Insulin-independence of diabetic pigs after autotransplantation of 3D-bioprinted bionic pancreatic tissue petals
Andrzej Berman1,2,3, Michal Wszola1,2,3, Marta Klak1,2, Oliwia Jankowska1, Dominika Ujazdowska2, Sylwester Domanski1, Tomasz Dobrzanski1, Dominika Szkopek5, Anna Filip2, Katarzyna Roszkowicz-Ostrowska5, Agata Kondej5, Jaroslaw Wolinski5, Artur Kaminski4.
1Polbionica Inc., Delawere, DE, United States; 2Foundation of Research and Science Development, Warsaw, Poland; 3Medispace Medical Center, Warsaw, Poland; 4Warsaw Medical University, Warsaw, Poland; 5Institute of Animal Physiology and Nutrition Jan Kielanowski of Polish Academy of Sciences, Jablonna, Poland
Introduction: The first milestone of a new therapy for the treatment of T1D is the development of 3D bioprinted petals consisting of: pancreatic islets and biomaterials. The aim of the study was to demonstrate the functionality of pancreatic islets in in vivo studies on large animals.
Materials and Methods: Domestic pigs were the research model. The animals were divided into 4 groups:(1)healthy pigs (Control; n=3);(2) animals with T1D after pancreatectomy, treated with insulin (T1D;n=3);(3) animals after pancreatectomy and autotransplantation of pancreatic islets to the liver (LIVER; n=3);(4) animals with T1D after pancreatectomy, which were autotransplanted with bionic petals (3D-PETALS; n=3).The effectiveness of the transplantation (TX) was assessed by the concentration of glucose, insulin intake and C-peptide. The observation lasted 1 month.
Results: The results showed that in the LIVER group, insulin intake within 3 weeks decreased by 71% compared to the demand before TX. Whereas 1 month after TX, the demand was lower by 62%. The 3D-PETALS group showed that the insulin intake in 3 weeks after TX decreased by 65%, and within a month decreased by 84%. In the 4th week after TX, the insulin intake average in the T1D group was 8.17U, while in the LIVER group=2.44U and in the 3D-PETALS group=1.06U. Islet TX significantly reduced insulin intake (T1D vs LIVER; p=0.0001 and T1D vs 3D-PETALS; p<0.0001). Glucose measurement showed significant changes. After 1 month of follow-up, glucose levels were significantly lower in the LIVER vs T1D (265.8mg% vs 310.2mg%; p<0.0001) and 3D-PETALS & T1D (198.3mg% vs 310.2mg%; p=0.0354). Most importantly, glycemic levels were also significantly lower between the LIVER & 3D PETALS groups (265.8mg% vs 198.3mg%; p=0.0021). The concentration of C-peptide during the study was 0.14ng/ml.
Conclusion: Bioprinted petals with dECM-based bioink significantly reduces diabetic parameters. Thus, it seems to be an effective therapy for people with T1D.
