title: Immersed Boundary Models for Quantifying Flow-Induced Mechanical Stimuli on Stem Cells Seeded on 3D Scaffolds in Perfusion Bioreactors.
abstract: Perfusion bioreactors regulate flow conditions in order to provide cells with oxygen, nutrients and flow-associated mechanical stimuli. Locally, these flow conditions can vary depending on the scaffold geometry, cellular confluency and amount of extra cellular matrix deposition. In this study, a novel application of the immersed boundary method was introduced in order to represent a detailed deformable cell attached to a 3D scaffold inside a perfusion bioreactor and exposed to microscopic flow. The immersed boundary model permits the prediction of mechanical effects of the local flow conditions on the cell. Incorporating stiffness values measured with atomic force microscopy and micro-flow boundary conditions obtained from computational fluid dynamics simulations on the entire scaffold, we compared cell deformation, cortical tension, normal and shear pressure between different cell shapes and locations. We observed a large effect of the precise cell location on the local shear stress and we predicted flow-induced cortical tensions in the order of 5 pN/μm, at the lower end of the range reported in literature. The proposed method provides an interesting tool to study perfusion bioreactors processes down to the level of the individual cell's micro-environment, which can further aid in the achievement of robust bioprocess control for regenerative medicine applications.
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.|Biomechanics Research Unit, Université de Liège, Liège, Belgium.
authors.forename: Yann
authors.identifier: http://orcid.org/0000-0002-2733-9587
authors.initials: Y
authors.lastname: Guyot
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.|Division of Mechatronics, Biostatistics and Sensors (MeBioS), Leuven, Belgium.|Biomechanics Section, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.affiliation: Division of Mechatronics, Biostatistics and Sensors (MeBioS), Leuven, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Odenthal
authors.affiliation: Division of Mechatronics, Biostatistics and Sensors (MeBioS), Leuven, Belgium.
authors.forename: Ramesh
authors.identifier: http://orcid.org/0000-0001-5569-2540
authors.initials: R
authors.lastname: Subramani
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.|Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.affiliation: Division of Mechatronics, Biostatistics and Sensors (MeBioS), Leuven, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Ramon
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.|Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papantoniou
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.|Biomechanics Research Unit, Université de Liège, Liège, Belgium.|Biomechanics Section, KU Leuven, Leuven, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Geris