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.

Caterpillar Is a Powerful Rhino Grasshopper Plug-in for Greater Customization in 3D Printing

Bio-inspired 3D printings by (Zheng and Schleicher 2018)

Whether you are a serious 3D printing user or not, you have probably heard of Grasshopper, a popular add on of 3D modeling software Rhino. Grasshopper lets you use scripts and algorithms to create 3D models and generative designs. It is one of the quickest ways through which designers can get started with generative designs and lets you in a visual build things such as parametric designs or designs based on datasets. You may not yet be familiar with other features, however, recently outlined by University of Pennsylvania’s Hao Zheng in ‘Caterpillar – A GCode Translator in Grasshopper.’ Here, we learn more about a new plug-in Caterpillar and its ability to unleash full use of the three degrees of freedom of Computer Numerically Controlled (CNC) machines and non-traditional 3D printing. Caterpillar lets you generate Gcode from within Grasshopper. Your dataset or generative algorithm or existing model can now be quickly turned into Gcode that you can then optimize for 3D printing. This will enable people to quickly implement very creative and new 3D printing methods and techniques as well as enable the making of more non-traditional 3D printing processes.

Zheng points out what many of have noticed over time, as 3D printing users are simply not satisfied to stop and enjoy what has been supplied to them in terms of what is now traditional 3D printing in the layer-by-layer, bottom-to-top approach. For better control, Zheng postulates that users must be able to use ‘the three degrees of freedom’ – meaning X, Y, and Z and also go beyond them. More degrees of freedom and different ways of printing mean more applications are possible. The developers have added to conventional methods previously with accompaniments such as robotic arms, 3D printers that print on curved surfaces, as well as those that extrude alternative materials like wire.

For Caterpillar to do the necessary work, you must first give it the necessary data required. This means printers settings, to include many different parameters:

“Printer bed size (MM) contains three numbers (x, y, z), indicating the maximum printing size of the printer. Heated bed temperature (°C), extruder temperature (°C), and filament diameter (MM) are based on the printing material, which normally will not be changed once settled. Layer height (MM) and subdivision distance (MM) control the precision of the printing, while printing speed (%), moving speed (%), retraction speed (%), and retraction distance (MM) control how fast the printer will act when printing, moving without printing, and retracting materials. Extruder width (%) and extruder multiplier (%) together decide the width of the printed toolpaths.”

Work flow of Caterpillar in Grasshopper

Most users can just go with their default settings to be safe, but there may be some cases where you want to customize without default restriction. Infill settings must be considered too if you are slicing the model to provide infill.

For slicer and toolpath generation, there are numerous options:

  • Planar slicer
  • Curved slicer
  • Curved toolpaths for special use
  • User-defined toolpaths

Planar Slicer (left), Curved Slicer (middle), User-defined Toolpath (right)

The workflow of the GCode generator then creates toolpaths based on points based on inputted curves, and optimization occurs:

“So before inputting the given curves to the dividing component, the program will detect and separate curved toolpaths and linear toolpaths, then divide the curved toolpaths as usual and extract the start and end points to represent the linear toolpaths.”

The GCode decoder then translates text files, assisting users in further design and control through keywords extraction and model rebuilding.

Commonly-Used Gcode.

“In the future, non-conventional customized 3D printing will be highly developed for both educational and industrial purposes,” concludes Zheng. “Low-cost 3-axis 3D printers with extra toolkits can handle a variety of tasks, providing an alternative for expensive robotic fabrication.”

In 3D printing, the central theme is customization. Users can create on an infinite scale, whenever they want, rapidly and affordability. Hardware choices continue to expand with the needs of 3D printing enthusiasts around the world, as do materials. Changes and evolution in software tend to be even more sweeping—and desired—as computer programs allow us to design objects and then control printing processes. While add-ons, plug-ins, and updates are continually available, software programs drive innovations—whether in allowing more advanced bioprinting and tissue engineering, scanning, or simulation of other processes. Caterpillar makes is much easier to implement, design and develop completely new 3D printing techniques and we can not wait to see the impact that this will have.

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Printing Simulation

[Source / Images: ‘Caterpillar – A GCode Translator in Grasshopper]

Is Higher Extrusion Speed Key to Improving FDM Part Quality?

FDM 3D printing technology is being used for more and more high-performance industrial and scientific applications as materials evolve, and filaments made from PEEK, PEKK and other high-temperature materials become more accessible. However, FDM 3D printing has its flaws, like porosity and poor adhesion, which results in unsatisfactory sealing properties. Effective sealing of gases and liquids is necessary for items used in research, industry and other applications. In a paper entitled “Improvement of quality of 3D printed objects by elimination of microscopic structural defects in fused deposition modeling,” a group of researchers discuss easy ways to assess and improve the quality of 3D printed objects.

For their experiment, the researchers used a variety of materials to 3D print several basic shapes: a cylinder, a cone, a sphere, a joined cylinder and cone, a pyramid, and a cube, using a Picaso 250 Designer Pro 3D printer. To evaluate the quality of the 3D printed objects, they developed a special system. The 3D printed objects were connected to an air compressor by a flexible pipe and placed in a transparent glass container filled with water.

“A slight internal gas pressure applied through the pipe induced outgassing in the form of bubbles emanating from the intrinsic pores, which permeated the wall of the product,” the researchers explain. “The intensities and densities of the bubble flows corresponded to the linear dimensions and densities of the pores, respectively. The larger the diameter of the pore, the more intense the formation of air bubbles through this pore. The quantitative density of air bubbles on the surface of the printed part corresponds to the density of the through channels inside the wall. This experiment provided both visualization and quantitative assessment of the 3D printing quality. Importantly, the described approach was applicable to the objects independently of their shape.”

The researchers varied several parameters while 3D printing the objects, and found that the porosity depended most strongly on the extrusion multiplier.

“Extrusion multiplier is the parameter for controlling extrusion flow rate, i.e. the volume of melted plastic material extruded through the nozzle per unit time,” they continue. “Technically an increase in the extrusion multiplier usually leads to an increase in the speed of rotation of the gears in the feeding mechanism of the printed head.”

The lower the extrusion multiplier, the higher the porosity of the objects, they discovered. They describe the extrusion multiplier as a k-value, and at k=0.98 the objects became completely sealed and impermeable. This was true no matter what material was used; the varying materials included PLA, ABS, nylon, carbon fiber-reinforced nylon, PETG and PP. The researchers then repeated the experiment using a Designer X Pro 3D printer, and found that the k-values varied slightly due to differing extruders.

The porosity of the objects also depended on their shapes. Under standard conditions, the cylinder was the least porous and the conical objects had the largest pores evenly distributed over their surface. With the hexagonal pyramid and the cube, the pores were most prevalent at the edges. The experiments showed that edges and vertices are most prone to defects.

Another set of experiments showed that wall thickness and altered G-code can have an effect on permeability, as well.

“…to minimize the porosity, the proper filling of the inner space should be additionally controlled by verification of the G-code suggested by the slicer software,” the researchers state. “The more homogeneous the intermediate layer of the wall is, the more impermeable the wall of the product will be, since all the seams will be securely insulated from each other.”

They concluded from the experiments that wall thickness should allow for an internal diagonal filling, that the seams for each layer should be distributed in random positions, and that cylindrical objects are the easiest to make impermeable. Overall, with the proper manipulation of parameters, desktop 3D printers can be used to create impermeable objects, suitable for lab equipment and other applications.

Authors of the paper include Evgeniy G. Gordeev, Alexey S. Galushko, and Valentine P. Ananikov.

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