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-16 3D bioprinting of a bionic pancreas with a vascular system as a macro-device for stem-cell derived beta cells – results of transplantation in large animals

Michal Wszola, Poland

prof.
Polbionica Sp. z o.o.
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Biography

A transplant surgeon, dedicated physician and visionary scientist, and CEO of Polbionica Inc. Originator of the bionic pancreas – an organ that will restore the body’s ability to regulate blood sugar and revolutionize the treatment of diabetes. He has been running a medical practice for years, leading a team that conducts innovative research - on a global scale – and searches for innovative solutions in medicine. He participated in the first pancreatic islet transplant in Poland (2008), the first pancreas-only transplant (2010) and the first exchange of kidney pairs between family donors (2015). The combination of his passions, transplantology and endoscopy, led to the creation of a new method of treating diabetes – endoscopic transplantation of pancreatic islets under the gastric mucosa. In 2013, he performed first such procedure in the world, which is now tested in several centers in the United States of America. He is currently continuing to work on a 3D printing project of a bionic pancreas with a research team at the Foundation of Research and Science Development. Since 2017, the Foundation, as the leader of the Bionic Consortium, has been working on the implementation of the bionic pancreas project. After only 2 years of preparation and testing, we printed the world’s first vascularized bionic pancreas prototype measuring 3x3x5cm. The 14th of March 2019 is the day when the team proved themselves and the world that the impossible became possible and that tissue and organ bioprinting is the future of modern medicine that will change the lives of many patients. Our mission is to bring 3D printing of the bionic pancreas into clinical practice worldwide. Nowadays a broad spectrum of scientific data showing results of transplantation into large animals of 3D bioprinted bionic pancreas are being presented.

Abstract

3D bioprinting of a bionic pancreas with a vascular system as a macro-device for stem-cell derived beta cells – results of transplantation in large animals

Michal Wszola1,2,3, Andrzej Berman1,2,3, Marta Klak1,2, Tomasz Dobrzanski1, Oliwia Janowska1, Dominika Ujazdowska2, Dominika Szkopek4, Katarzyna Roszkowicz-Ostrowska4, Agata Kondej4, Jarosław Woliński4, Artur Kamiński5, Agnieszka Dobrzyń 6.

1Polbionica Sp. z o.o., Warsaw, Poland; 2Foundation of Research and Science Development, Warsaw, Poland; 3Medispace Sp. z o.o., Warsaw, Poland; 4Institute of Animal Physiology and Nutrition Jan Kielanowski of the Polish Academy of Sciences, Warsaw, Poland; 5Medical University of Warsaw, Warsaw, Poland; 6Institute of Experimental Biology M. Nencki PAN, Warsaw, Poland

The transplantation of the pancreas is recommended in diabetes with complications. The combination of cell biology and 3D-bioprinting can create organs with vasculature which should be functional. dECM derived biomaterials shoved superior functionality when bioprinted with pancreatic islets. In fully vascular organ or macro-device, there are issues to be solved:  leakage, thrombosis, enhancement against high pressure, connecting organ to the recipient. The purpose of this study was to demonstrate 3D-bioprinting of bionic pancreas as a macro-device for stem-cell derived beta cells, with use of dECM-derived biomaterials with stable flow through the organ in vitro and in large animal studies.

Materials and methods: Mathematical analysis in the designed bionic pancreas was performed. The bionic pancreas was 3D bioprinted with 2 types of bioinks. The first tests were carried out in a bioreactor then organs were subjected to magnetic resonance and X-ray with contrast. Pressure endurance tests were performed. 14 pigs received 3D-bioprinted bionic pancreas transplantation. DCL-VESS-Group (n=5) received decellularized vessels as anastomosis. 9 pigs received bionic pancreas with vascular prosthesis as anastomosis - Prosthesis-Group. Pigs were observed up to 14 days. Hist-pat analysis of removed pancreas was performed.

Results: The tests carried out in the bioreactor showed the stability of the bionic organ and vascular system in MRI and X-ray examination for 5 days. No leaks beyond the bionic pancreas were observed up to 400 mmHg. Animals transplantation: In all 14 cases of transplantation there was stable flow throughout the organ after release of vascular clamp. DCL-VESS-Group - In all cases vascular cloth was observed. Prosthesis-Group - In 5 cases there were no complications influencing blood flow through the organ. 4 died to postoperative complications. Stable flow within a transplanted bionic organ was observed till 2 weeks post – surgery within ultrasound examination and radiology intervention in three animals. Histopatological showed the presence of CD31 / PECAM-1 (new blood vessels formation).

Conclusion: It is feasible to 3Dbioprint and transplant bionic organ in big animal model as a macro-device for stem-cell derived beta cells.


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