3.2. Shear stress & Cell culture
The spatial distribution of shear stress levels inside the chip was predicted by COMSOL Multiphysics simulation. The predicted values of shear stress in the gut barrier module ranged between 0.04×10-4 and 1.33×10-4dyne/cm2 (Fig. 4A).. The shear stress levels withinin vivo small intestine are known to be approximately 2.2×10-7 dyne/cm2(Choe, Ha, Choi, Choi, & Sung, 2017). Although our shear stress in the gut barrier module was higher than thatin vivo , Caco-2 cells formed confluent cell layer when co-cultured with the brain endothelial cells (Fig. 5A and 5D). Several gut-on-a-chip studies have reported shear stress higher than in vivo values (Chi et al., 2015; Choe et al., 2017; Kim, Huh, Hamilton, & Ingber, 2012), where the Caco-2 layers got reliable integrity, promoting Caco-2 differentiation (Ashammakhi et al., 2020).
The predicted shear stress levels in the BBB module were 0.01×10-3 - 1.22×10-3dyne/cm2 in the BBB module (Fig. 4B). In contrast, shear stress levels within the brain microvasculature range from 4 to 20 dyne/cm2 (Colgan et al., 2007). Many studies have been conducted at shear stress levels lower than the reported in vivo range, and were able to achieve reliable barrier formation (Oddo et al., 2019). In our study, the brain endothelial cells showed high survival rate with confluent cell layer when co-cultured with Caco-2 (Fig. 5B, 5C, 5E and 5F). Our results show that our GBA chip can support co-culture of gut epithelial and blood endothelial cells.