Local extensional flows promote long-range fiber alignment in 3D collagen hydrogels

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Biophysics

Background:

• Type I collagen (COL1) fibers in the extracellular matrix naturally align due to biophysical forces, influencing cell behavior and tissue development.
• Aligned COL1 domains are crucial for processes like tumor cell migration and angiogenesis.
• Previous methods used shear flow to align thin COL1 matrices (<50 µm) in microfluidic devices, but aligning thicker 3D hydrogels (>130 µm) remained challenging.

Purpose of the Study:

• To investigate the role of shear and extensional flows in aligning 3D atelopeptide collagen type I (COL1) hydrogels.
• To develop an advanced microfluidic platform for fabricating aligned 3D COL1 hydrogels with enhanced biofabrication capabilities.

Main Methods:

• Investigated the alignment of 3D atelo COL1 hydrogels under pure shear flow and combined shear-extensional flow.
• Introduced a novel magnetically coupled modular platform for microfluidic cell culture and hydrogel fabrication.
• Utilized layer-by-layer fabrication with specialized modules to create multi-layered COL1 matrices.

Main Results:

• Pure shear flow did not induce significant fiber alignment in 3D COL1 hydrogels.
• The addition of local extensional flow effectively promoted fiber alignment in 3D COL1 hydrogels, maintained over several millimeters.
• The degree of fiber alignment correlated directly with the extensional strain rate.
• The modular platform successfully enabled cell patterning and multi-layered COL1 matrix fabrication.

Conclusions:

• Extensional flow is key for achieving aligned 3D COL1 hydrogels, overcoming limitations of shear flow alone.
• The developed magnetically coupled platform offers a versatile and user-friendly method for advanced hydrogel microengineering.
• This approach integrates fiber alignment with biofabrication, paving the way for more sophisticated tissue models and regenerative medicine applications.