3D bioprinting of a bionic pancreas with a vascular system - results of transplantation in large animals.
Michał Wszoła1,2,3, Andrzej Berman1,2,3, Marta Klak1,2, Tomasz Dobrzański1, Oliwia Janowska1, Dominika Ujazdowska2, Dominika Szkopek4, Katarzyna Roszkowicz-Ostrowska4, Agata Kondej4, Jarosław Woliński4, Artur Kamiński5, Agnieszka Dobrzyń6.
1Polbionica Inc., Delaware, DE, United States; 2Foundation of Research and Science Development, Warsaw, Poland; 3Medispace Medical Centre, Warsaw, Poland; 4The Kielanowski Institute of Animal Physiology and Nutrition PAS, Jablonna, Poland; 5Warsaw Medical University, Warsaw, Poland; 6Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
Purpose: 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 or knocked-out xeno-derived islets, with use of dECM-derived biomaterials with stable flow through the organ in vitro and in large animal studies.
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 bloodvessels formation).
Conclusions: It is feasible to 3Dbioprint and transplant bionic organ in big animal model as a macro-device for stem-cell derived beta cells or knocked-out xeno-derived islets.
