Vascularized pancreas-on-a-chip device produced using a printable simulated extracellular matrix

Abstract

The extracellular matrix (ECM) influences cellular behavior, function, and fate. The ECM surrounding Langerhans islets has not been investigated in detail to explain its role in the development and maturation of pancreatic β-cells. Herein, a complex combination of the simulated ECM (sECM) has been examined with a comprehensive analysis of cell response and a variety of controls. The most promising results were obtained from group containing fibrin, collagen type I, Matrigel®, hyaluronic acid, methylcellulose, and two compounds of functionalized, ionically crosslinking bacterial cellulose (sECMbc). Even though the cell viability was not significantly impacted, the performance of group of sECMbc showed 2 to 4× higher sprouting number and length, 2 to 4× higher insulin secretion in static conditions, and 2 to 10× higher gene expression of VEGF-A, Endothelin-1, and NOS3 than the control group of fibrin matrix (sECMf). Each material was tested in a hydrogel-based, perfusable, pancreas-on-a-chip device and the best group—sECMbc has been tested with the drug Sunitinib to show the extended possibilities of the device for both diabetes-like screening as well as PDAC chemotherapeutics screening for potential personal medicine approach. It proved its functionality in seven days dynamic culture and is suitable as a physiological tissue model. Moreover, the device with the pancreatic-like spheroids was 3D bioprintable and perfusable.