A Microfluidic-Based Multi-Shear Device for Investigating the Effects of Low Fluid-Induced Stresses on Osteoblasts

Yu, Weiliang; Qu, Hong; Hu, Guoqing; Zhang, Qian; Song, Kui; Guan, Haijie; Liu, Tingjiao; Qin, Jianhua

doi:10.1371/journal.pone.0089966

Cited by 62 publications

(54 citation statements)

References 37 publications

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“…Fluid flow can also be controlled by pumps generating unidirectional (Reich and Frangos, 1991; Genetos et al, 2004), pulsatile (Reich and Frangos, 1991; Hillsley and Frangos, 1997; Klein-Nulend et al, 1997; Bacabac et al, 2004), and oscillatory (Jacobs et al, 1998; Lu et al, 2012) flow profiles. Physiologically relevant wall shear stresses in the range of 0.001–3 Pa can be generated with PPFC (Yu et al, 2014). In particular, the application of very high shear rates is an advantage of PPFC compared to other systems.…”

Section: Bone Mechanotransductionmentioning

confidence: 99%

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In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation

Wittkowske

Reilly

Lacroix

et al. 2016

Front. Bioeng. Biotechnol.

226

225

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This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

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Section: Bone Mechanotransductionmentioning

confidence: 99%

“…For example, Yu et al (2014) designed a complex microfluidic network consisting of relatively large cell culture chambers. They were able to generate different FSS on the same chip by using different widths and lengths of the inlet channels.…”

Section: Bone Mechanotransductionmentioning

confidence: 99%

In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation

Wittkowske

Reilly

Lacroix

et al. 2016

Front. Bioeng. Biotechnol.

226

225

View full text Add to dashboard Cite

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“…The microfluidic technology has attracted increasing interests in fluidic shear stress-related biological applications with precise control of liquid at micro-scale, reduced reagents consumption, and the ability to model the physiologically relevant flow microenvironment in vivo. [23][24][25] However, few works are devoted to the study of MSCs mechanical responses under multiple extremely low fluidic shear stresses equivalent to interstitial level of flows on a microfluidic device.…”

Section: Regulation Of Cell Migration and Osteogenic Differentiation mentioning

confidence: 99%

Regulation of cell migration and osteogenic differentiation in mesenchymal stem cells under extremely low fluidic shear stress

Gao

Zhang

et al. 2014

Biomicrofluidics

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Mesenchymal stem cells (MSCs) are multipotent stem cells predominantly obtained from bone marrow, which are sensitive to mechanical loadings in physiological microenvironment. However, how the MSCs sense and respond to extremely low fluidic shear stress analogous to interstitial flow in vivo is poorly understood. In this work, we present a functional microfluidic device to examine the migration and differentiation behaviors of MSCs in response to multiple orders of physiologically relevant interstitial flow levels. The different magnitudes of fluid flow-induced shear stress were produced by a hydraulic resistance-based microfluidic perfusion system consisting of a microchannel network and a parallel of uniform cell culture chambers. By changing the length and width of the flow-in channels, the multiple magnitudes of low shear stresses could be generated ranging from ∼10−5 to ∼10−2 dyne/cm2. We demonstrated enhanced significant F-actin expression and cell migration in MSCs under applied fluidic shear stress at ∼10−2 dyne/cm2. We also demonstrated a significant osteogenic differentiation under this interstitial level of slow flows from ∼10−2 to ∼10−4 dyne/cm2 in MSCs by analyzing alkaline phosphatase activity and osteopontin staining. Moreover, cytochalasin D and Rho-inhibitor Y-27632 significantly reduced the cytoskeleton F-actin expression and osteogenic differentiation in MSCs, indicating the mediated mechanical responses of MSCs under extremely low fluidic shear stress, possibly as a consequence of Rho-associated kinase pathway. The established microfluidic perfusion system with multiple shear-flow capabilities is simple and easy to operate, providing a flexible platform for studying the responses of diverse types of cells to the multiple interstitial flow levels in a single assay.

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“…15 Though microfluidic devices in which shear stress can be applied to cells have been reported. 16,17 However, most papers reported results of under 10-dyn/cm 2 (1.0-Pa) conditions, and there are no reports on high shear stress conditions adaptable to PH model. In this study, we developed a microdevice that can withstand high shear stress, and developed a technique for cell recovery from the channel.…”

Section: Introductionmentioning

confidence: 99%

Fluidic Culture and Analysis of Pulmonary Artery Smooth Muscle Cells for the Study of Pulmonary Hypertension

et al. 2016

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There is an urgent need to develop novel in-vitro models to mimic the disease conditions in pulmonary hypertension (PH). We developed a microfluidic cell culture device for PH studies that withstood high shear stress. Techniques were also developed for cell recovery from the microchannel and mRNA isolation from the collected cells. Using this device, we found that shear stress caused a 7.5-fold increase in the transcription levels of a PH-related molecule, Cyclin D1.

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A Microfluidic-Based Multi-Shear Device for Investigating the Effects of Low Fluid-Induced Stresses on Osteoblasts

Cited by 62 publications

References 37 publications

In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation

In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation

Regulation of cell migration and osteogenic differentiation in mesenchymal stem cells under extremely low fluidic shear stress

Fluidic Culture and Analysis of Pulmonary Artery Smooth Muscle Cells for the Study of Pulmonary Hypertension

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