CELLINK BIO X Archives - Perfect 3D Printing Filament

Aalto University Develops a Novel Bioink for Cardiac Tissue Applications

Finland is one of Europe’s most forested nations. Over 70 percent of the country’s boreal forest is covered with spruce, pine, downy birch, and silver birch. But beyond the splendor of the Finnish woodlands, all these trees have one thing in common, and that is nanocellulose. A light solid substance obtained from plant matter which comprises cellulose nanofibrils (CNF) and is considered a pseudo-plastic that possesses the property of specific kinds of gels that are generally thick in normal conditions. Overall, it is a very environmentally friendly and non-toxic substance that is compatible with the human body and has the potential to be used for a range of medical applications.

In 2018, the Department of Bioproducts and Biosystems at Aalto University, located just outside Helsinki, began searching for new ideas to revitalize one of the country’s traditional economic engines, forests (which are handled sustainably thanks to renewable forest resources). At the time, they noticed that one of the possible applications could be working with nanocellulose. Forward two years and the researchers have come up with a new bioink formulation praising nanocellulose at its basis.

Thanks to the structural similarity to extracellular matrices and excellent biocompatibility of supporting crucial cellular activities, nanocellulose-based bioprinting has clearly emerged for its potential in tissue engineering and regenerative medicine. The qualities of the generally thick and fluid light substance make it an excellent match to develop bioinks that are both suitable and scalable in their production, but also have consistent properties. However, there have been major challenges in processing nanocellulose.

As described by Aalto University researchers in a recently published paper in the science journal ACS Publication, the unresolved challenges of bioink formulations based on nanocelluloses are what stops the substance from becoming one of the preferred components for 3D bioprinting structures. This is why Finnish researchers focused on developing a single-component bioink that could be used to create scaffolds with potential applications in cardiac biomedical devices, while fundamentally dealing with some of the limitations of using nanocellulose-based bioinks.

A co-author of the paper and a doctoral candidate at Aalto’s Department of Bioproducts and Biosystems, Rubina Ajdary, told 3DPrint.com that “other than natural abundance and as a renewable resource, nanocellulose has demonstrated to have an outstanding performance in tissue engineering.” She also suggested that “recent efforts usually consider the use of nanocellulose in combination with other biopolymers, for example, in multicomponent ink formulations or to encapsulate nanoparticles. But we were interested in investigating the potential of monocomponent nanocellulose 3D printed scaffolds that did not require crosslinking to develop the strength or solidity.”

In fact, the Biobased Colloids and Materials (BiCMat) research group at Aalto University, led by Orlando Rojas, proposed heterogeneous acetylation of wood fibers to ease their deconstruction into acetylated nanocellulose (AceCNF). As a unique biomaterial opportunity in 3D scaffold applications, the team considered using nanocelluloses due to the natural, easy to sterilize, and high stability porosity of the substance, and chose to introduce AceCNF for the generation of 3D printed scaffolds for implantation in the human body. The team then went on to evaluate the interactions of the scaffolds with cardiac myoblast cells.

“Most modifications make the hydrogels susceptible to dimensional instability after 3D printing, for instance, upon drying or wetting. This is exacerbated if the inks are highly diluted, which is typical of nanocellulose suspensions, forming gels at low concentrations,” went on Ajdary. “This instability is one of the main reasons why nanocellulose is mainly combined with other compounds. Instead, in this research, we propose heterogeneous acetylation of wood fibers to ease their deconstruction into acetylated nanocellulose for direct ink writing. A higher surface charge of acetylated nanocellulose, compared to native nanocellulose, reduces aggregation and favors the retention of the structure after extrusion even in significantly less concentration.”

This is exactly why it was important for the researches to develop a single component bioink. Nanocellulose has shown promises when combined with other biopolymers and particles. However, Ajdary insists that benefits including similarity to the extracellular matrix, high porosity, high swelling capacity, ease of surface modification, and shear thinning behavior of cellulose, encouraged them to study the potential of monocomponent surface-modified nanocelluloses.

Acetylated nanocellulose (Credit: Aalto University School of Chemical Engineering)

The team at Aalto University used the sustainable and widely available nanocelluloses to make several formulations of bioinks and evaluate them, including unmodified nanocellulose CNF, Acetylated CNF (AceCNF), and TEMPO-oxidized CNF.

To 3D bioprint the hydrogels, researchers used Cellink bioprinters, something Ajdary attributed to the user-friendliness of the device and because it provided a lot of flexibility to test different types of hydrogels and emulsions produced in the research group.

In this new process, the single-component nanocellulose inks were first 3D printed into scaffolds using Cellink’s BIO X bioprinter, which is equipped with a pneumatic print head was used to extrude single filaments and form the 3D structures. Then freeze-dried to avoid extensive shrinkage, and sterilized under UV light. After sterilization the scaffold was ready and cells seeded on the samples.

“3D structures of acetylated nanocellulose are highly stable after extrusion in far less concentrations. The lower concentration in wet condition facilitates the scaffold with higher porosity after dehydration which can improve the cell penetration in the structure and assist in nutrient transport to the cells as well as in the transport of metabolic waste,” specified Ajdary.

The researchers claim that the method was successful as the 3D printed scaffolds were compatible with the cardiomyoblast cells, enabling their proliferation and attachment, and revealing that the constructs are not toxic. Although still in research stages, these bioinks and technique can be used for the inexpensive, consistent fabrication and storage of constructs that can be applied as base materials for cardiac regeneration.

What is novel in this study is the particular focus on single-component nanocellulose-based bioinks that open up a possibility for the reliable and scale-up fabrication of scaffolds appropriate for studies on cellular processes and for tissue engineering. Since this is an ongoing research, we can expect to read more published material from Aalto University researchers as they continue testing their unique technique even further.

Scaffolds corresponding to 3D printed AceCNF (Credit: Aalto University)

The post Aalto University Develops a Novel Bioink for Cardiac Tissue Applications appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

Polbionica Could Become the Next Success Story in Organ Bioprinting

Last year, a scientific team in Warsaw, Poland, bioprinted the world’s first prototype of a bionic pancreas with a vascular system. Led by clinical transplantation expert and inventor, Michał Wszoła, the specialists seek to introduce 3D bioprinting of the bionic pancreas to clinical practices worldwide in just over three years. The work, conducted at Polbionica, a spin-off company from the Foundation of Research and Science Development, will bring to market the research to 3D bioprint scaffolds using live pancreatic islands or insulin-producing cells to create a bionic pancreas, like the bioinks, bioreactor and the g-code files necessary to print bionic pancreas.

With more than 40 million people suffering from type I diabetes worldwide, this project holds a lot of promise. In Europe alone, seven million people are afflicted with the disease, with 700,000 of them undergoing serious complications.

The statistics alone offer a troubling overall pan of the disease. Even more so because, as Wszoła suggested in an interview with 3DPrint.com, hypoglycemia unawareness is a life-threatening complication that causes sudden death and is one of the major problems for type I diabetes; and the only method leading to a complete cure is a pancreas or pancreatic islet transplantation. But less than 200 pancreatic transplantations are carried out annually in Europe, which means that hundreds of people die while waiting for a transplant.

Polbionica is working to develop the key building blocks that support the development of the first bionic pancreas suitable for transplantation: bioink A for bioprinting bionic pancreas, bioink B for bioprinting vasculature, a novel bioreactor for growing organs, and a g-code file with specific bioprinting commands.

The company developed its own bioinks for this project and for bioprinting other organs of the body, while another bioink was used in 3D bioprinting of vessels with endothelial cells. Moreover, to carry out their research, they used Cellink‘s BioX bioprinter.

Bioreactor (Image: Polbionica)

According to Wszoła, the organ based on bioprinted 3D cell-laden bioinks, functional vessels, and pancreatic islets would restore the body’s ability to regulate blood sugar levels and revolutionize the treatment of diabetes.

For now, the scientific team has the ability to bioprint a living organ of 3x5x3.5 centimeters, which consists of more than 600,000 islets equivalent that are retrieved from the donor and considered to be the suitable amount to cure a person with diabetes.

“Our next step is to replace the pancreatic islets with stem cell-derived alpha and beta cells. With this approach, the patient would not have to wait for donor cells since the pluripotent stem cells being used are derived from their own tissues,” indicated Wszoła, who is also a transplant and general surgeon. “So far, studies on animals proved that the use of established products was safe.”

Scientists at work at the lab (Image: Polbionica)

“In order to reverse diabetes in humans, we need to have about one billion stem cells because efficacy to transform them into insulin-producing cells varies between 15% and 40%. I don’t believe that we will be able to solve the problem of brittle diabetes with transplantation of stem cell-derived islets (alpha and beta cells mixed into 3D organoids) alone,” he stated. “We should remember the lesson learned from pancreatic islet transplantation, whether we use original islets derived from a donor pancreas or produced from a patients’ stem cells, it will not solve the problem. In my opinion, we have to give those new islets a special nest, which involves an extracellular matrix through our bioinks and vessels with oxygen supply.”

Researchers at Polbionica have recently performed studies on mice proving that the bioprinted pancreatic petals using bioinks were well tolerated by the animals without any extended foreign body reaction to them. In April they will move onto studies with pigs and are planning studies with bigger animals together with Artur Kaminski, head of the Department of Transplantology and Central Tissue Bank at Warsaw Medical University.

“We expect clinical trials will be performed in Warsaw with the cooperation of our partners MediSpace Medical Centre and Warsaw Medical University. However, to begin this stage, we still have to overcome a few hurdles, like product stability, animal trials, approval from authorities as well as funding. If all that happens, just a few patients will be involved in the first stage of the clinical trial, mainly those who cannot receive any other treatment, and we have to remember that for the majority of people with diabetes, intensive insulin intake with CGM control is sufficient,” described Wszoła.

In 2012, diabetes expenses around the world accounted for 11% of the total health care expenditure. The Polish state needs close to one billion euros every year for diabetes. According to Wszoła, their potential competition, working on developing artificial pancreas is only offering a bridge treatment. Polbionica wants to go beyond that: their bionic pancreas could be a living organ that is a breakthrough in the treatment of type 1 diabetes.

He, along with his team hopes that their final product and know-how will solve problems related to the shortage of organs, postoperative complications and immunosuppression after transplantation, and above all, will be a chance to completely cure type 1 diabetes.

Moreover, the positive development of the organ production technology would significantly affect the general health of society, largely eliminating the problem of diseases associated with end-stage organ failure, reducing treatment costs, the need for social care, and professional absenteeism, while improving the quality of life of patients, and speeding up the process of introducing new drugs into the market.

“Bioprinting can have a great impact on the development of medicine, however, like every technology, it also has some limitations. We must remember that we are handling living cells, and the stress and other conditions which cells undergo during the bioprinting process has an influence on its function. Besides, we still have to work on better materials to build organs, materials that will keep cells together and allow them to function properly, materials with special strength, viscosity, and elascity,” claimed Wszoła.

The technology established by Polbionica even could let researchers bioprint vascularized organ models with cancer tumors to conduct research on the efficacy of newly implemented drugs. It may even revolutionize drug implementation routes and help diminish the need to perform animal studies.

“The field of drug testing can highly benefit from bioprinitng, with our technology we are now able to bioprint different pathologic models, such as pancreatic and liver cancers, melanomas, large bowel and breast cancer. We can also mimic microenvironments within tumors, print vessels and observe them in the lab when we add drugs and perform different analysis. In short, we can give a lot of answers and have an insight on drug development like never before.”

Polbionica is implementing the project as part of the Prevention Practises and Treatment of Civilization Diseases (STRATEGMED) program, funded by the Polish National Center for Research and Development. With experts in the fields of biotechnology, chemistry, mechatronics, bioprinting, and medicine, the team is moving forward quite rapidly in an area that to date has no cure, new technology can help patients reduce the burden of managing the condition, especially with regards to measuring their blood sugar levels and administering insulin, however, breakthroughs are not common. And although still in animal trials, the team is looking forward to the day when they will bioprint a bionic pancreas with living cells and tissues using their own bioinks.

The post Polbionica Could Become the Next Success Story in Organ Bioprinting 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.

The post CELLINK in France: Expanding Their Portfolio in 2020 appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

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High-definition 3D printed organ models? German scientists think the answer is clear

Scientists at Ludwig Maximilians University in Munich have developed a new technique to make organs, and even whole organisms transparent – which aims to lead to high-fiedlity 3D printed models. The research team led by Dr. Ali Ertuerk developed the new technique, referred to as vDISCO, which uses a solvent to make living organs such […]

CELLINK and Volumetric introduce Lumen X 3D bioprinter for larger vascular structures – Technical specifications

CELLINK, the Swedish manufacturer of the BIO X 3D printer, and Volumetric a Texas-based biomaterials and biomanufacturing company, have introduced the Lumen X Digital Light Processing (DLP) bioprinter to produce large vascular structures. Designed as an entry-level platform, the Lumen X works with patent-pending bioinks to print high-resolution, macroporous, and vasculature structures, strengthening research regenerative medicine. […]