Abstract
In native fibrocartilage, mechanotransduction allows the cells to perceive the physical microenvironment not only through topographical cues from the extracellular matrix, but also through mechanical cues, such as interstitial flow. To create a microenvironment that simultaneously integrates nanotopography and flow stimulus, we developed a biomimetic microfluidic device embedded with aligned nanofibers to contain microchambers of different angles, which enabled the flow direction to form different angles with the fibers. Using this device, we investigated the effects of microfluidic and nanotopographical environment on the morphology and fibrochondrogenesis of mesenchymal stem cells (MSCs) and the involvement of RhoA/ROCK pathway and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ). The results showed that the flow direction perpendicular to aligned nanofibers was conducive to fibrochondrogenesis of MSCs. In addition, ROCK inhibitor and knockdown of YAP/TAZ disrupted fibrochondrogenic differentiation of MSCs. In conclusion, our data suggest the crucial role of mechanotransduction in regulating fibrochondrogenic differentiation of MSCs, which may be mediated by RhoA/ROCK pathway and YAP/TAZ.
Highlights
Fibrocartilage, especially the meniscus of the knee and the annulus fibrosus of the intervertebral disc, have poor self-repair capability, in avascular regions [1]
We explored the role of RhoA/ ROCK pathway and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) in mesenchymal stem cells (MSCs) fibrochondrogenic differentiation
These results demonstrated that the isolated MSCs were proliferative and pluripotent
Summary
Fibrocartilage, especially the meniscus of the knee and the annulus fibrosus of the intervertebral disc, have poor self-repair capability, in avascular regions [1]. Mesenchymal stem cells (MSCs) have shown promise for regenerative medicine, especially tissue engineering, due to their capacity of self-renewal, proliferation, and pluripotency. Nanofibrous scaffolds, formed by the electrospinning technique, have been widely employed for tissue engineering to mimic the native extracellular matrix (ECM). These scaffolds provide a biomimetic nanotopographical microenvironment capable of modulating cell morphology, differentiation, phenotype, and cytoskeletal organization by virtue of their nano-scale features [8]. Aligned nanofibrous scaffolds can augment matrix content and serve as instructive topographical cues for stem cell fibrochondrogenic differentiation [10]
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