Fluid flow-induced cell stimulation in bone tissue engineering changes due to interstitial tissue formation in vitro

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Computational Modeling

Background:

• Bioreactors apply wall shear stress (WSS) to cells in tissue engineering.
• In silico models are crucial for bioreactor design and understanding cellular responses.
• Previous bone tissue engineering (BTE) models focused on appositional growth, neglecting interstitial tissue formation.

Purpose of the Study:

• To quantify WSS and mechanical strain on cells during interstitial tissue formation in BTE.
• To investigate the influence of varying interstitial tissue morphologies on WSS.
• To compare mechanical stimuli with established mechanobiological thresholds for osteogenesis.

Main Methods:

• Utilized a multiscale fluid-solid interaction model.
• Simulated interstitial tissue formation within a BTE bioreactor experiment.
• Quantified WSS and mechanical strain on cells under constant perfusion flow.

Main Results:

• Observed high variation in WSS across different interstitial tissue morphologies.
• Found that 35% pore filling by mineralized bone tissue correlated with increased average WSS (1.530 to 5.735 mPa over 28 days).
• Mechanical strain on cells was extremely low (10^-14 - 10^-15), significantly below osteogenesis thresholds (e.g., 10^-2).

Conclusions:

• WSS significantly varies with interstitial tissue morphology in BTE.
• The study provides insights into WSS dynamics during interstitial tissue growth.
• Results offer a basis for optimizing micro-fluidic conditions to enhance interstitial tissue mineralization.