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Design, fabrication, and characterization of a microbubble array microphysiological system.

Lukas B Jenkins1, Hasibul Hasan Hredoy1, Hossein Abolhassani1

  • 1Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.

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Summary
This summary is machine-generated.

This study introduces a novel microbubble-fluidic system for 3D tissue culture, improving nutrient delivery and preserving tissue fidelity under high flow rates for drug discovery.

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Area of Science:

  • Biotechnology
  • Tissue Engineering
  • Microfluidics

Background:

  • Microphysiological systems (MPS) are crucial for high-throughput 3D tissue culture and drug screening.
  • Microbubbles (MBs) offer a unique format for integration into MPS.
  • Current MPS face challenges in nutrient delivery, waste removal, and maintaining physiological relevance.

Purpose of the Study:

  • To develop and validate a hybrid microbubble-fluidic MPS for enhanced 3D tissue culture.
  • To investigate the impact of fluid dynamics on tissue culture within MBs.
  • To demonstrate the utility of this platform for drug discovery and toxicology.

Main Methods:

  • Computational fluid dynamics (CFD) simulations to model flow and solute diffusion within MBs.
  • Optical tracking of microspheres to validate CFD simulations.
  • Fabrication of a millifluidic MB device using 3D printing (FDM) and molding.
  • Culture of murine salivary gland tissues under dynamic flow conditions.

Main Results:

  • CFD simulations revealed significant velocity decoupling and shear dampening within MBs, allowing high channel flow rates while maintaining low-shear environments.
  • MBs with aspect ratios between 2 and 3 optimized nutrient transport and retention of cell-secreted factors.
  • 3D printed MB devices maintained tissue fidelity, evidenced by preserved gene expression in cultured salivary gland tissues.
  • The hybrid system prevented tissue dislodgement under high flow and outperformed rectilinear wells in preventing lactate accumulation.

Conclusions:

  • The novel MB-fluidic MPS platform enables scalable, high-content 3D culture with improved physiological relevance.
  • This technology enhances nutrient/waste exchange and preserves tissue integrity, overcoming limitations of traditional microfluidic systems.
  • The platform is suitable for organoid, tumor spheroid, and tissue mimetic applications in drug discovery and toxicology.