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Enhanced Viability for Ex vivo 3D Hydrogel Cultures of Patient-Derived Xenografts in a Perfused Microfluidic Platform
Published on: December 5, 2020
A microperfused incubator for tissue mimetic 3D cultures
Jelena Vukasinovic1, D Kacy Cullen, Michelle C LaPlaca
1Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332-0405, USA. jelena.vukasinovic@me.gatech.edu
Biomedical Microdevices
|June 30, 2009
Summary
A novel microfluidic perfusion platform overcomes nutrient transport limits in high-density 3D cell cultures. This technology enables reproducible tissue engineering and drug discovery by maintaining high cell viability in thick tissue constructs.
Area of Science:
- Biotechnology
- Tissue Engineering
- Microfluidics
Background:
- High-density, three-dimensional (3D) cultures mimic in vivo tissue but face limitations due to intra-culture transport of nutrients and gases.
- Diffusion limits restrict the thickness of dense cultures, hindering reproducible studies and applications in pre-clinical research and tissue engineering.
Purpose of the Study:
- To develop and validate a scalable microfluidic perfusion platform to overcome diffusion limitations in 3D cell cultures.
- To maintain nutrient and gas availability within dense cultures to support high cell density and viability.
Main Methods:
- A novel microfluidic perfusion system was designed to maintain laminar flow, delivering nutrients and removing waste products.
- Microscopic particle image velocimetry was used to measure velocity distributions and 3D flow patterns.
- Neural-astrocytic constructs (700 microm thick) were cultured at brain-like densities (50,000 cells/mm(3)) to validate the platform.
Main Results:
- The microfluidic platform successfully cultured thick neural-astrocytic constructs with 90% viability throughout the full thickness after 2 days of perfusion.
- Unperfused controls showed widespread cell death, highlighting the effectiveness of forced convection laminar perfusion.
- The integrated system maintained physiological temperature (37 +/- 0.2 degrees C) with fast feedback response.
Conclusions:
- The developed microfluidic perfusion platform effectively addresses transport limitations in high-density 3D cultures.
- This technology enables reproducible culturing of tissue equivalents in dynamically controlled environments, enhancing in vitro models for drug discovery and regenerative medicine.
