The technology of 3D printing of bionic organs gives an opportunity to solve the problems of classical transplantology, such as the shortage of organs, complications of immunosuppression or rejection. After printing, the bionic pancreas requires an optimal environment conditioning the process of its maturation, which consists in the colonization of the produced vessels with endothelial cells and the tubularization of the endothelium within the microcirculation. After the maturation process is completed, it is necessary to evaluate the resulting organ in terms of its functionality and safety.
In order to minimize the risk of contamination while ensuring the necessary functionalities, a bioreactor was created that allows the maturation of the bionic pancreas, and after the end of the process, functional assessment using the semi-automatic Glucose-Stimulated Insulin Secretion (GSIS) test and the assessment of vascular tightness using the pressure test.
10 procedures of maturation and bionic pancreas evaluation were performed using a bioreactor. 5 pancreas contained human beta cells (450000000 cells) and 5 pancreas contained porcian isolated pancreatic islets (75,000 IEq). The mean pancreatic maturation time was 23 hours (2-72 hours). The effectiveness of adhesion of endothelial cells to the vascular wall and tubularization of endothelial cells was assessed by immunohistochemistry. The GSIS test was performed by automatically replacing the medium with glucose at various concentrations. The integrity of the vascular system was assessed by maintaining a pressure of 190 mmHg for 5 minutes.
The adhesion of endothelial cells to the bioink was observed after 1 hour. Tubularization of the endothelium was observed after 48 hours. Insulin secretion upon stimulation with glucose was observed without delay to the control (beta cells or islets) and the insulin concentration during the observation showed a constant ratio compared to the control, but without a clear peak at high glucose concentration. In 8 out of 10 pancreas, no vascular leakage was observed during the pressure test. No material contamination was observed during pancreatic perfusion.
The use of a dedicated bioreactor enables safety during the bionic maturation process of the organ, while allowing for an effective assessment of the organ's functionality and the tightness of the vascular system.