Pancreas 3d printing


3D Bioprinting for Artificial Pancreas Organ

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. 2018;1064:355-374.

doi: 10.1007/978-981-13-0445-3_21.

Seon Jae Lee  1 , Jae Bin Lee  1 , Young-Woo Park  1 , Dong Yun Lee  2   3

Affiliations

Affiliations

  • 1 Department of Bioengineering, College of Engineering, BK21 PLUS Future Biopharmaceutical Human Resource Training and Research Team, Hanyang University, Seoul, South Korea.
  • 2 Department of Bioengineering, College of Engineering, BK21 PLUS Future Biopharmaceutical Human Resource Training and Research Team, Hanyang University, Seoul, South Korea. [email protected]
  • 3 Institute of Nano Science & Technology (INST), Hanyang University, Seoul, South Korea. [email protected]
  • PMID: 30471043
  • DOI: 10.1007/978-981-13-0445-3_21

Review

Seon Jae Lee et al. Adv Exp Med Biol. 2018.

. 2018;1064:355-374.

doi: 10.1007/978-981-13-0445-3_21.

Authors

Seon Jae Lee  1 , Jae Bin Lee  1 , Young-Woo Park  1 , Dong Yun Lee  2   3

Affiliations

  • 1 Department of Bioengineering, College of Engineering, BK21 PLUS Future Biopharmaceutical Human Resource Training and Research Team, Hanyang University, Seoul, South Korea.
  • 2 Department of Bioengineering, College of Engineering, BK21 PLUS Future Biopharmaceutical Human Resource Training and Research Team, Hanyang University, Seoul, South Korea. [email protected]
  • 3 Institute of Nano Science & Technology (INST), Hanyang University, Seoul, South Korea. [email protected]
  • PMID: 30471043
  • DOI: 10.1007/978-981-13-0445-3_21

Abstract

Type 1 diabetes mellitus (T1DM) results from an autoimmune destruction of insulin-producing beta cells in the islet of the endocrine pancreas. Although islet transplantation has been regarded as an ideal strategy for T1D, transplanted islets are rejected from host immune system. To immunologically protect them, islet encapsulation technology with biocompatible materials is emerged as an immuno-barrier. However, this technology has been limited for clinical trial such as hypoxia in the central core of islet bead, impurity of islet bead and retrievability from the body. Recently, 3D bioprinting has been emerged as an alternative approach to make the artificial pancreas. It can be used to position live cells in a desired location with real scale of human organ. Furthermore, constructing a vascularization of the artificial pancreas is actualized with 3D bioprinting. Therefore, it is possible to create real pancreas-mimic artificial organ for clinical application. In conclusion, 3D bioprinting can become a new leader in the development of the artificial pancreas to overcome the existed islet.

Keywords: 3D bioprinting; Artificial pancreas; Hypoxia; Islet transplantation; Scale up; Type 1 diabetes.

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Readily3D develops 3D bioprinted mini pancreas for diabetes drug testing

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Volumetric 3D bioprinter manufacturer and EPFL spin-out Readily3D has taken the first step towards developing a 3D printed living model of the human pancreas for testing diabetes medicines.  

Readily3D’s novel technology is being deployed within the EU-funded Enlight project and is reportedly capable of 3D printing a biological tissue containing human stem cells in just 30 seconds. 

As the project’s official bioprinter manufacturer, the company has adapted its proprietary contactless tomographic illumination technology to suit the specific needs of pancreatic tissue structures.

“Developing a system that can 3D print tissue at the cubic centimeter scale and faithfully replicate the functioning of a live pancreas is a huge challenge, which we hope to meet with this technology,” said Christophe Moser, Head of the EPFL’s Laboratory of Applied Photonics Devices (LAPD). 

The mini 3D bioprinted pancreas. Image via EPFL / A. Herzog.

Combating pancreatic disease and diabetes

Located just behind the stomach, the pancreas serves several vital functions, such as producing enzymes and bicarbonates essential for digestion and secreting a variety of hormones. One of these hormones is insulin, which regulates the body’s blood sugar levels. As such, pancreatic disease can often lead to the development of diabetes as the organ’s damaged cells can no longer produce the insulin the body needs. 

According to The International Diabetes Federation and the European Diabetes Study Center (CeeD), more than 450 million adults worldwide suffer from diabetes, and this number is continuing to grow. Diabetes is also reportedly the second-leading cause of amputation and significantly increases the risk of a heart attack, stroke, and kidney failure.

The Enlight Project has received €3.6 million in funding from the EU’s Horizon 2020 Framework Program to develop the first living model of the pancreas within the next three years. The project is being carried out by a consortium led by UMC Utrecht and made up of EPFL, ETH Zurich, the University of Naples Federico II, AstraZeneca, Rousselot, Readily3D, and the Giannino Bassetti Foundation.

The overarching aim of the Enlight project is to develop the living pancreas model for the testing of new diabetes medications to improve both diagnosis and treatment of the condition.  

Readily3D’s Tomolite 3D bioprinter. Photo via Readily3D.

3D printing the pancreas

The novel bioprinting technology is based on Readily3D’s existing Tomolite 3D printer, which uses a biological gel containing a patient’s stem cells. A laser is then applied to the gel to solidify it via polymerization, with the location and intensity of the laser beam controlled to solidify only those areas of the gel needed to form the desired tissue. 

“One of the main advantages of our method is that it can create tissue in a single block, making it particularly useful for printing soft tissue like organs,” said Paul Delrot, CTO of Readily3D. 

The bioprinter is reportedly capable of printing the centimeter-scale structure in less than 30 seconds, a significant achievement as the survival rate of living cells decreases drastically as print times increase. 

Readily3D’s technology was selected for use within the Enlight Project earlier this year. The technology enables tailor-made structures to be printed as it is created from a patient’s own stem cells, meaning patients will no longer have to try out an array of drugs, some of which can have unpleasant side effects, before finding the right one for them.  

According to the consortium, the technology developed during the project could be used to bioprint other kinds of tissue for developing treatments for cancer, or even for producing transplant organs, in the future.

The technology additionally eliminates the need for animal testing, a goal that is also sought by researchers at the University of Stuttgart and Robert Bosch Hospital who have announced the development of a novel 3D printed tissue platform that could replace animal testing within clinical trials of cancer drugs. 

In a similar vein, 3D bioprinter manufacturer CELLINK recently acquired in-vitro technology specialist MatTek Corporation to advance its research into animal cruelty-free cellular testing models.

Further work addressing new methods of drug testing for diabetes has been carried out by a team from Pohang University of Science and Technology and Pusan National University. The team 3D printed an in vitro artificial skin model to observe skin diseases suffered by diabetic patients to which test drugs can be applied.

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Featured image shows the mini 3D bioprinted pancreas. Image via EPFL / A. Herzog.

Tags AstraZeneca CELLINK Christophe Moser Enlight project EPFL ETH Zurich European Diabetes Study Center Giannino Bassetti Foundation Paul Delrot Pohang University of Science and Technology Pusan National University Readily3D Robert Bosch Hospital Rousselot The International Diabetes Federation The MatTek Corporation UMC Utrecht University of Naples Federico II University of Stuttgart

Hayley Everett

Hayley is a Technology Journalist for 3DPI and has a background in B2B publications spanning manufacturing, tools and cycling. Writing news and features, she holds a keen interest in emerging technologies which are impacting the world we live in.

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    First 3D-printed bionic pancreas with blood vessels

    The world's first bionic pancreas with blood vessels was printed by Polish scientists from the Foundation for Research and Science Development, led by Dr. Michal Wszola. In April, the scientists plan to implant pancreatic lobes and islets into mice to test their function in vivo. Experiments on pigs are scheduled for October 2019of the year. “No one has grown a fully vascularized parenchymal organ before,” said transplant surgeon Dr. Michal Wszola. Previously, he developed a new method of minimally invasive treatment of complicated diabetes using endoscopic transplantation of pancreatic islets under the gastric mucosa. His new project, a bionic pancreas, could also treat diabetes in the future.

    Michal Vszola, surgeon, expert in transplantation

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    Printed pancreas composed entirely of pancreatic islets; it lacks exocrine function. Researchers believe that it will be able to restore the production of insulin in the body of a diabetic. Currently, this is only possible by administering the hormone using an insulin dispenser or pump.

    “The human pancreas produces pancreatic juice that helps us digest food. It also carries about a million pancreatic islets, small projections made up of alpha and beta cells that produce insulin and glucagon. People with diabetes have damaged pancreatic islets and lack the cells that produce insulin and glucagon. Only pancreatic juice is produced. So they use insulin injections. We decided to grow an organ that would produce insulin and glucagon using alpha and beta cells,” Dr. Wshola told PAP.

    Polish scientists took islet cells from animals and mixed them with bio-ink, a substance that allows the cells to survive. The bioprinter began to place them in the bioreactor in accordance with the previously developed three-dimensional scheme. At the same time, using a second syringe, the researchers printed the blood vessels through which blood would flow in the organ.

    “After printing our pancreas, we didn't look at how natural it looked, we weren't interested at all. We confirmed that we were able to print an organ 1-1.5 cm thick, and that this organ has a dense vasculature so that all pancreatic islet cells are well supplied with glucose and oxygen,” says Dr. Wshola.

    Polish engineers needed to create the right bioink because none of the existing inks were suitable for this experiment. Another difficulty was to ensure that the liquid in the syringe, in the cartridge - after printing and exposure to physical and chemical factors - becomes dense and forms layers, and also retains its structure.

    “A mathematical study allowed us to estimate how functional this organ will be after activation of the blood flow. How blood will behave in this organ depending on the different values ​​of its pressure and hematocrit - the number of red blood cells in the blood. Some vessels needed to be lengthened, others shortened,” says Dr. Vshola.

    Scientists at work

    In April pancreatic lobes with islets will be tested in mice. These tests will end in June. In October 2019, a large fragment of the pancreas several centimeters in size with vessels will be tested on pigs.

    “We need to check how the organ will function in a living organism, how microcirculation will form in it and how its structure will change,” says Dr. Wshola. According to the doctor, no one has done this before. “In other experiments, biodegradable scaffolds are populated with cells and then implanted in humans. This can only be used for certain tissue types such as cartilage, bone, trachea, or bladder, but not for the liver, pancreas, kidneys, or lungs, because these are parenchymal organs that need a vasculature. Vascularization was a big problem,” he says.

    “We will present the results of our work on the bionic pancreas during the charity auction of scientific papers on March 14 and look forward to reaching out to businesses for further development,” says Dr. Wszola. He explains that this particular bionic pancreas was printed from porcine cells: "But that's not important, because we're using it as an example."

    The Bionic Pancreas 3D Printing Project by the Foundation for Research and Science Development is co-funded by the National Center for Research and Development under the STRATEGMED III program. The members of the consortium are Nencki Institute, Warsaw University of Technology, Medical University of Warsaw, Infant Jesus Hospital and MediSpace.


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