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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KFC Russia Explores 3D Printing Chicken

Considering the amount of time that scientists have spent lately engineering human tissue in the lab, it’s not surprising to hear that restaurant chains want to get in on the action to replace the expense of raising animals for meat. And while you may be trying to imagine how 3D printed meat would be displayed on a KFC menu board, the “powers at be” at KFC are still busy at the drawing board—collaborating with 3D Bioprinting Solutions.

3D printed food is always a shoo-in for garnering excitement, feeding our appetites with potential for the future, whether targeting meat, breakfast, cake, or other items that can be easily extruded.

A variety of different companies have been interested in redefining meat, but often with a plant-based concept. 3D printing enthusiasts, technology buffs, and curious consumers may be interested in finding out more about the techniques and the materials, but still balk at becoming anything close to a vegetarian (or god forbid, a vegan!).

3D printing actual meat has historically been more challenging—along with the overall concept of any type of tissue engineering. The KFC announcement could be more gimmick than true intent, but for now they seem to be exploring the benefits of more environmentally friendly production, better nutrition, and the possibility of eliminating chicken farms (and all the associated flak from activists—as well as consumers who are just generally disgusted).

The process of creating chicken in a lab, dubbed “craft meat,” could mean reducing emissions exponentially as well as freeing up large tracts of land currently required to raise animals.

“The production of cell meat products is the next step in the development of our concept of the restaurant of the future,” explained Raisa Polyakova, KFC CEO in Russia.

Only time will tell whether there is a true market for bioprinted chicken, with success in the lab waiting to be seen, as well as popularity with the Russian fast-food palate. Polyakova is confident that they may be able to pioneer new technology that can be shared with the rest of the world, perhaps transforming menus everywhere one day. Savings on the bottom line could play an enormous role too—not only allowing for chains like KFC to save substantially in production, but also passing that down to consumers who are tired of over-paying for sandwiches, burgers, and most items available in contemporary drive-thrus.

“Technologies based on 3D bioprinting, which were initially widely recognized in medicine, today are gaining more and more popularity in the field of food production, such as, for example, animal meat. The rapid development of such technologies in the future will make meat products printed on a 3D bioprinter more affordable,” said Yousef Hesuani, co-founder and managing partner of 3D Bioprinting Solutions.

[Source / Images: popmech]

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3D Printed Medicine Uses Fish Gelatin to Deliver Cancer Treatment

Japanese researchers Jin Liu, Tatsuaki Tagami, and Tetsuya Ozeki have completed a recent study in nanomedicine, releasing their findings in “Fabrication of 3D Printed Fish-Gelatin-Based Polymer Hydrogel Patches for Local Delivery of PEGylated Liposomal Doxorubicin.” Experimenting with a new drug delivery system, the authors report on new potential for patient-specific cancer treatment.

The study of materials science continues to expand in a wide range of applications; however, bioprinting is one of the most exciting techniques as tissue engineering is expected to lead to the fabrication of human organs in the next decade or so. Such research has also proven that bioprinting may yield much more powerful drug delivery whether in using hybrid systems, multi-drug delivery systems, or improved scaffolds.

Here, the materials chosen for drug delivery are more unique as the researchers combined printer ink with semi-synthesized fish gelatin methacryloyl (F-GelMA)—a cold fish gelatin derivative.

In providing aggressive cancer treatment to patients, the use of doxorubicin (DOX) is common as an anti-carcinogen for the treatment of the following diseases:

  • Breast cancer
  • Bladder cancer
  • Kaposi’s sarcoma
  • Lymphoma
  • Acute lymphocytic leukemia

DOX may also cause serious cardiotoxicity, however, despite its use as a broad-spectrum drug. As a solution, PEGylated liposomal DOX, Doxil has been in use for treatment of cancer with much lower cardiotoxity. The nanomedicine has also been approved by the FDA, and is used for targeting local tumors; for instance, this type of drug delivery system could be suitable for treating a brain tumor.

“PEGylating liposomes can prolong their circulation time in blood, resulting in their passive accumulation in cancer tissue, called the enhanced permeability and retention effect,” state the authors.

Using a 3D bioprinter, the authors developed liposomal patches to be directly implanted into cancerous cells.

(a) Synthesis of fish gelatin methacryloyl (F-GelMA). (b) Hybrid gel of cross-linked F-GelMA and carboxymethyl cellulose sodium (CMC) containing PEGylated liposome. The reaction scheme was prepared in previous studies

“We used a hydrogel containing semi-synthetic fish-gelatin polymer (fish gelatin methacryloyl, F-GelMA) to entrap DOX-loaded PEGylated liposomes. Fish gelatin is inexpensive and faces few personal or religious restrictions,” stated the authors.

Fish gelatin has not been used widely in bioprinting, however, due to low viscosity and rapid polymerization. To solve that problem, the authors created a bioink composite with elevated viscosity.

Viscous properties of drug formulations used as printer inks. (a) The appearance of F-GelMA hydrogels containing different concentrations of CMC. (b) The viscosity profiles of F-GelMA hydrogels containing different concentrations of CMC. The data represent the mean ± SD (n = 3).

And while hydrogels are generally attractive for use due to their ability to swell, for this study, the researchers fabricated a variety of different materials—with the combination of 10% F-GelMA and 7% carboxymethyl cellulose sodium (a thickening agent) showing the highest swelling ratio.

Swelling properties of hydrogels after photopolymerization. (a) Swelling ratio of different concentrations of F-GelMA. (b) Swelling ratio of mixed hydrogel (10% F-GelMA with different concentrations of CMC). The data represent the mean ± SD (n = 3).

Design of the different 3D geometries: (a) cylinder, (b) torus, and (c) gridlines.

Patches were printed in three different sample shapes, using a CELLINK bioprinter syringe as the authors tested drug release potential in vivo. Realizing that surface area, crosslinks density, temperature, and shaker speed would play a role, the team relied on a larger surface volume for more rapid release of drugs.

Printing conditions of patches.

While experimenting with the torus, gridline, and cylindrical sample patches, the researchers observed gridline-style patches as offering the greatest potential for sustained release.

Drug release profiles of liposomal doxorubicin (DOX). (a) Influence of shape on drug release. The UV exposure time was set to 1 min. (b) Influence of UV exposure time on drug release. The gridline object was used for this experiment. The data represent the mean ± SD (n = 3).

“These results indicate that CMC is useful for adjusting the properties of printer ink and is a useful and safe pharmaceutical excipient in drug formulations. We also showed that drug release from 3D-printed patches was dependent on the patch shapes and UV exposure time, and that drug release can be controlled. Taken together, the present results provide useful information for the preparation of 3D printed objects containing liposomes and other nanoparticle-based nanomedicines,” concluded the authors.

[Source / Images: ‘Fabrication of 3D Printed Fish-Gelatin-Based Polymer Hydrogel Patches for Local Delivery of PEGylated Liposomal Doxorubicin’]

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Rice Researchers 3D Print with Lasers and Sugar to Build Complex Vascular Networks

A team of researchers from Rice University has uncovered a promising strategy to generate vascular networks, one of the most daunting structures in the human body. Using powdered sugar and selective laser sintering, the researchers were able to build large structures from complex, branching, and intricate sugar networks that dissolve to create pathways for blood in lab-grown tissue.

This is the team’s latest effort to build complex vascular networks for engineered tissues to show that they could keep densely packed cells alive for two weeks. The findings of their study—published in the Nature Biomedical Engineering journal—prove that developing new technologies and materials to mimic and recapitulate the complex hierarchical networks of vessels gets them closer to providing oxygen and nutrients to a sufficient number of cells to get a meaningful long-term therapeutic function.

“One of the biggest hurdles to engineering clinically relevant tissues is packing a large tissue structure with hundreds of millions of living cells,” said study lead author Ian Kinstlinger, a bioengineering graduate student at Rice’s Brown School of Engineering. “Delivering enough oxygen and nutrients to all the cells across that large volume of tissue becomes a monumental challenge. Nature solved this problem through the evolution of complex vascular networks, which weave through our tissues and organs in patterns reminiscent of tree limbs. The vessels simultaneously become smaller in thickness but greater in number as they branch away from a central trunk, allowing oxygen and nutrients to be efficiently delivered to cells throughout the body.”

Overcoming the complications of 3D printing vascularization has remained a critical challenge in tissue engineering for decades, as only a handful of 3D printing processes have come close to mimic the in vivo conditions needed to generate blood vessels. Without them, the future of bioprinted organs and tissues for transplantation will remain elusive. Many organs have uniquely intricate vessels, like the kidney, which is highly vascularized and normally receives a fifth of the cardiac output, or the liver, in charge of receiving over 30% of the blood flow from the heart. By far, kidney transplantation is the most common type of organ transplantation worldwide, followed by transplants of the liver, making it crucial for regenerative medicine experts to tackle vascularization.

Ian Kinstlinger with a blood vessel template he 3D printed from powdered sugar (Credit: Jeff Fitlow/Rice University)

In the last few years, extrusion-based 3D printing techniques have been developed for vascular tissue engineering, however, the authors of this study considered that the method presented certain challenges, which led them to use a customized open-source, modified laser cutter to 3D print the sugar templates in the lab of study co-author Jordan Miller, an assistant professor of bioengineering at Rice.

Miller began work on the laser-sintering approach shortly after joining Rice in 2013. The 3D printing process fuses minute grains of powder into solid 3D objects, making possible some complex and detailed structures. In contrast to more common extrusion 3D printing, where melted strands of material are deposited through a nozzle, laser sintering works by gently melting and fusing small regions in a packed bed of dry powder. According to Miller, “both extrusion and laser sintering build 3D shapes one 2D layer at a time, but the laser method enables the generation of structures that would otherwise be prone to collapse if extruded.”

“There are certain architectures—such as overhanging structures, branched networks and multivascular networks—which you really can’t do well with extrusion printing,” said Miller, who demonstrated the concept of sugar templating with a 3D extrusion printer during his postdoctoral studies at the University of Pennsylvania. “Selective laser sintering gives us far more control in all three dimensions, allowing us to easily access complex topologies while still preserving the utility of the sugar material.”

Assistant professor of bioengineering at Rice University, Jordan Miller (Credit: Jeff Fitlow/Rice University)

Generating new 3D printing processes and biomaterials for vascularization is among the top priorities for the researchers at Miller’s Bioengineering Lab at Rice. The lab has a rich history of using sugar to construct vascular network templates. Miller has described in the past how sugar is biocompatible with the human body, structurally strong, and overall, a great material that could be 3D printed in the shape of blood vessel networks. His original inspiration for the project was an intricate dessert, even going as far as suggesting that “the 3D printing process we developed here is like making a very precise creme brulee.”

To make tissues, Kinstlinger chose a special blend of sugars to print the templates and then filled the volume around the printed sugar network with a mixture of cells in a liquid gel. Within minutes, the gel became semisolid and the sugar dissolved and flushed away to leave an open passageway for nutrients and oxygen. Clearly, sugar was a great choice for the team, providing an opportunity to create blood vessel templates because it is durable when dry, and it rapidly dissolves in water without damaging nearby cells.

A sample of blood vessel templates that Rice University bioengineers 3D printed using a special blend of powdered sugars. (Credit: B. Martin/Rice University)

In order to create the treelike vascular architectures in the study, the researchers developed a computational algorithm in collaboration with Nervous System, a design studio that uses computer simulation to make unique art, jewelry, and housewares that are inspired by patterns found in nature. After creating tissues patterned with these computationally generated vascular architectures, the team demonstrated the seeding of endothelial cells inside the channels and focused on studying the survival and function of cells grown in the surrounding tissue, which included rodent liver cells called hepatocytes.

The hepatocyte experiments were conducted in collaboration with the University of Washington (UW)’s bioengineer and study co-author Kelly Stevens, whose research group specializes in studying these delicate cells, which are notoriously difficult to maintain outside the body.

“This method could be used with a much wider range of material cocktails than many other bioprinting technologies. This makes it incredibly versatile,” explained Stevens, an assistant professor of bioengineering in the UW College of Engineering, assistant professor of pathology in the UW School of Medicine and an investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine.

The results from the study allowed the team to continue their work towards creating translationally relevant engineered tissue. Using sugar as a special ingredient and selective laser sintering techniques could help advance the field towards mimicking the function of vascular networks in the body, to finally deliver enough oxygen and nutrients to all the cells across a large volume of tissue.

Miller considered that along with the team they were able to prove that “perfusion through 3D vascular networks allows us to sustain these large liverlike tissues. While there are still long-standing challenges associated with maintaining hepatocyte function, the ability to both generate large volumes of tissue and sustain the cells in those volumes for sufficient time to assess their function is an exciting step forward.”

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Cellink Teams with Lonza to Advance Bioprinting Cell Cultures

For over four years biotech company Cellink has been helping researchers pursue creative ways to promote organ regeneration, test novel drugs, develop vascularized bioconstructs, and more. Through collaborative partnerships and pioneering research, the firm has quickly become a market leader for cell-based applications. Along that road, they have partnered with several startups and multinationals to open up a broader range of possibilities in the field. Their latest partnership with Lonza—a leading suppliers to the pharmaceutical, biotech, and specialty ingredients markets—will provide researchers and scientists with even more options to enhance bioprinting of complex 3D human tissue constructs.

The companies have joined forces to offer a comprehensive 3D bioprinting solution designed to optimize and increase access to complete 3D cell culture workflows. The solution integrates Cellink’s 3D bioprinting instruments and pioneering commercial bioinks with Lonza’s broad selection of human-derived primary cells and supporting culture media.

Credit: Lonza

“Everything we do at CELLINK, from live cell imaging to our innovative bioprinting systems and bioinks, is meant to support our customers with the products and services needed for them to more effectively and efficiently research solutions to some of the most important challenges of our time. Challenges such as cancer therapeutics, regenerative medicine and the testing and development of drugs, to name a few,” said Ginger Lohman, Biodispensing Product Manager at Cellink’s Gothenburg headquarters in Sweden. “When it came time to expand our portfolio into complete 3D cell culture workflows, we knew it was critical that we brought the right partner onboard. We’re confident that Lonza is that partner.”

According to Cellink, cell biologists will now be able to rely on a high-performing product portfolio to successfully execute some of the most demanding work on 3D bioprinting and boost their scientific research. The proposed solution under the partnership combines Cellink’s 3D bioprinting instruments and bioinks with Lonza’s primary cells and culture media, to meet the needs of cell biologists for enhanced bioprinting of complex 3D human tissue constructs.

Since the origins of cell culture more than a century ago, cells have been cultured in two-dimensions; however, 3D cell culture has proven to be a better model for representing in vivo conditions, offering a more accurate and reliable means of predicting and analyzing cell behavior. In fact, it has proven to be a great enabler for scientists to handle cells in vitro while obtaining results that are closer to the in vivo environment without relying on animals, thereby avoiding many ethical issues.

With so many benefits, 3D cell cultures are being widely adopted in numerous laboratories—even more so as researchers look to create increasingly complex 3D constructs and find solutions to structural and material engineering challenges. For years, Swiss-based Lonza has been developing the building blocks needed to create 3D cell culture models, offering an extensive array of human-derived primary cells and culture media, ethically sourced and authenticated thorough quality control testing.

Robust, viable cells are an essential component of any successful cell culture application, and so is 3D bioprinting. A big part of the 3D cell culture workflow involves 3D bioprinting, which is thriving as a powerful technology for engineering complex 3D tissues for in vitro drug discovery research. Cellink is currently providing a wide range of 3D bioprinting systems, like INKREDIBLE, Bio X6 systems, and LumenX, which stems from a collaboration with Volumetric, a startup established by Rice University professor Jordan Miller. Furthermore, since 2016, the company has successfully commercialized the world’s first universal bioink designed to print complex 3D human tissue constructs with any 3D bioprinting system. The biomaterial is useful for scientists as it can be modified with peptides and growth factors to develop a series of customized bioink formulations to meet varying application needs and is used in hundreds of labs around the world.

Cellink’s INKREDIBLE system (Credit: Cellink)

“Cell biology laboratories are constantly seeking innovative new technologies to enhance their experimental workflows and help deliver on their promise to drive the next research breakthrough,” explained Katrin Hoeck, head of marketing for Cell Analysis and Testing Solutions at Lonza. “Our broad panel of human-derived primary cells is specifically engineered to enable researchers to develop biological in vitro model systems that more closely reflect disease biology. This new collaboration with Cellink will enable our customers to build physiologically relevant 3D models to accelerate target identification/validation, investigation of mechanisms of action and safety testing in drug discovery.”

Under the agreement, Cellink will provide this complete solution through its global sales channels, supported by Lonza’s well-established logistics processes.

This is not the first partnership with the pharma industry for Cellink. The company also recently announced a collaboration with AstraZeneca, the British-Swedish multinational pharmaceutical and biopharmaceutical company, to utilize Cellink’s 3D bioprinting technology for liver organoid culture for drug discovery purposes in cardiovascular, renal and metabolic diseases.

According to Lonza, “The pharma and biomedical research laboratories are constantly seeking innovative new technologies to enhance their experimental workflows and help deliver on their promise to drive the next research breakthrough.” This collaboration could strengthen the processes and end products of research, offering substantial benefits for more predictive cell models and ultimately increasing the usefulness of 3D culturing cells for many applications in major areas of life sciences.”

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3D Printing Webinar & Virtual Event Roundup, May 31, 2020

With so many events going virtual due to the ongoing COVID-19 pandemic, there’s also been an increase in the number of webinars that companies in the additive manufacturing industry are holding. To make things easier for our readers, since there’s so much online content to choose from these days, 3DPrint.com is compiling all of these available webinars, and the virtual events, into a weekly roundup for you, starting today.

Freeman Technology Webinar

Characterization Tools for Evaluating Polymer Powders for Laser Sintering Webinar

This Tuesday, June 2nd, UK-based Freeman Technology, a Micromeritics company that creates systems for measuring the flow properties of powder materials, will host a webinar at 9 am ET titled “Characterization Tools for Evaluating Polymer Powders for Laser Sintering.” Enrico Gallino, Senior Engineer – Material Specialist at Ricoh UK Products Ltd, will speak about evaluating an AM powder characterization methodology, and will also discuss the results of screening the relevant properties, such as flowability, shape, and thermal properties, of a variety of materials.

“As additive manufacturing (AM) technology transitions from the fabrication of prototypes to serial production of end-use parts, the understanding of the powder properties needed to reliably produce parts of acceptable quality becomes critical,” the webinar site states.

“Achieving the optimal quality for parts does not only depend on setting the right process parameters. Material feedstock also plays an important role when aiming for high performance products. In the case of selective laser sintering, polymer powders are used as a raw material. Therefore, controlling the quality and correctly characterizing the particles used in the process is a key step to successfully apply polymer AM techniques and also to expand the range of material that can be process with this technology.”

Click here to register.

Dassault Systèmes Webinar

Dassault Systèmes be will holding a live webinar on Thursday, June 4th at 10 am ET, titled “Intuitive 3D Designs with CATIA® and SOLIDWORKS® on Mobile Devices.” Participants will have the chance to learn how beneficial flexible design workflows can be when delivering products to market, faster, across many different industries. There will be a live demonstration, using tablets and PCs, on how combining CATIA and SOLIDWORKS on the 3DEXPERIENCE platform will allow your business to add engineering details with simple parametric modeling, create organic surfaces with subdivision (Sub-D) modeling, generate complex patterns and shapes quickly, optimize and evolve designs using an algorithmic approach, and more – all from your own device. The demonstration will be followed by a live Q&A session.

“Discover our portfolio of ready-to-go online Design and Engineering applications in action, which enable you to design from your laptop, your smartphone or tablet! Enjoy increased agility without compromising best-in-class design and engineering capabilities,” the webinar site states.

“With its growing app portfolio and secure cloud technology, the 3DEXPERIENCE platform enables you to manage all facets of your product development process while reducing infrastructure costs, IT overhead, software maintenance and complexity. All 3DEXPERIENCE solutions work together seamlessly making data management, sharing and collaboration easy.”

Click here to register.

3DHEALS 2020 Global Summit

The 3DHEALS conference is going virtual this year, as the 3DHEALS 2020 Global Summit runs from 11 am-9:30 pm ET June 5th and 6th. Offering powerful networking and effective programming on a global stage, this popular bioprinting conference – sponsored by Whova and Zoom – brings together influencers and audiences from over nine countries, offering opportunities and insights that can be beneficial to stakeholders. With over 70 speakers, more than four workshops, startup events, simulated in-conference experience, an interview series hosted by Dr. Jenny Chen, and more, this is one you won’t want to miss.

“3DHEALS2020 is designed to cater to a wide range of professionals, ranging from healthcare early adopter, manufacturers, engineers, legal professionals and policymakers, C-Level executives, entrepreneurs, investors, and more. We aim to create an effective program that maximizes the attendee’s experiences and decreases the barriers in communication among stakeholders,” the event site states.

Click here to register.

Will you attend these events and webinars, or have news to share about future ones? Let us know! Discuss this and other 3D printing topics at 3DPrintBoard.com or share your thoughts in the comments below.

The post 3D Printing Webinar & Virtual Event Roundup, May 31, 2020 appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

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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New Facility for Bioengineering Research Opens in Los Angeles

In a world eager to solve the problem of rejection in organ transplantation, a young American scientist developed a breakthrough test in 1964 that would help establish the compatibility of tissue types between organ donors and patients in need of transplants. Even though, today, efforts to meet organ transplant demand are shifting toward the field of bioengineering, as researchers search for ways to recreate complex organs with patient-derived cells, the legacy of that scientist, Paul Ichiro Terasaki, continues to inspire discoveries in transplant medicine through his philanthropic ventures.

The Terasaki Institute for Biomedical Innovation (TIBI), a nonprofit research organization established by Terasaki, professor emeritus of surgery at the David Geffen School of Medicine at the University of California Los Angeles (UCLA), will open the doors to a new facility in 2022. The newly-acquired addition will house interdisciplinary research in bioengineering, micro- and nanoscale technologies to enable transformative biomedical innovation as part of continuing research to solve the biggest problems related to organ transplantation and beyond.

Earlier this month, the Terasaki Institute announced the revamping of a building in the Woodland Hills area of the city of Los Angeles. Once home to the Weider Health and Fitness Center, created by bodybuilder and entrepreneur Joe Weider, the two-story building will be custom-designed to house the latest technology in cutting-edge research and will provide 50,000 square feet of floor space for up to 200 employees.

Located just 22 miles north of the original Terasaki Institute facilities in Westwood, the new space devoted to laboratory research will be designed to accommodate multiple teams of scientists, who will be developing bioengineered systems, devices, and other products with several biomedical applications. This new facility will be fully equipped to enable such technologies as tissue engineering and regeneration, biofabrication using 3D printing, nano- and micro-engineering, stem cell engineering, and the creation of human organs on chips.

When the new facility is inaugurated, with the renovation of the building set to begin in fall 2020, it will become the Terasaki Institute’s third research facility. In addition to the ample space and unique design features of the laboratory, the new facility will include in-house technology translation capabilities to be able to build prototypes and scale models of devices engineered by the institute. It will also be able to accommodate meetings, seminars, and conferences to further the education and exchange of ideas among its researchers and collaborators.

“I’m very excited about the addition of the new building to the Terasaki Institute. I believe that this addition will give us needed research space to bring together a number of leading scientists in our efforts to develop the next generation of biomedical innovations,” said Terasaki Institute’s new director and CEO, Ali Khademhosseini. “I’m particularly excited about furthering the great legacy of the Weider family and the building’s history in promoting health and fitness by focusing on individualized cures and diagnostics.”

Previously at Harvard Medical School, the Wyss Institute for Biologically Inspired Engineering, and most recently at UCLA Bioengineering, Khademhosseini has been an influential figure in pushing bioengineering forward. His research in regenerative medicine, tissue engineering, and micro- and nanotechnologies for the treatment of diseases has been related to advancements that allow reprogramming of adult cells to become progenitors, as well as editing genes. The bioengineer has also created a technique that uses a specially adapted 3D printer that could help advance the field of regenerative medicine by making it possible to 3D print complex artificial tissues on demand. He has also established the Khademhosseini Lab, an industry-leading tissue engineering lab that is co-sponsored by both MIT and Harvard and acts as a strategic partner to 3D bioprinting startup BioBots.

Ali Khademhosseini (Image: Ali Khademhosseini)

Stewart Han, president of the Terasaki Institute, has been working hard overseeing the planning and renovation of the new building: “It is exciting to be able to create a brand-new laboratory and research facility from the ground up, and it will greatly enhance our research capabilities when it’s completed. We also know that the new building will facilitate the future growth of our institute.

Founded in 2001, the Terasaki Institute was made possible through an endowment from the late Paul Terasaki, and it is expected to continue leveraging scientific advancements that enable an understanding of personalized medicine, from the macroscale of human tissues down to the microscale of genes, as well as to create technological solutions for some of the most pressing medical problems of our time.

Paul Terasaki in front of the Terasaki Life Sciences Building UCLA. (Image: Leslie Barton/UCLA)

“The board of the Terasaki Institute is very excited about the purchase of the new building in Woodland Hills, and we look forward to developing it into a world-class biomedical research center,” said board chair and diagnostic radiology specialist Keith Terasaki. “My father, the late Paul I. Terasaki, started the Terasaki Institute in hopes that it will make impactful discoveries in medical research. This new research facility will enable us to do so.”

To the field of transplant surgery, transplant pioneer Paul Terasaki enabled a broad understanding of organ transplant outcomes around the world. More than 70 years after his original discovery, patients still rely on organ donor transplants and the fundamentals of Terasaki’s laboratory developed tissue typing tests are still used today for the determination of transplant compatibility. Nonetheless, the Terasaki Institute envisions a world where personalized medicine is available to all. So, as the researchers at the institute continue to address the challenges that can finally advance the field of organ transplants from human donors to bioengineered artificial organs, they might bridge the gap between sickness and health. With one of the most productive 3D printing researchers as director, Khademhosseini, and a new facility to further explore biofabrication technology, we can expect to hear much more from the Terasaki Institute in years to come.

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3D Printing Review in Drug Delivery Systems: Pharmaceutical Particulates and Membranes

Researchers from Egypt, India, and the UK are studying the role of 3D printing in drug delivery systems. Their findings are detailed in the recently released ‘Pharmaceutical Particulates and Membranes for the Delivery of Drugs and Bioactive Moleclules,’ as they review new trends and developments.

In reviewing twelve different papers on the subject of pharmaceutical particulates and membranes, the researchers also collaborated with experts regarding design, materials, and applications; for instance, in a study by Kumar et al. [2], the researchers learned of an extended release drug delivery system for nicotine that shows potential for Parkinson’s disease interventions:

“These have been developed in the form of membranes with minimal rates of matrix degradation and retarding nicotine release. This has led to the zero-order release for 50 days following exposure to simulated cerebrospinal fluid (CSF),” stated the researchers.

Mora-Espíet et al. [3] have explored the targeting of microparticles and culturing breast cancer cell lines. Huang et al. [4] confirmed a new process for accelerating drug dissolution with ibuprofen-loaded hydroxypropyl methylcellulose nanoparticles.

Immunofluorescence analysis by confocal laser scanning microscope (CLSM) of cells cultured in static conditions. Confocal images of D492 and D492HER2 cells cocultured in static conditions and incubated with microparticles biofunctionalized with a non-specific secondary antibody (µP-secAb) or a specific anti-HER2 antibody (µP-antiH). Cells, constitutively expressing green fluorescent protein (GFP, green), were incubated with Alexa Fluor® 546 Phalloidin (red) to label actin microfilaments and Alexa Fluor® 405 conjugate secondary antibody (blue) to label HER2 in the plasma membrane. The arrows point to some examples of µPs located inside the cells. From ‘Cell Internalization in Fluidic Culture Conditions Is Improved When Microparticles Are Specifically Targeted to the Human Epidermal Growth Factor Receptor 2 (HER2).’

“During this process, it was shown that a key parameter, i.e., the spreading angle of atomization could provide a linkage among the working process, the property of generated nanoparticles and their functional performance,” stated the researchers. “They confirmed that the nanoparticle diameter (prepared based on a modified technique) has a profound influence on the drug release performance.”

Shah et al. [5] contributed a study as they moved forward to refine the effectiveness of moxifloxacin, an antibiotic used to treat a variety of bacterial infections. With a new system for optimizing nanoemulsion, they were able to ‘enhance the therapeutic effects of moxifloxacin,’ resulting in safe delivery.

Another development, contributed by Wan et al. [6], allowed for sustained release of loxoprofen sodium (LXP), with the addition of a unique coating:

“Their results identified both the citric acid (CA) and ADEC as the dissolution and diffusion-rate controlling materials significantly decreasing the drug release rate,” stated the researchers. “The optimal formulation for a pH-independent drug release in media has been suggested as at a pH above 4.5 and at slightly slow release in acid medium.”

“The pharmacokinetic studies have revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets has been achieved, with a relative bioavailability of 87.16% compared with the conventional tablets.”

Studying magnetic nanoparticles, Iglesias et al. [7] stated that BMNPs (biometic) were superior to MNPs (inorganic) for drug loading of molecules ‘positively charged at neutral pH.’ MNPs, however, have the potential for suitable transport abilities while under a magnetic field. Savin et al [8] explored gel formulations for skin melanoma treatment, along with fabricating breast cancer cells in 3D models—following one of the major trends in medicine today using models for treatment, training, and surgical planning too.

“The in vitro results for the tested CD-NHF-loaded gel formulations have revealed that the new composites can affect the number, size, and cellular organization of spheroids and impact individual tumor cell ability to proliferate and aggregate in spheroids,” stated the researchers.

Guadarrama-Acevedo et al. [9] created a new wound dressing made of alginate membrane and polycaprolactone nanoparticles, loaded with curcumin for healing. Integrating nanocarriers allows for drug permeation into multiple layers of skin, thus eliminating solubility issues with curcumin. Rancan et al. [10] performed research showing that after six hours, nanofiber mats offer the best drug concentration upon delivery.

Morphology and porosity of alginate membranes. (a) Micrographs by scanning electronic microscopy of the alginate membrane surface (A, B, D, and E) and membrane thickness (C and F). Magnification of 100× for A, D; 220× in B, C, E and F; the scale bar is 100 μm; (b) pore diameter and membrane thickness of M4 and CNp‒M4 membranes, mean ± SE, n = 3. * indicates that p < 0.05 is statistically significant. From ‘Development and Evaluation of Alginate Membranes with Curcumin-Loaded Nanoparticles for Potential Wound-Healing Applications.’

Further, Lian et al. [11] developed a system for using red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) to eliminate toxicity of ATO. Their work also showed that RSANS have lower levels of cytotoxicity, upon comparison with normal cells; RSANS also displayed antitumor effects on NB4 cells and 7721 cells.

Adeleke et al. [12] developed an isoniazid suspension as an antitubercular agent against TB, offering extended release:

RDS has been dispersible and stable in the dried and reconstituted states over 4 months and 11 days respectively, under common storage conditions.

Representative graphs displaying: (a) particle size distribution, (b) zeta potential distribution, as well as TEM micrographs showing different surface topographies and characteristics of the reconstitutable dry suspension (RDS) particles at different scales: (c) 1μm and (d) 5 μm, respectively. ‘Development and Evaluation of a Reconstitutable Dry Suspension Containing Isoniazid for Flexible Pediatric Dosing.’

“The published papers are also being compiled as an edited e-book, to be published by MDPI,” stated the researchers.

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: ‘Pharmaceutical Particulates and Membranes for the Delivery of Drugs and Bioactive Moleclules’]

 

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3DHEALS2020: A Not So Lonely Planet

Only a few weeks away from 3DHEALS2020, and I just got off the phone with one of our speakers, Dr. Ho, from NAMIC Singapore. Our brief interview reminded me just how much I enjoyed Singapore—its start-up like government, incredible universities, and its beautiful modern architecture, chili crabs, and unpredictable rainstorms. Now, I’m on my way to some of the best meals in my life with another 3DHEALS community event in a foreign city. Looking back, there are many stories like that: in Detroit, Vigo, Paris, Shanghai, or Boston, my work with 3DHEALS communities has been a journey of adventures and friendships. 3DHEALS2020 is really a way to summarize my travels from the last two years. It is my version of Lonely Planet—the healthcare 3D printing version.

I really felt more alive when people have welcomed me into their cities; when they have showed off their latest innovations; when they have bantered enthusiastically with one another in a local pub till midnight after 3DHEALS events. And they felt the same way.

Sadly, however, this pandemic is putting old methods of human connection into question. Perhaps, a virtual summit is a stopgap solution for conferences, but, more likely, it is time for us to explore alternative and better ways to stay connected and informed.

The virtual 3DHEALS2020 summit will be a good start.

While we can’t serve you delicious San Francisco Blue Bottle coffee, there are three things we aim to do right with this conference:

1. Awesome live content

One upside about the virtual summit is that people who could not be available due to logistic barriers are now more available. We added 20+ speakers since the pandemic began and are still adding more parallel workshops to the existing program. Some of highlights include:

A. Biofabrication/Bioprinting Panels and Workshops:

Welcome to the holy grail of healthcare 3D printing applications!

These panels and workshops collect some of the brightest minds in the world of tissue engineering, biofabrication, and bioprinting. It includes the newest generation of startup founders. Names such as Stephanie WillerthAdam FeinbergJordan Miller are already well-established and loved in the scientific communities and just founded their own startups within the last 12 months. More established startup founders whose companies are also critical to the eventual success of biofabrication, tissue engineering, and cell therapy at large will also join us live, including Melanie Mathieu from Prellis Biologics, Jon Rawley from Roosterbio, John O’Reily from Xylyx, Taciana Pereira from Allevi, and Kevin Caldwell from Ossium Health. Qrquidea Garcia (“Orchid”) from JNJ Innovation will also join us on this panel, discussing how an industry leader can work with innovators and startups in this exciting, burgeoning field.

B. Regulatory and Legal Landscape of Healthcare 3D Printing

For those who put their skin in the game, this is probably one of the most must-attend sessions. 3D printing in healthcare is a super new field, and legal experts in this field who have established track records and legitimacy are only a handful. This session will include the most comprehensive list of legal and regulatory concerns specifically for healthcare 3D printing, including intellectual property/patent issues, product liability, FDA pathways, manufacturing standards, and more. Steven Bauer, from FDA CBER, just joined the panel to directly address concerns related to cell therapy from the biofabrication and stem cell communities. The speakers are not just well-versed on how to interpret the law and policies, but also how to interact with scientists, policy makers, organizations, and standards bodies at this early stage of the industry, with practical, real-life examples.

C. Global Perspectives

One lesson from this pandemic is that globalization has consequences. Having a well-rounded worldview of the global healthcare 3D printing ecosystem is a requirement for future success. Our early morning sessions are reserved for international speakers all over the world to meet the audience and share their unique perspectives, needs, and hopes. Both America Makes director John Wilczynski and NAMIC director Dr. Chaw Sing Ho, along with experts from Turkey, India, and Taiwan, will share how healthcare innovations can thrive in both local and global environments. On day two (June 6th), the audience will learn about how different countries are implementing the concept of 3D printing for Point of Care, which cannot be taken out of context of different healthcare systems and cultures. The audience will meet and learn from the leaders at UCSFStanfordGermany (Kumovis), India (Anatomiz3D), and developing countries.

2. Pre- and post-event networking opportunities

The attendees will have the opportunity to meet other attendees, speakers, and conference organizers as soon as they sign up the event using a dedicated conference app. They can send direct messages, post threads, share photos, host their own virtual events days before the conference. The app will be available to registered attendees for six months after the conference ends.

3. Entrepreneurship

One of the most exciting aspects of 3DHEALS2020 is its focus on entrepreneurship. Pitch3D has been a quarterly free and online pitch platform to selected early-stage startups in healthcare 3D printing and bioprinting spaces for the last two years, introducing 30+ startups from all over the world to institutional investors. 3DHEALS2020 also gathered some of the most experienced VCs and entrepreneurs in the space to share their stories, perspectives, and directly engage with the startups and the 3DHEALS2020 attendees directly during both pitch sessions and investor panels. There will be ten startups pitching each day at 5-6 PM PST. Interested startups can apply here.

This is the time of uncertainty and change.

Join us at 3DHEALS2020, connect with the world, and take control of your future. This is a Not So Lonely Planet.

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