3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis.

Area of Science:

• Biomedical Engineering
• In Vitro Modeling
• Drug Development

Background:

• Physiologic in vitro models are crucial for understanding complex biological processes.
• Existing models often lack the ability to replicate tissue-tissue interactions and continuous perfusion.
• 3D microtissue platforms offer potential for more accurate drug testing.

Purpose of the Study:

• To develop and validate a novel 3D microtissue-based multi-tissue device for studying tissue-tissue interactions.
• To assess the impact of continuous perfusion and co-culture on drug response.
• To demonstrate the utility of the platform for drug bio-activation studies.

Main Methods:

• A flexible 3D microfluidic device with interconnected microchambers was designed.
• Spherical rat liver and colorectal tumor microtissues were cultured under continuous perfusion using gravity-driven flow via chip-tilting.
• Co-cultures were treated with the pro-drug cyclophosphamide for 8 days.
• Drug effects were compared between perfused co-cultures and static cultures with supernatant transfer.

Main Results:

• The developed device enabled robust co-culture of liver and tumor microtissues.
• Continuous perfusion and tissue interaction were essential for observing the bio-activation of cyclophosphamide by liver microtissues.
• The pro-drug significantly impacted tumor growth only in the perfused co-culture system.
• Static culture with pipetted supernatant did not yield significant anti-tumor effects.

Conclusions:

• The novel multi-tissue device effectively supports tissue-tissue interactions and continuous perfusion.
• This platform highlights the critical role of liver bio-activation in drug efficacy.
• The system demonstrates significant utility for in vitro drug development and personalized medicine research.