Whenever the futuristic visions of the past are closer to becoming a reality we wonder what the next step for humanity will be. But when it comes to medicine, every step is a long one, pre-clinical and clinical trials take years, and if we look at some of the known facts, the discipline has advanced but it hasn’t changed very much. For example, it’s been 50 years since the first successful heart transplant, and human donors are still required today. Heart transplants are still risky and complex procedures now so many years later. Artificial organs are the next step beyond this. With the help of 3D bioprinting technology more and more researchers are creating functional organoids but we still seem far away from implanting organs. We keep hearing from experts that additive manufacturing has advanced so many industries and sciences, but not medicine, or at least not as much we expected it would. But every once in a while, we hear stories about doctors attempting to ride the wave of the impossible, and that is what Michal Wszola has been doing for the last ten years. The general surgeon and transplantologist’s closeness to patients throughout his career has driven him to search for solutions to diabetes, chronic pancreatitis and kidney disease, some of the most common illnesses he treats every day. The Polish-born specialist and creator of the first bionic pancreas with microvasculature spoke to 3DPrint.com about the future of his venture as well as the need to use bioprinting to advance into the next chapter of the medical revolution.
In 2009 Wszola established the Foundation of Research and Science Development in Warsaw, Poland, to enhance educational and research activities in the field of medical and biomedical sciences. Wszola has been actively searching for groundbreaking medical therapies to help patients with diabetes and secondary problems, as well as patients that are referred to the transplantation wards for either pancreas or islet transplantation. The current focus of the Foundation is on a 3D bioprinting project for a bionic pancreas, an organ that could enable people with diabetes to attain normal functions and will also replace the need for chronic insulin therapy. His team also developed two bioinks to be used with pancreatic islets, which will be commercially available soon.
The project involves bioprinting of 3D scaffolds along with functional vessels and pancreatic islets and as a result, the forming of a fully functional bionic pancreas that would be suitable for transplantation.
“Last March, we bioprinted the bionic pancreas for the first time using islet cells from mice and another from pigs, creating an organ that is one third the size of a regular pancreas; but in this case, the size is not important since we just want the function of the islets, responsible for the production of insulin. What my team and I are interested in, is to have a pancreas ready to cure diabetes, not to repair the native organ. In the organ we bioprinted, we can place one million pancreatic islets, which is already sufficient to cure diabetes.”
The bionic pancreas project aims to create a customized pancreas from the patient’s own stem cells, which would eliminate any risk of rejection. Stem cells will then be transformed towards cells producing insulin and glucagon and bioprinted; finally, the bionic pancreas would be tested for functionality prior to the human transplant. Organs like the liver, pancreas or kidneys are complex to reproduce since they require a vascular system, and in this case, vascularization was a major challenge for Wszola and his team. The bioprinted organ needed to have a dense vascular network so that all pancreatic islet cells would be well supplied with glucose and oxygen. At the Foundation lab, Wszola and his team use CELLINK bioprinters to conduct their experiments.
The animal studies with mice are a first attempt to observe how bioprinted microvasculature can ingrow into the new pancreas. The key is to analyze how long this process will take and once he has that number (which could be anything from days to weeks or even months), he will publish a paper along with colleagues from the Foundation and a consortium, which includes the Medical University of Warsaw, Warsaw University of Technology, Nencki Institute of Experimental Biology, Medispace and Infant Jesus Hospital.
Poland already has a strong medical background in pancreatic research. Back in 1965, Stanislaw Moskalewski was able to, for the first time, successfully isolate islets from the pancreas of minced guinea pigs. Of course, more investigations followed with later experimentations in the United States leading to islet transplantation from donor pancreas, however, Wszola believes that this method has two main problems: lack of vasculature and complex islet isolation–which removes the extracellular matrix from the islets. So he began leading a team in 2013 to learn how bioprinting can help them figure out how to develop islets with vasculature already incorporated.
“I decided that bioprinting could solve the islet vasculature problem so I began searching for ways to use it in medicine and soon learned that what I wanted to print was an organ with viable islets, endothelial cells, and vessels. At the Foundation, we use pressure control bioprinting and study the maximum pressure needed for bioprinting each kind of cell.”
Another part of the study was dedicated to establishing a special bioink, since Wszola claims that the bioinks they could commercially buy were not suitable for the clinical transplantation. All bioinks were isolating the islets from the outer environment, which makes the transfer of insulin from pancreatic islets and oxygen into the islet cells difficult, so basically letting them die. Along with colleagues, he created bioinks and Polbionica, a startup, to sell them once they become commercially available. One of the bioinks imitates the extracellular matrix of the islets and has permeability so that it is similar to what we find in natural tissue; the second bioink enables scientists to bioprint vessels around the islets and both are used to create the bionic pancreas by Wszola and his team.
Wszola went on to explain that he is “a transplant surgeon so my objective is to move on to human clinical trials. When we finish the current study with mice, we will move to bigger animal models, which will take between one and two years. After the results from the preclinical trials are analized we could be ready to begin the clinical trials. If everything moves as planned, we expect to be transplanting bioprinted bionic pancreas in three to five years.”
Much of the work also involves lab work to transform stem cells into insulin. Wszola claims he prefers to use stem cells than pancreatic cells, but this technique is still in its infancy and could take some years to develop. He believes that the first step is to “start transplantation with the islets and get some positive feedback, however, stem cells will work better than islet transplantation because it could help a larger group of patients.”
[Images: Michal Wszola and the Foundation of Research and Science Development]
“I personally know too many people facing life threatening conditions due to pancreatic disease, I see the patients that need help every day, and above all, I need to tell them something that will give them hope for the future. This is what drives my personal mission, the thousands of humans behind the disease help me work very hard to carry out research and fulfill the possibility to start clinical trials. I believe my work will be finished when I see my patients walking out of the hospital, confident that they have survived and don’t have diabetes,” concluded the expert.
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