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Radial flow hepatocyte bioreactor using stacked microfabricated grooved substrates.
Jaesung Park1, Yawen Li, François Berthiaume
1Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children and Harvard Medical School, Boston, MA 02114, USA.
Biotechnology and Bioengineering
|July 13, 2007
Summary
This study optimized a bioartificial liver (BAL) device using microgrooved substrates. This design enhances hepatocyte function and shows potential for treating liver failure.
Area of Science:
- Biomedical Engineering
- Hepatology
- Tissue Engineering
Background:
- Bioartificial liver (BAL) devices offer temporary support for liver failure.
- Optimizing bioreactor design is crucial for effective hepatocyte function.
- High shear stress in bioreactors can damage cultured hepatocytes.
Purpose of the Study:
- To optimize the flow environment for cultured hepatocytes in a stacked substrate, radial flow bioreactor.
- To investigate the use of microgrooves to protect hepatocytes from shear stress.
- To assess the scalability and potential of the developed BAL device.
Main Methods:
- Microfabrication of concentric grooves on glass substrates using photolithography.
- Finite element analysis to evaluate shear stress and oxygen concentration.
- Perfusion of rat hepatocytes cocultured with fibroblasts in a stacked microgrooved bioreactor.
Main Results:
- Microgrooves protected hepatocytes from high shear stress at necessary flow rates.
- Sufficient oxygen supply was achieved without oxygen-permeable membranes.
- Hepatocyte liver-specific functions (albumin and urea synthesis) remained stable and were significantly increased compared to non-grooved substrates.
Conclusions:
- The radial flow bioreactor with stacked microgrooved substrates is a scalable design.
- This BAL device configuration shows potential for treating liver failure.
- Microgrooved substrates enhance hepatocyte function in bioreactors.
