title: A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids.
abstract: A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Massai
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Isu
authors.affiliation: Department of Clinical and Experimental Medicine, Università degli Studi di Parma, Parma, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Madeddu
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cerino
authors.affiliation: Department of Clinical and Experimental Medicine, Università degli Studi di Parma, Parma, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Falco
authors.affiliation: Department of Clinical and Experimental Medicine, Università degli Studi di Parma, Parma, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Frati
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Gallo
authors.affiliation: Istituto Dalle Molle di studi sull'Intelligenza Artificiale, Scuola universitaria professionale della Svizzera italiana, Università della Svizzera italiana, Manno, Switzerland.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Deriu
authors.affiliation: Bioexpansys Srl, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Falvo D'Urso Labate
authors.affiliation: Department of Clinical and Experimental Medicine, Università degli Studi di Parma, Parma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Audenino
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Morbiducci
mesh_terms: D055592:Biophysical Phenomena; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004867:Equipment Design; D006801:Humans; D057446:Hydrodynamics; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D018874:Spheroids, Cellular / Q000166:cytology*; D014407:Tumor Cells, Cultured / Q000166:cytology*