Posted on

Sciperio Partnering with Multiple Research Companies to Make Human Blood On Demand for Military

Funded by the US Defense Health Program, 4-Dimensional Bioprinting, Biofabrication, and Biomanufacturing (4D Bio3) is a collaboration between the Uniformed Services University of the Health Sciences (USUHS) and The Geneva Foundation, a nonprofit that advances military medical research. The program promotes the application and development of biofabrication, biomanufacturing, and bioprinting technologies for research according to priorities by the US Department of Defense. 4D Bio3 is involved with medical research in outer space, and also much closer to home.

4D Bio3 is currently working with the foundation, Safi Biosolutions, Advanced Bioprocess Services, Massachusetts General Hospital, and Sciperio – the research arm of Florida 3D printing company nScrypt – to make human blood on demand. Yes, you read that correctly.

Through USUHS, the DoD and The Geneva Foundation set up the 4D Bio3 On-Demand Blood Program in order to provide access to fresh, non-contaminated blood supplies for military service members all over the world. The goal of this current partnership with Sciperio is to create solutions for future blood supply, and on-demand manufacturing of human blood seems to be the best way.

Together with Safi Biosolutions, the company received a joint award of $8.8 million to fund any contributions they make to the program in its first year. The overall goal for the program’s inaugural year is to create a “whole blood development roadmap,” and Sciperio’s part will be to develop a rugged, automated bioreactor that offers control and feedback in real-time thanks to multiple sensors. Sciperio spinoff nScrypt, which designs and manufactures highly precise, next-generation, award-winning microdispensing and 3D printing for industrial applications, will be building the bioreactor.

“How do you manufacture blood at a scale relevant for patient use?  We are using several nScrypt SmartPump tool heads to precisely microdispense growth enhancers in the bioreactor, causing cell expansion and differentiation. The bioreactor makes it scalable,” explained Dr. Ken Church, the CEO of both Sciperio and nScrypt. “There are so many interesting aspects and advantages of biomanufacturing blood, including the ultimate benefit to humanity. Starting with a few cells, our bioreactor will produce billions of cells, a necessary requirement for patient transfusion. We believe this exciting project will one day result in a steady source of safe and affordable on-demand blood made where and when it’s needed.”

The nScrypt SmartPump microdispensing tool head works with over 10,000 commercially available materials – the widest range of any microdispensing system. The SmartPump “eliminates drooling with pico-liter volumetric control,” according to nScrypt, and at just 10 microns, its pen tip has the smallest available diameter on the commercial market.

If this project succeeds, and the team is able to additively manufacture human red blood cells on-site that are safe for human transfusion, there will be less need for concern relating to donor blood screening. The solution could mean that extensive donor networks are not as necessary, which can help streamline logistics in terms of blood transportation, processing, and long-term storage. This would be especially helpful for members of the military stationed in remote areas who can’t easily access these services.

Discuss this story and other 3D printing topics at 3DPrintBoard.com or share your thoughts in the Facebook comments below.

(Images provided by nScrypt)

The post Sciperio Partnering with Multiple Research Companies to Make Human Blood On Demand for Military appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

Posted on

Regemat3D Launches its New Bioreactors for Maturing Tissues

One of Spain’s leading biotech companies, Regemat3D, has been developing custom biofabrication systems and regenerative medicine solutions since 2011 to fulfill unique research requirements and offer customized solutions for patients’ needs. Now, the Granada-based startup has launched a new service to produce bioreactors for maturing tissues.

The bioreactors are called Bmap’s, which is short for bioreactors that mimic anatomy and physiology, and are expected to satisfy the demand of a large number of users that require them for growing organisms under controlled conditions. In fact, the demand for these devices has grown significantly in the past years, and Regemat3D plans to develop these mechanobiology devices to create functional tissues for the dynamic 3D culture that uses bioprinting methods, offering a favorable environment for increased growth and proliferation of cell cultures and extracellular matrix (ECM) production.

José Baena, Spanish entrepreneur and founder of Regemat3D said of the new initiative: “The potential of bioprinting is immense, but the industry is missing one part of the procedure, the maturation. A 3D printed scaffold with cells is not a tissue, we need a maturation procedure in a bioreactor in order to promote the tissue formation.”

Regemat3D’s premise has always been to “do not adapt your research to a device.” In fact, the company’s engineers will adapt the device to a customers’ particular research so that they can have better outcomes. The company claims that the selection of the right ingredients or bioinks and bioprinting procedure will be very important in the success of the creation of functional living tissues. However, Baena suggests that “if we think about bioprinting as a technology to recreate all the structures in the same form as shown in living tissue, we are going to fail.” Further highlighting that scientists need to think about bioprinting as a way of creating cell-laden 3D constructs as a precursor to functional tissue, while the maturation and tissue formation process will be as important or even more so than bioprinting.

According to the company, their environment-controlled bioreactors provide optimal nutrients and gases to growing cells and also trigger cellular mechanotransduction signaling pathways to stimulate tissue remodeling onto 3D scaffolding. The systems integrate sensors and actuators to control parameters, such as CO2, pH, humidity, and O2 to apply mechanical signals, like traction, compression, shear stresses, light, and ultrasound.

“The lack of tissue regeneration in human beings, the deficiency of allogeneic transplants and the higher mortality rate of people with organ dysfunction as we see these days with COVID-19, make the creation of functional tissues in the laboratory one of the most important problems for humanity right now,” indicated Baena. “We also need tissue samples that replicate human histology to develop new drugs faster, cheaper and without the use of animal models. However, the results obtained are still less than desired. Even though, the variety of commercial systems now available to researchers has increased, as well as the number of publications, the results obtained are still far from true clinical applications.”

Researchers trying out the bioreactor at the lab (Image: Regemat3D)

Moreover, Baena describes that “a common misconception that the industry has is the belief that we need to directly create functional tissue, but in reality, we are creating a matrix loaded with cells. The key here is to make these cells behave as they do in vivo and to promote the creation of functional tissues, which requires defining the right biofabrication and maturation strategy.”

Thereby, Regemat3D experts believe that in order to create living tissue, both the bioprinting process and the maturation of the construct are crucial. Recreating human adult conditions in the lab or the stimuli that occur during embryogenesis will move the results of tissue engineering closer to clinical applications.

The Bmap bioreactor (Image: Regemat3D)

The entrepreneur also pointed out that real-life experience helps researchers understand that mechanical stress distribution is crucial as a stimulus to create the right tissue. Thereby, he considers the selection of the right ingredients and the bioprinting procedure as a very important part of the success of creating functional tissues, and the maturation procedure applied to the 3D cell-laden constructs even more important.

“This approach will open a wide research area for tissue engineers to develop protocols with different stimuli to create functional tissues, either using direct or indirect bioprinting methods, such as using molds as temporal containers, fiber structure holding loads and a cell-friendly matrix, even adipose tissue containing blood vessels allowing the generation of functional, vascularized and ready to use tissues and organs.”

The new custom device provided by the company will address a broad range of tissue engineering processes and cell culture applications including that of single cells on microcarriers and slow-growing cell types with unsurpassed cell quality. Regemat3D expects their systems will accelerate cell growth, differentiation, and cell proliferation, mimicking native ECM in homogenous cell culture at the surface and core of the 3D scaffolds creating functional new living tissue.

The company also expects it will be used by research institutes, hospitals, biotechnology and pharmaceutical companies in a wide range of applications, such as bone regeneration, biomedical testing, adipose tissue for breast reconstruction, bone marrow stromal cells, cartilage regeneration, heart patch research, co-culture human fetal mesenchymal stem cells (hfMSC) and co-culturing with endothelial progenitor cells (EPC), and even stem cell expansion.

One of Regemat3D’s case studies involves a patented bioreactor, the Bmap Knee, that reproduces the in vivo conditions of the knee to generate functional cartilage, controlling the parameters, like the temperature. While another bioreactor, the Bmap Artery, mimicks in vivo conditions to generate functional arteries in vitro, controlling parameters such as flow and rotation for cell adhesion. Both of them are available via Regemat3D’s online shop, along with other customized bioreactors that the company is fully ready to develop. 

With so much work ahead for researchers in the field of biofabrication and enough pressure surmounting from the public to find novel solutions to common problems and diseases, perhaps devices like Regemat3D’s bioreactors could eventually help improve the lives of millions of people. Baena considers “it’s worth the time and effort.”

The post Regemat3D Launches its New Bioreactors for Maturing Tissues appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

Posted on

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.

Posted on

Researchers Test Two Configurations of Biowaste 3D Printed Microbial Fuel Cells

Researchers and scientists are constantly working to develop solutions that can save our future world, from solving problems like increasing pollution and climate change to producing clean energy. A group of researchers from the University of Naples Parthenope recently published a paper, titled “Development and Performance analysis of Biowaste based Microbial Fuel Cells fabricated employing Additive Manufacturing technologies,” about their efforts to test two different configurations of microbial fuel cells (MFCs): bio-electrochemical devices which can directly produce power by converting stored energy into a substrate. MFCs have this unique capability thanks to electrogenic bacteria that can produce and transfer electrons to an electrode with which they are already in contact.

The abstract reads, “In this work two different configurations of MFCs are tested, evaluating the importance of the operative conditions on power production. All the MFCs were fabricated employing 3D printing technologies and, by using biocompatible materials as for the body as for the electrodes, are analyzed the point of strength and development needed at the state of the art for this particular application. Power productions and stability in terms of energy production are deepen investigated for both the systems in order to quantify how much power can be extracted from the bacteria when a load is fixed for long time.”

Reactor Design.

The three main transfer mechanisms are electron shuttles, conductive nanowires, and redox reactions between bacteria and the electrode. Scaling up for real MFC applications would be expensive, as the needed materials, like NafionR and platinum, are costly. But 3D printing can be used to help lower costs, as well as offer more stable energy production.

“Due to that a more sustainable and less wasteful production can be applied to MFCs bioreactors. In addition, materials suitable for 3D printing are moving to bio-based solutions completely recyclable that would strength the sustainability by closing the loop also for the materials,” the researchers wrote.

For their study, the team investigated and tested two kinds of reactors: single chamber and double chamber. The biggest difference between them regards the use, or lack thereof, of a chamber for locating the cathode electrode.

Exploded and Compact view of (A) Single Chamber MFC, (B) Double Chamber MFC.

“In the reactors design the distances between cathodes and anodes in both layouts is fixed to 2 cm,” the researchers explained.

“In the single chamber configuration, activated carbon coated with PTFE and a nickel mesh as current collector are used as cathode (7 cm2 as active surface area) and a PLA based material is used for realizing the anode (9.7 cm2 active surface area).

“In the double chamber reactor, both electrodes (cathode and anode) are realized by using the PLA based material like that used for the anode of the single chamber reactor. These electrodes have also the same shape (9.7 cm2 active surface area). Moreover, a cation exchange membrane (CEM) is used as medium between the two chambers.”

Open source Free CAD was used to design the cube-shaped reactors, which included an internal circular hole for extra volume, and a Delta Wasp 20 40 3D printer fabricated the reactors out of non-toxic, conductive PLA from Proto-pasta.

The researchers noted, “This material is suitable for the application in MFC, but improvements are needed in order to obtain better power production.”

The team used bacteria from a mixture of compost taken from an Italian waste treatment facility and household vegetable waste for their experiments, and left the 3D printed reactors in a temperature-controlled environment of 20°C for 48 hours before beginning acquisitions.

“An experimental data acquisition system, is used to record the performances of the MFCs, consisting of an embedded system controlled by an Arduino board connected to sensors that recorded voltage and current at each operative condition set. The DAQ, with a sample frequency of 0.1 Hz (10 s), is able to switch automatically the resistance applied at the ends of the electrodes in order to easily obtain polarization curves. In particular, polarization procedure consists in the application of four different resistance (36000-27000-12000-8000 W) for 5 minutes each,” the researchers wrote.

“The procedure is continuous, so the total time needed is 20 minutes. Finally, the value of resistance that gives the maximum power is applied for four hours in order to test how the response of the same to an extended load.”

Conductive PLA Electrode Design.

The researchers continuously recorded the MFCs’ Open Circuit Voltage (OCV), and the double chamber system showed a higher starting potential of 0.95 V compared to the 0.59 V of the single chamber system. They noted a “great stability” during their experimental tests, and determined that 3D printing is “a suitable technology for the fabrication of the MFC in terms of precision and costs.”

“Results of the experiment show that both configurations are affected by a high internal resistance and, as a consequence, a limited power production has been achieved. As expected, better results are registered for the double chamber, mainly due to the use of CEM and the presence of potassium permanganate at the cathode that, probably, better balanced the redox reactions that occurred,” the team concluded. “However, this difference is very low (+11%) and the reason can be found in the materials used for the electrodes. AC coated with PTFE electrode (1 W resistance), used as cathode in the first configuration, allows better performance than the conductive PLA (400 W resistance approximately).”

Co-authors of the paper are Elio Jannelli, Pasquale Di Trolio, Fabio Flagiello, and Mariagiovanna Minutillo.

Discuss this research and other 3D printing topics at 3DPrintBoard.com or share your thoughts below.