Mathias Busek

https://scholar.google.com/citations?user=qz5x2_EAAAAJ&hl=en

• Delon, Ludivine; Busek, Mathias; Menezes, Pedro Duarte; Gadegaard, Nikolaj; Stokowiec, Justyna & Golovin, Alexey [Show all 10 contributors for this article] (2025). Placental Syncytium-on-Chip (PSoC)–Comparison of Forskolin or Mechanical Induced-Syncytialization. Advanced Healthcare Materials. ISSN 2192-2640. doi: 10.1002/adhm.202404462. Full text in Research Archive Show summary

  The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts and differentiated syncytiotrophoblats, whose maturation and function are influenced by wall shear stress (WSS) from the maternal blood circulation. Most in vitro placenta models rely on cyclic adenosine monophosphate inducer forskolin (FSK) to establish a placental syncytium. Here a trophoblastic BeWo cell line is used to systematically compare the effect of FSK treatment in static culture with WSS stimulation in a pumpless, recirculating organ-on-chip. It is shown that BeWo cells undergo a similar differentiation under WSS exposure to FSK treatment. A WSS of 0.1 dyn cm−2 leads to cell fusion, polarization, barrier functions, human chorionic gonadotropin (β-hCG) secretion, and increased expression of key transporters. Moreover, WSS induces favorable changes in the levels of FMS-like tyrosine kinase-1 (FLT-1) and Placental Growth Factor (PlGF) suggesting the development of a physiologically relevant placental syncytium-on-chip (PSoC) without the need for FSK. The platform is further expanded to a syncytiotrophoblast/endothelial co-culture showing physiological vascular functions under WSS. The forskolin-free PSoC presented here represents the first pumpless recirculating and scalable platform for physiological placental studies and drug testing.

• Kogler, Stian; Pedersen, Gustav Mathingsdal; Martínez-Ramírez, Felipe; Aizenshtadt, Aleksandra; Busek, Mathias & Krauss, Stefan Johannes Karl [Show all 8 contributors for this article] (2024). An FDA-Validated, Self-Cleaning Liquid Chromatography–Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium. Analytical Chemistry. ISSN 0003-2700. 96(29), p. 12129–12138. doi: 10.1021/acs.analchem.4c02246. Full text in Research Archive Show summary

  As organoids and organ-on-chip (OoC) systems move toward preclinical and clinical applications, there is an increased need for method validation. Using a liquid chromatography–mass spectrometry (LC–MS)-based approach, we developed a method for measuring small-molecule drugs and metabolites in the cell medium directly sampled from liver organoids/OoC systems. The LC–MS setup was coupled to an automatic filtration and filter flush system with online solid-phase extraction (SPE), allowing for robust and automated sample cleanup/analysis. For the matrix, rich in, e.g., protein, salts, and amino acids, no preinjection sample preparation steps (protein precipitation, SPE, etc.) were necessary. The approach was demonstrated with tolbutamide and its liver metabolite, 4-hydroxytolbutamide (4HT). The method was validated for analysis of cell media of human stem cell-derived liver organoids cultured in static conditions and on a microfluidic platform according to Food and Drug Administration (FDA) guidelines with regards to selectivity, matrix effects, accuracy, precision, etc. The system allows for hundreds of injections without replacing chromatography hardware. In summary, drug/metabolite analysis of organoids/OoCs can be performed robustly with minimal sample preparation.

• Menezes, Pedro Duarte; Hunter, Alisha; Dickson, Thomas; Hecht, Soren; Kumar, Charchit & Busek, Mathias [Show all 8 contributors for this article] (2024). Scalable, Transparent, and Micro: 3D-Printed Rapid Tooling for Injection Molded Microfluidics. Advanced Engineering Materials. ISSN 1438-1656. 26(20). doi: 10.1002/adem.202400276. Full text in Research Archive
• Aizenshtadt, Aleksandra; Wang, Chencheng; Abadpour, Shadab; Menezes, Pedro Duarte; Wilhelmsen, Ingrid & Dalmao-Fernandez, Andrea [Show all 15 contributors for this article] (2024). Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver. Advanced Healthcare Materials. ISSN 2192-2640. 13(13). doi: 10.1002/adhm.202303785. Full text in Research Archive Show summary

  Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump-less recirculating organ-on-chip platform that combines human pluripotent stem cell (sc)-derived sc-liver and sc-islet organoids is presented. The platform reproduces key aspects of the metabolic cross-talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc-islet and sc-liver organoids while preserving a reduced release of pro-inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc-liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc-islets produce pro-inflammatory cytokines on-chip. Finally, the platform reproduces known effects of anti-diabetic drugs on-chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on-chip, as well as for testing potential therapeutic interventions.

• Olsen, Christine; Wang, Chencheng; Aizenshtadt, Aleksandra; Abadpour, Shadab; Lundanes, Elsa & Skottvoll, Frøydis Sved [Show all 11 contributors for this article] (2023). Simultaneous LC–MS determination of glucose regulatory peptides secreted by stem cell–derived islet organoids. Electrophoresis. ISSN 0173-0835. 44(21-22), p. 1682–1697. doi: 10.1002/elps.202300095. Full text in Research Archive Show summary

  Abstract For studying stem cell–derived islet organoids (SC‐islets) in an organ‐on‐chip (OoC) platform, we have developed a reversed‐phase liquid chromatography–tandem mass spectrometry (RPLC–MS/MS) method allowing for simultaneous determination of insulin, somatostatin‐14, and glucagon, with improved matrix robustness compared to earlier methodology. Combining phenyl/hexyl‐C18 separations using 2.1 mm inner diameter LC columns and triple quadrupole mass spectrometry, identification and quantification were secured with negligible variance in retention time and quantifier/qualifier ratios, negligible levels of carryover (<2%), and sufficient precision (±10% RSD) and accuracy (±15% relative error) with and without use of an internal standard. The obtained lower limits of quantification were 0.2 µg/L for human insulin, 0.1 µg/L for somatostatin‐14, and 0.05 µg/L for glucagon. The here‐developed RPLC–MS/MS method showed that the SC‐islets have an insulin response dependent on glucose concentration, and the SC‐islets produce and release somatostatin‐14 and glucagon. The RPLC–MS/MS method for these peptide hormones was compatible with an unfiltered offline sample collection from SC‐islets cultivated on a pumpless, recirculating OoC (rOoC) platform. The SC‐islets background secretion of insulin was not significantly different on the rOoC device compared to a standard cell culture well‐plate. Taken together, RPLC–MS/MS method is well suited for multi‐hormone measurements of SC‐islets on an OoC platform.

• Busek, Mathias; Aizenshtadt, Aleksandra; Koch, Timo; Frank, Anna; Delon, Ludivine Sylvie Claude & Martinez, Mikel Amirola [Show all 12 contributors for this article] (2023). Pump-less, recirculating organ-on-a-chip (rOoC) platform. Lab on a Chip. ISSN 1473-0197. doi: 10.1039/D2LC00919F. Full text in Research Archive
• Busek, Mathias; Aizenshtadt, Aleksandra; Martinez, Mikel Amirola; Delon, Ludivine Sylvie Claude & Krauss, Stefan Johannes Karl (2022). Academic User View: Organ-on-a-Chip Technology. Biosensors. ISSN 2079-6374. 12(2). doi: 10.3390/bios12020126. Full text in Research Archive Show summary

  The pleasantness of gentle stroking (CT-targeted touch) varies highly between individuals and studies, indicating that relevant factors may not be accounted for. We propose that the affective value of a touch event is determined by how well its perceived purpose matches the goals of the touch receiver. The perceived purpose or meaning of touch is in turn informed by the sensory characteristics together with the setting, person factors, and the touchee’s expectations. Affective touch is often a sign of affection, intended to soothe or show support. In a typical lab study however, the toucher is a stranger and its purpose is research. The purpose of laboratory touch is nevertheless compatible with the goal of participants, namely to contribute to research. To fully understand how the perception of affective touch emerges, more studies should directly manipulate participants’ beliefs about the purpose of touch.

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• Busek, Mathias (2024). Scientia Podcast. [Internet]. https://www.med.uio.no/english/research/scientia-fellows/new. Full text in Research Archive
• Busek, Mathias (2024). Pump-less recirculating Organ-on-Chip (rOoC) platform – a versatile platform for biomedical research. Full text in Research Archive
• Busek, Mathias (2024). The pumpless recirculating Organon-Chip platform – a versatile platform for improved organoid loading. Full text in Research Archive
• Busek, Mathias (2024). Organ-on-chip meets sensor technology - applications and use-cases for (bio) sensors in preclinical testing. Full text in Research Archive
• Busek, Mathias (2023). Organ-on-a-chip interview by Inven2. [Internet]. https://www.inven2.com/organ-on-a-chip/. Full text in Research Archive
• Busek, Mathias (2023). Cellspace: The revolving Organ-on-Chip (rOoC) platform. Full text in Research Archive
• Busek, Mathias (2023). Pump-less Organ-on-a-Chip platform: A versatile tool for cell biological research. Full text in Research Archive
• Busek, Mathias (2023). Pump-less Organ-on-chip platform for the functional co-culture of human circulating immune cells and 3D liver tissue representations. Full text in Research Archive
• Busek, Mathias (2023). The Pumpless-recirulating Organ-on-Chip platform (rOoC). Full text in Research Archive

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