Viscous Microcapsules as Microbioreactors to Study Mesenchymal Stem/Stromal Cells Osteolineage Commitment

Abstract

It is essential to design a multifunctional well‐controlled platform to transfer mechanical cues to the cells in different magnitudes. This study introduces a platform, a miniaturized bioreactor, which enables to study the effect of shear stress in microsized compartmentalized structures. In this system, the well‐established cell encapsulation system of liquefied capsules (LCs) is used as microbioreactors in which the encapsulated cells are exposed to variable core viscosities to experience different mechanical forces under a 3D dynamic culture. The LC technology is joined with electrospraying to produce such microbioreactors at high rates, thus allowing the application of microcapsules for high‐throughput screening. Using this platform for osteogenic differentiation as an example, shows that microbioreactors with higher core viscosity which produce higher shear stress lead to significantly higher osteogenic characteristics. Moreover, in this system the forces experienced by cells in each LC are simulated by computational modeling. The maximum wall shear stress applied to the cells inside the bioreactor with low, and high core viscosity environment is estimated to be 297 and 1367 mPa, respectively, for the experimental setup employed. This work outlines the potential of LC microbioreactors as a reliable in vitro customizable platform with a wide range of applications.

Effect of high cyclic hydrostatic pressure on osteogenesis of mesenchymal stem cells cultured in liquefied micro-compartments

“…The observed high resistance of microcapsules makes them an ideal platform for a variety of biomechanical investigations. Consistent with our findings, high mechanical resistance of these liquefied micro-sized capsules was previously reported by performing rotational mechanical stress at 15000 g [ 22 ]. To evaluate whether HHP resulted in any severe cell damage during this period, cells were monitored weakly by live-dead staining and metabolic activity tests.…”

“…A7). The observed high viability is consistent with previous studies which is due to the mild encapsulation process [ 22 , [47] , [48] , [49] , 52 , 60 ].

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“…Moreover, researchers have shown that applying cyclic tensile strain to human MSCs led to osteogenic differentiation without the addition of osteogenic supplements, where a significant increase of BMP-2 expression was observed [ 17 ]. Therefore, mechanical cues can be served as an important inducer to control and manipulate cell functions [ 7 , [18] , [19] , [20] , [21] , [22] ].…”

“…Liquified microcapsules [ [47] , [48] , [49] ], already tested in vivo [ 50 ] , have been developed in our group as a versatile platform that can be employed for various applications. By modifying the configuration, this system can be served as a bone marrow model for recapitulation of osteovascular niches [ 51 ], a tool for investigating various mechanical cues [ 22 , 52 ], or as microbioreactors inducing different shear stresses [ 22 ]. In the proposed system, the encapsulated cells were cultured in contact with surface functionalized microparticles which provided cell attachment sites.…”