor at the Department of Pulmonology at Seoul National University Bundang Hospital. “The creation of precise artificial respiratory models through 3D bioprinting technology offers a potential alternative.”

The startup’s bioprinting technology could provide solutions for tissue engineers and life scientists to research and develop biomimetic human tissues and organs. Since its origin, the company has been researching and developing various reconstructed human skin models using scalable 3D bioprinting technology, focusing on building and implementing transplantable biomimetic human skin in the future.

Along with the U-FAB, the company has two other printing platforms: U-Printer for the development of artificial tissues and organs and U-Skin for reconstructing artificial human skin models. Through their U-Printer prototype, they have created artificial skin models, which they consider superior to the existing commercial ones as they are able to retain the shape and dimension without shrinking throughout the culture period and pigmentation, and this was realized by 3D bioprinting melanocytes without UV or chemical stimulation.

A need for hastening change has been at the center of many technological revolutions, and in these uncertain times, it seems imperative to rely on bioprinting technology that can accelerate results. CLECELL’s revolutionizing respiratory epithelium model could become a fundamental resource for vaccine testing. Never before have so many of the world’s researchers focused so urgently on a single topic. With so many minds mobilizing to understand the disease, this emerging powerful technology developed by the South Korean startup could reduce the time towards finding a cure for COVID-19.

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Scientific discoveries and research missions beyond Earth’s surface are quickly moving forward. Advancements in the fields of research, space medicine, life, and physical sciences, are taking advantage of the effects of microgravity to find solutions to some big problems here on Earth. Researchers in 3D printing and bioprinting have taken advantage of space facilities that are dedicated to conducting multiple experiments in orbit, such as investigating microgravity’s effects on the growth of three-dimensional, human-like tissues, creating high-quality protein crystals that will help scientists develop more effective drugs, and even growing meat with 3D printing technology.

The BioFabrication Facility (BFF) by Techshot and nScrypt (Credit: Techshot)

On November 2, 2019, a Northrop Grumman Antares rocket successfully launched a Cygnus cargo spacecraft on a mission to the International Space Station (ISS). The payload aboard the Cygnus included supplies for the 3D BioFabrication Facility (BFF), like human cells, bioinks, as well as new 3D printed ceramic fluid manifolds that replaced the previously used that were printed out of polymers. According to Lithoz – the company behind the 3D printed ceramic fluid manifolds – they are enabling advancements in bioprinting at the ISS.

The additive manufactured ceramics have been in service since November 2019 and Lithoz claims they have proven to provide better biocompatibility than printed polymers, resulting in larger viable structures.

Lithoz, a company specializing in the development and production of materials and AM systems for 3D printing of bone replacements and high-performance ceramics, printed the ceramic manifolds using lithography-based ceramic manufacturing (LCM) on a high-resolution CeraFab printer in collaboration with Techshot, one of the companies behind the development of the BFF. Moreover, the ceramic fluid manifolds are used inside bioreactors to provide nutrients to living materials in space by the BFF.

Testing of the ceramic 3D printed manifolds is focusing on biocompatibility, precision, durability, and overall fluid flow properties; and the latest round of microgravity bioprinting in December yielded larger biological constructs than the first BFF attempts in July.

NASA engineer Christina Koch works with the BioFabrication Facility in orbit (Credit: NASA)

Techshot and Lithoz engineers and scientists worked together to optimize the design and the manufacturing processes required to make it. Techshot Senior Scientist Carlos Chang reported that “it’s been an absolute pleasure working with Lithoz.”

While Lithoz Vice President Shawn Allan suggested that “their expertise in ceramic processing really made these parts happen. The success of ceramic additive manufacturing depends on working together with design, materials, and printing. Design for ceramic additive manufacturing principles was used along with print parameter control to achieve Techshot’s complex fluid-handling design with the confidence needed to use the components on ISS.”

Headquartered in Vienna, Austria, and founded in 2011, Lithoz offers applications and material development to its customers in cooperation with renowned research institutes all over the world, benefiting from a variety of materials ranging from alumina, zirconia, silicon nitride, silica-based for casting-core applications through medical-grade bioceramics.

This work, in particular, highlighted an ideal use case for ceramic additive manufacturing to enable the production of a special compact device that could not be produced without additive manufacturing while enabling a level of bio-compatibility and strength not achievable with printable polymers. Lithoz reported that Techshot engineers were able to interface the larger bio-structures with the Lithoz-printed ceramic manifolds and that the next steps will focus on optimized integration of these components and longer culturing of the printed biological materials. While conditioned human tissues from this mission are expected to return to Earth in early 2020 for evaluation.

Back in July 2019, Gene Boland, chief scientist at Techshot, and Ken Church, chief executive officer at nScrypt, discussed the BFF at NASA’s Kennedy Space Center in Port Canaveral, Florida, how they planned to use the BFF in orbit to print cells (extracellular matrices), grow them and have them mature enough so that when they return to Earth researchers can encounter a close to full cardiac strength. Church described how a tissue of this size has never been grown here on Earth, let alone in microgravity. The 3D BFF is the first-ever 3D printer capable of manufacturing human tissue in the microgravity condition of space. Utilizing adult human cells (such as pluripotent or stem cells), the BFF can create viable tissue in space through a technology that enables it to precisely place and build ultra-fine layers of bioink – layers that may be several times smaller than the width of a human hair – involving the smallest print nozzles in existence.

Flight engineer Andrew Morgan works with the BioFabrication Facility (Credit: NASA)

Experts suggest that bioprinting without gravity eliminates the risk of collapse, enabling organs to grow without the need for scaffolds, offering a great alternative to some of the biggest medical challenges, like supplying bioprinted organs, providing a solution to the shortage of organs.

With NASA becoming more committed to stimulating the economy in low-Earth orbit (LEO), as well as opening up the ISS research lab to scientific investigations and experiments, we can expect to learn more about some of the most interesting discoveries that could take place 220 miles above Earth. There are already quite a few bioprinting experiments taking place on the ISS, including Allevi and Made In Space’s existing Additive Manufacturing Facility on the ISS, the ZeroG bio-extruder which allow scientists on the Allevi platform to simultaneously run experiments both on the ground and in space to observe biological differences that occur with and without gravity, and CELLINK‘s collaboration with Made In Space to identify 3D bioprinting development opportunities for the ISS as well as for future off-world platforms. All of these approaches are expected to have an impact on the future of medicine on Earth.

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