Bioink based on the dECM for 3D-bioprinting of bionic pancreas - first results of animal
Marta Klak1,2, Katarzyna Kosowska1, Tomasz Bryniarski1, Ilona Lojszczyk1, Tomasz Dobrzański 2, Grzegorz Tymicki1, Anna Filip1, Andrzej Szczepankiewicz4, Radoslaw Olkowski5, Anna Kosowska6, Andrzej Berman1,2,3, Artur Kaminski5, Michal Wszola1,2,3.
1Foundation of Research and Science Development, Warsaw, Poland; 2Polbionica Ltd., Warsaw, Poland; 3Medispace Medical Centre, Warsaw, Poland; 4Laboratory of Electron Microscopy, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland; 5Department of Transplantology and Central Tissue Bank, Medical University of Warsaw, Warsaw, Poland; 6Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
Biomedical engineering is a fast developing discipline of science which combines the achievements of engineering and life sciences towards restoration and fabrication of complex physiological systems. Hence, the major challenge for biofabrication is mimicking natural extracellular matrix. Thus, bioink based on porcine, pancreatic ECM with semi-synthetic additives was develop. An extensive survey on obtained material was performed in both in vitro and in vivo tests. Petals of bioink with porcine islets was 3D printed and glucose stimulation tests was carried to verify the islets functionality. Insulin secretion assay showed that the bioink served appropriate conditions for islets which secreted significantly more insulin while compared to 2D islets culture. The cytotoxicity test of fabricated bioink on model L929 cell line was run and according to ISO 10993-5, the bioink appeared to be non-cytotoxic. Hence, in vivo experiments on murine model were performed. Animals with transplanted 3D constructs were examined for following parameters: AST, ALT, KC, IL-6 and TNF-α. Experiment took 12 months, and no disturbances of tested parameters were observed. Finally, mechanical properties of 3D printed constructs and their ultrastructure analysis were investigated. We conclude that newly developed bioink is appropriate for extrusion bioprinting and we proved to be non-cytotoxic. Furthermore, it constitutes a favorable conditions for the process of neovascularization which was noticed after 8 weeks after transplantation to animal model.
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