Microscale multilayer cocultures for biomimetic blood vessels

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Microfluidics

Background:

• Living tissues exhibit complex, organized microstructures.
• Existing in vitro microscale systems are predominantly 2D, limiting the study of 3D cellular environments.
• There is a need for advanced 3D models that mimic in vivo tissue complexity.

Purpose of the Study:

• To demonstrate a novel 3D hierarchical biomimetic multilayer microsystem.
• To develop a generally applicable technique for fabricating 3D cell-laden microstructures.
• To create an in vitro model for studying 3D cell-cell and cell-matrix interactions.

Main Methods:

• Utilized layer-by-layer microfluidics to construct multilayered systems.
• Patterned cells and biopolymers in microchannels, controlling the x, y, and z dimensions.
• Fabricated a prototype mimicking a blood vessel wall using three vascular cell types and heterogeneous biopolymers.

Main Results:

• Revealed the impact of matrix composition and multilayer configurations on 3D cell interactions and biology.
• Observed cell migration in the z-dimension, matrix remodeling, intercellular adhesion molecule expression, and actin organization.
• Demonstrated that more biomimetic cocultures yield more stable structures and in vivo-like functions.

Conclusions:

• The developed technique enables the fabrication of microscale hierarchical 'neotissues' with 3D control over matrix and cell types.
• This approach provides a valuable in vitro coculture model for investigating complex 3D cellular processes.
• The 3D microsystem advances the ability to study cell-matrix and cell-cell interactions in a physiologically relevant context.