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A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic,

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A new PREDICT-96 platform using microphysiological systems (MPS) enhances primary human hepatocyte (PHH) function and longevity. This liver-on-chip model improves drug metabolism studies and disease modeling through recirculating flow.

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Area of Science:

  • Biotechnology
  • Cell Biology
  • Drug Discovery

Background:

  • Microphysiological systems (MPS) offer advanced models for studying organ-specific functions, crucial for disease modeling and drug screening.
  • Liver-on-chip models are essential for understanding drug metabolism and hepatic microenvironments.
  • Novel thermoplastic, oxygen-permeable MPS have been developed for primary human hepatocyte (PHH) culture.

Purpose of the Study:

  • To adapt and extend a novel MPS for primary human hepatocyte (PHH) culture into a 96-well format with recirculating flow.
  • To evaluate the impact of recirculating flow on the metabolic and secretory functions of PHHs in the developed platform.
  • To establish a long-term culture system for PHHs that mimics in vivo mass transport and allows for chronic stimulation studies.

Main Methods:

  • Development of the PREDICT-96 platform, integrating a 96 microfluidic array and an ultra-low volume, re-circulating pumping system.
  • Culture of primary human hepatocytes (PHHs) in the PREDICT-96 array under static conditions, followed by the introduction of recirculating flow.
  • Assessment of PHH metabolic and secretory functions, and cell maintenance over 10 days of continuous flow culture.

Main Results:

  • The PREDICT-96 platform successfully cultured PHHs, maintaining their functions over 10 days with recirculating flow.
  • Recirculating flow significantly increased the metabolic and secretory functions of PHHs compared to static culture.
  • The system allows for long-term culture and the study of cellular responses to chronic stimuli, mimicking in vivo conditions.

Conclusions:

  • The PREDICT-96 platform, featuring a 96-well microfluidic array and recirculating pump, effectively supports long-term culture of primary human hepatocytes (PHHs).
  • This liver-on-chip model enhances PHH metabolic and secretory functions, making it suitable for drug screening and disease modeling.
  • Future developments may include incorporating multiple cell types and integrating high-throughput analytical tools for comprehensive hepatic studies.