Long-term physiological flow rescues regressed microvascular networks and increases their longevity

Area of Science:

• Biomedical Engineering
• Microfluidics
• Organ-on-a-Chip Technology

Background:

• Perfusion of microvascular networks (MVNs) is crucial for organ-on-chip models to mature phenotypes and study transport.
• Long-term maintenance of perfusable MVNs is essential for modeling complex biological processes and diseases.

Purpose of the Study:

• To investigate the long-term effects of continuous physiological flow on self-assembled microvascular networks in a microphysiological system (MPS).
• To assess the potential of MPS for modeling long-term, hemodynamically driven processes and chronic diseases.

Main Methods:

• Utilized a microfluidic pump for continuous, recirculating physiological flow through self-assembled MVNs.
• Monitored MVN perfusion, morphology, and flow resistance over 51 days.
• Performed cytokine analysis and bulk RNA sequencing to evaluate cellular responses and remodeling.

Main Results:

• Continuous flow recovered and maintained perfusable MVNs for at least 51 days.
• MVNs remodeled to align with flow direction, achieving homeostasis in maintenance medium without growth factors.
• Flow reduced inflammation, decreased vascular resistance, and induced sustained cellular remodeling.

Conclusions:

• This MPS supports long-term MVN perfusion and remodeling, crucial for advanced organ-on-chip applications.
• The system is suitable for studying hemodynamics, drug distribution, and chronic conditions like inflammation and aging.