title: Integrating biological vasculature into a multi-organ-chip microsystem.
abstract: A chip-based system mimicking the transport function of the human cardiovascular system has been established at minute but standardized microsystem scale. A peristaltic on-chip micropump generates pulsatile shear stress in a widely adjustable physiological range within a microchannel circuit entirely covered on all fluid contact surfaces with human dermal microvascular endothelial cells. This microvascular transport system can be reproducibly established within four days, independently of the individual endothelial cell donor background. It interconnects two standard tissue culture compartments, each of 5 mm diameter, through microfluidic channels of 500 μm width. Further vessel branching and vessel diameter reduction down to a microvessel scale of approximately 40 μm width was realised by a two-photon laser ablation technique applied to inserts, designed for the convenient establishment of individual organ equivalents in the tissue culture compartments at a later time. The chip layout ensures physiological fluid-to-tissue ratios. Moreover, an in-depth microscopic analysis revealed the fine-tuned adjustment of endothelial cell behaviour to local shear stresses along the microvasculature of the system. Time-lapse and 3D imaging two-photon microscopy were used to visualise details of spatiotemporal adherence of the endothelial cells to the channel system and to each other. The first indicative long-term experiments revealed stable performance over two and four weeks. The potential application of this system for the future establishment of human-on-a-chip systems and basic human endothelial cell research is discussed.
authors.affiliation: Technische Universität Berlin, Institute of Biotechnology, Department Medical Biotechnology, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schimek
authors.forename: Mathias
authors.initials: M
authors.lastname: Busek
authors.forename: Sven
authors.initials: S
authors.lastname: Brincker
authors.forename: Benjamin
authors.initials: B
authors.lastname: Groth
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Roland
authors.initials: R
authors.lastname: Lauster
authors.forename: Gerd
authors.initials: G
authors.lastname: Lindner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lorenz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Menzel
authors.forename: Frank
authors.initials: F
authors.lastname: Sonntag
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.forename: Uwe
authors.initials: U
authors.lastname: Marx
authors.forename: Reyk
authors.initials: R
authors.lastname: Horland
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D055806:Microvessels / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D033081:Shear Strength; D014841:von Willebrand Factor / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D000099152:Cadherin 5