Low intermittent flow promotes rat mesenchymal stem cell differentiation in logarithmic fluid shear device

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone tissue engineering due to their osteogenic potential.
• Mechanical signals, like fluid shear stress, influence BMSC differentiation, but *in vivo* ranges are difficult to replicate.
• Existing devices struggle to generate the wide spectrum of shear stresses experienced biologically.

Purpose of the Study:

• To design and validate a compact microfluidic device capable of generating a wide range of fluid shear stresses.
• To investigate the effects of controlled fluid shear stress on the proliferation and osteogenic differentiation of rat BMSCs (rBMSCs).

Main Methods:

• A novel microfluidic device was engineered using hydraulic resistance and linear optimization to produce four orders of shear stress.
• Numerical simulations determined shear stress ranges from 1.03 Pa to 1.09 mPa at an inlet velocity of 160 μl/min.
• Primary rBMSCs were cultured within the device for four days under varying intermittent shear conditions.

Main Results:

• The microfluidic device successfully generated a logarithmic gradient of shear stresses.
• Enhanced proliferation of rBMSCs was observed under intermittent flow at 1.09 mPa.
• Osteogenic gene upregulation and increased alkaline phosphatase activity were noted at 10 mPa shear stress.

Conclusions:

• The developed microfluidic device offers precise control over shear stress for cell culture applications.
• Intermittent fluid shear stress, particularly around 10 mPa, effectively promotes osteogenic differentiation of rBMSCs.
• This technology holds promise for advancing bone tissue engineering strategies.