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The Fluidic Shear Stress Loading Method Enables Mechanobiological Stimulation in an On-Chip Pump-Integrated

Jin Hong Yap1, Satoshi Ishizaki1, Hiroko Nakamura2

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Summary
This summary is machine-generated.

New attachments for microphysiological systems (MPSs) enable fluidic shear stress application, enhancing cell barrier function in organ-on-a-chip models for drug development and mechanobiology research.

Keywords:
BioStellar™ platefluidic shear stress (FSS)microphysiological system (MPS)organ-on-a-chip

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Area of Science:

  • Biotechnology
  • Cell Biology
  • Biomedical Engineering

Background:

  • Microphysiological systems (MPSs) like organ-on-a-chip platforms offer alternatives to animal testing for drug development.
  • The BioStellar™ Plate, a commercial MPS, lacks fluidic shear stress application due to its open-top design, limiting its physiological relevance.
  • Fluidic shear stress is crucial in vivo, influencing cell behavior and function.

Purpose of the Study:

  • To develop and validate fluidic shear stress attachments for the BioStellar™ Plate MPS platform.
  • To enable controlled mechanical stimulation of cells within the MPS.
  • To investigate the impact of fluidic shear stress on cell barrier function.

Main Methods:

  • Designed and fabricated two fluidic shear stress attachments (FSSA-D and FSSA-I) for the BioStellar™ Plate.
  • Utilized COMSOL Multiphysics for flow dynamics simulation to estimate shear stress.
  • Validated attachments via fluorescent bead tracking and biological assays, including TEER measurements with Caco-2 cells.

Main Results:

  • Both FSSA-D and FSSA-I attachments successfully applied controlled fluidic shear stress to cells.
  • Experiments showed enhanced cell barrier function in intestinal epithelial cells (Caco-2) under fluidic shear stress.
  • Transepithelial electrical resistance (TEER) measurements indicated improved barrier integrity.

Conclusions:

  • The developed attachments are practical tools for applying fluidic shear stress in MPS platforms.
  • These attachments advance mechanobiology research by enabling the study of shear stress effects on cells in vitro.
  • The findings support the use of these attachments for more physiologically relevant drug development and research using MPS.