02286nas a2200205   4500000000100000000000100001008004100002260001500043100002500058700002200083700001800105700001900123700001700142700002600159700001800185245011600203856007000319520167700389022001402066       2024                            d  c2024-02-231 aKatharina Schlünder1 aMadalena Cipriano1 aAline Zbinden1 aStefanie Fuchs1 aTorsten Mayr1 aKatja Schenke-Layland1 aPeter Loskill00aMicrophysiological pancreas-on-chip platform with integrated sensors to model endocrine function and metabolism  uhttps://pubs.rsc.org/en/content/articlelanding/2024/lc/d3lc00838j3 aPancreatic in vitro research is of major importance to advance mechanistic understanding and development of treatment options for diseases such as diabetes mellitus. We present a thermoplastic-based microphysiological system aiming to model the complex microphysiological structure and function of the endocrine pancreas with concurrent real-time read-out capabilities. The specifically tailored platform enables self-guided trapping of single islets at defined locations: β-cells are assembled to pseudo-islets and injected into the tissue chamber using hydrostatic pressure-driven flow. The pseudo-islets can further be embedded in an ECM-like hydrogel mimicking the native microenvironment of pancreatic islets in vivo. Non-invasive real-time monitoring of the oxygen levels on-chip is realized by the integration of luminescence-based optical sensors to the platform. To monitor insulin secretion kinetics in response to glucose stimulation in a time-resolved manner, an automated cycling of different glucose conditions is implemented. The model's response to glucose stimulation can be monitored via offline analysis of insulin secretion and via specific changes in oxygen consumption due to higher metabolic activity of pseudo-islets at high glucose levels. To demonstrate applicability for drug testing, the effects of antidiabetic medications are assessed and changes in dynamic insulin secretion are observed in line with the respective mechanism of action. Finally, by integrating human pancreatic islet microtissues, we highlight the flexibility of the platform and demonstrate the preservation of long-term functionality of human endocrine pancreatic tissue.  a1473-0189