Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic...

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Microfluidics

Background:

• Engineered microvasculature in vitro, such as perfusable microvascular networks (MVNs), is crucial for studying complex biological processes.
• Current in vitro models often lack long-term stability under standard culture conditions.
• Pure MVNs suffer from limited lifespan without co-culture or protease inhibitors.

Purpose of the Study:

• To introduce a novel strategy for stabilizing microvascular networks (MVNs) using macromolecular crowding (MMC).
• To investigate the biophysical effects of MMC on extracellular matrix deposition and MVN stability.
• To enhance the functionality and lifespan of engineered microvasculature for in vitro studies.

Main Methods:

• Utilized a macromolecular crowding (MMC) strategy with Ficoll macromolecules to stabilize MVNs.
• Applied MMC to microfluidic systems to create engineered microvascular networks.
• Assessed the impact of MMC on cellular junctions, basement membrane components, and cellular contractility.

Main Results:

• MMC significantly enhanced the accumulation of basement membrane components and cellular junctions.
• Reduced cellular contractility was observed, leading to a favorable balance of adhesive forces over tension.
• Stabilized MVNs demonstrated improved vascular barrier function and prolonged lifespan, resembling in vivo microvasculature.

Conclusions:

• Macromolecular crowding (MMC) offers a reliable and versatile method for stabilizing engineered microvessels in microfluidic devices.
• This approach enables the creation of more physiologically relevant in vitro models for microvascular research.
• MMC facilitates the study of microvasculature under simulated physiological conditions with improved stability and function.