Microphysiological pancreas-on-chip platform with integrated sensors to model endocrine function and metabolism.
- Resource Type
- Academic Journal
- Authors
- Schlünder K; Department for Microphysiological Systems, Institute of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany. peter.loskill@uni-tuebingen.de.; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.; Cipriano M; Department for Microphysiological Systems, Institute of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany. peter.loskill@uni-tuebingen.de.; Zbinden A; Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.; Fuchs S; Institute for Analytical Chemistry and Food Chemistry, Graz University of Technology, Graz, Austria.; Mayr T; Institute for Analytical Chemistry and Food Chemistry, Graz University of Technology, Graz, Austria.; Schenke-Layland K; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.; Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.; Loskill P; Department for Microphysiological Systems, Institute of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany. peter.loskill@uni-tuebingen.de.; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.; 3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen, Germany.
- Source
- Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101128948 Publication Model: Electronic Cited Medium: Internet ISSN: 1473-0189 (Electronic) Linking ISSN: 14730189 NLM ISO Abbreviation: Lab Chip Subsets: MEDLINE
- Subject
- Language
- English
Pancreatic 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.