A Novel Mechanical Bioreactor System Allowing Simultaneous Strain and Fluid Shear Stress on Cell Monolayers

2011 ◽  
Author(s):  
W. Scott Van Dyke ◽  
Eric Nauman ◽  
Ozan Akkus
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Fluid Shear Stress ◽  
Compressive Strain ◽  
Bone Adaptation ◽  
Bone Architecture ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Loading Mode

The causes, mechanisms, and biology of bone adaptation have been under intense investigation ever since Julius Wolff proposed that bone architecture is determined by mathematical laws as a result of mechanical loading. How bone responds to mechanical loads by converting the mechanical signals into chemical signals is known as mechanotransduction. The in vivo environment of bone is complex, and most studies of cell-level phenomena have relied on the use of in vitro experiments using mechanical bioreactors. The main types of bioreactors are fluid flow shear stress, tensile and/or compressive strain, and hydrostatic pressure [1–2]. Of these bioreactors, the most intuitive mechanical stimulus for bone would be the tensile and compressive strain bioreactors. However, many researchers now claim that shear stress via interstitial fluid flow in the lacunar-canalicular porosity is the primary mechanosensory stimulus [3]. A handful of studies have attempted to compare the effects of both of these mechanical stimuli on osteoblasts, but these studies are lacking in two respects [4–6]. First, if both fluid flow and strain are performed in the same bioreactor, the magnitude of one loading mode is explicitly determined through constitutive equations, while the other is only estimated. Second, if the magnitudes of the loading modes are able to be explicitly determined they are performed in different bioreactors, providing the cells different extracellular environments. Therefore, a highly controllable dual-loading mode mechanical bioreactor, as described and characterized in this study, is a necessary tool to further understand the mechanotransduction of bone.

scholarly journals Finite element study of stem cells under fluid flow for mechanoregulation toward osteochondral cells

2021 ◽  
Vol 32 (7) ◽  
Author(s):  
Mehdi Moradkhani ◽  
Bahman Vahidi ◽  
Bahram Ahmadian
Keyword(s):  
Stem Cells ◽  
Shear Stress ◽  
Fluid Flow ◽  
Computational Simulation ◽  
Hydrodynamic Pressure ◽  
Mechanical Stimuli ◽  
Pore Architecture ◽  
Proliferation And Differentiation

AbstractInvestigating the effects of mechanical stimuli on stem cells under in vitro and in vivo conditions is a very important issue to reach better control on cellular responses like growth, proliferation, and differentiation. In this regard, studying the effects of scaffold geometry, steady, and transient fluid flow, as well as influence of different locations of the cells lodged on the scaffold on effective mechanical stimulations of the stem cells are of the main goals of this study. For this purpose, collagen-based scaffolds and implicit surfaces of the pore architecture was used. In this study, computational fluid dynamics and fluid-structure interaction method was used for the computational simulation. The results showed that the scaffold microstructure and the pore architecture had an essential effect on accessibility of the fluid to different portions of the scaffold. This leads to the optimization of shear stress and hydrodynamic pressure in different surfaces of the scaffold for better transportation of oxygen and growth factors as well as for optimized mechanoregulative responses of cell–scaffold interactions. Furthermore, the results indicated that the HP scaffold provides more optimizer surfaces to culture stem cells rather than Gyroid and IWP scaffolds. The results of exerting oscillatory fluid flow into the HP scaffold showed that the whole surface of the HP scaffold expose to the shear stress between 0.1 and 40 mPa and hydrodynamics factors on the scaffold was uniform. The results of this study could be used as an aid for experimentalists to choose optimist fluid flow conditions and suitable situation for cell culture.

Novel in vitro microfluidic platform for osteocyte mechanotransduction studies

2020 ◽  
Vol 12 (12) ◽  
pp. 303-310
Author(s):  
Liangcheng Xu ◽  
Xin Song ◽  
Gwennyth Carroll ◽  
Lidan You
Keyword(s):  
Shear Stress ◽  
Drug Targets ◽  
Fluid Shear Stress ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Bone Cell ◽  
Interstitial Fluid Flow ◽  
Molecule Transport ◽  
Flow Shear Stress

Abstract Osteocytes are the major mechanosensing cells in bone remodeling. Current in vitro bone mechanotransduction research use macroscale devices such as flow chambers; however, in vitro microfluidic devices provide an optimal tool to better understand this biological process with its flexible design, physiologically relevant dimensions and high-throughput capabilities. This project aims to design and fabricate a multi-shear stress, co-culture platform to study the interaction between osteocytes and other bone cells under varying flow conditions. Standard microfluidic design utilizing changing geometric parameters is used to induce different flow rates that are directly proportional to the levels of shear stress, with devices fabricated from standard polydimethylsiloxane (PDMS)-based softlithography processes. Each osteocyte channel (OCY) is connected to an adjacent osteoclast channel (OC) by 20-μm perfusion channels for cellular signaling molecule transport. Significant differences in RANKL levels are observed between channels with different shear stress levels, and we observed that pre-osteoclast differentiation was directly affected by adjacent flow-stimulated osteocytes. Significant decrease in the number of differentiating osteoclasts is observed in the OC channel adjacent to the 2-Pa shear stress OCY channel, while differentiation adjacent to the 0.5-Pa shear stress OCY channel is unaffected compared with no-flow controls. Addition of zoledronic acid showed a significant decrease in osteoclast differentiation, compounding to effect instigated by increasing fluid shear stress. Using this platform, we are able to mimic the interaction between osteocytes and osteoclasts in vitro under physiologically relevant bone interstitial fluid flow shear stress. Our novel microfluidic co-culture platform provides an optimal tool for bone cell mechanistic studies and provides a platform for the discovery of potential drug targets for clinical treatments of bone-related diseases.

scholarly journals The Response of Corneal Endothelial Cells to Shear Stress in an In Vitro Flow Model

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Sujuan Duan ◽  
Yingjie Li ◽  
Yanyan Zhang ◽  
Xuan Zhu ◽  
Yan Mei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Flow ◽  
Corneal Endothelium ◽  
Aqueous Humour ◽  
Fluid Shear Stress ◽  
Corneal Endothelial Cells ◽  
Fluid Shear ◽  
Endothelial Cell Function

Purpose. Corneal endothelial cells are usually exposed to shear stress caused by the aqueous humour, which is similar to the exposure of vascular endothelial cells to shear stress caused by blood flow. However, the effect of fluid shear stress on corneal endothelial cells is still poorly understood. The purpose of this study was to explore whether the shear stress that results from the aqueous humour influences corneal endothelial cells. Methods. An in vitro model was established to generate fluid flow on cells, and the effect of fluid flow on corneal endothelial cells after exposure to two levels of shear stress for different durations was investigated. The mRNA and protein expression of corneal endothelium-related markers in rabbit corneal endothelial cells was evaluated by real-time PCR and western blotting. Results. The expression of the corneal endothelium-related markers ZO-1, N-cadherin, and Na+-K+-ATPase in rabbit corneal endothelial cells (RCECs) was upregulated at both the mRNA and protein levels after exposure to shear stress. Conclusion. This study demonstrates that RCECs respond favourably to fluid shear stress, which may contribute to the maintenance of corneal endothelial cell function. Furthermore, this study also provides a theoretical foundation for further investigating the response of human corneal endothelial cells to the shear stress caused by the aqueous humour.

Oscillatory Bone Fluid Flow and its Role in Initiating Remodeling in the Absence of Matrix Strain

2001 ◽  
Author(s):  
Yixian Qin ◽  
Anita Saldanha ◽  
Tamara Kaplan
Keyword(s):  
Fluid Flow ◽  
Cellular Response ◽  
Fluid Shear Stress ◽  
Bone Matrix ◽  
Fluid Pressure ◽  
Streaming Potential ◽  
Bone Adaptation ◽  
Interstitial Fluid Flow ◽  
Bone Fluid Flow ◽  
Matrix Deformation

Abstract Load-generated intracortical fluid flow is proposed to be an important mediator for regulating bone mass and morphology [1]. Although the mechanism of cellular response to induced flow parameters, i.e., fluid pressure, pressure gradient, velocity, and fluid shear stress, are not yet clear, interstitial fluid flow driven by loading may be necessary to explain the adaptive response of bone, which is either coupled with load-induced strain magnitude or independent with matrix strain per se [2]. It has been demonstrated that load-induced intracortical fluid flow is contributed by both bone matrix deformation and induced intramedullary (IM) pressure [3]. To examine the hypothesis of fluid flow generated adaptation, it is necessary to test the mechanism under the circumstances of solely fluid induced bone adaptation in the absence of matrix deformation. While our previous data has demonstrated that bone fluid flow and its associated streaming potential product can be influenced by the dynamic IM pressure quantitatively [4], the objective of this study was to evaluate fluid induced bone adaptation in an avian ulna model using oscillatory IM fluid pressure loading in the absence of bone matrix strain. The potential fluid pathway was measured in the model.

Fluid-Structure Interaction Modelling Predicts That Strain Transfer Through Focal Attachments of Osteoblast Cells are the Primary Mediators of Mechanical Stimulation Under Fluid Flow

2013 ◽  
Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara
Keyword(s):  
Fluid Flow ◽  
Mechanical Stimulation ◽  
Interstitial Fluid ◽  
Bone Cells ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Interaction Modelling

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. It has been proposed that indirect strain-induced flow of interstitial fluid surrounding bone cells may be the primary mediator of mechanical stimuli in-vivo [1]. Due to the practical difficulties in ascertaining whether interstitial fluid flow is indeed the primary mediator of mechanical stimuli in the in vivo environment, much of the evidence supporting this theory has been established through in vitro investigations that have observed cellular activity in response to fluid flow imposed by perfusion chambers [2]. While such in vitro experiments have identified key mechanisms involved in the mechanotransduction process, the exact mechanical stimulus being imparted to cells within a monolayer is unknown [3]. Furthermoreit is not clear whether the mechanical stimulation is comparable between different experimental systems or, more importantly, is representative of physiological loading conditions experienced by bone cells in vivo.

Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE2 but no change in mineralization

2001 ◽  
Vol 90 (5) ◽  
pp. 1849-1854 ◽  
Author(s):  
E. A. Nauman ◽  
R. L. Satcher ◽  
T. M. Keaveny ◽  
B. P. Halloran ◽  
D. D. Bikle
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Fluid Shear Stress ◽  
Bone Cells ◽  
Shear Stresses ◽  
Long Term Effects ◽  
Fluid Shear ◽  
Short Term

Although there is no consensus as to the precise nature of the mechanostimulatory signals imparted to the bone cells during remodeling, it has been postulated that deformation-induced fluid flow plays a role in the mechanotransduction pathway. In vitro, osteoblasts respond to fluid shear stress with an increase in PGE2production; however, the long-term effects of fluid shear stress on cell proliferation and differentiation have not been examined. The goal of this study was to apply continuous pulsatile fluid shear stresses to osteoblasts and determine whether the initial production of PGE2 is associated with long-term biochemical changes. The acute response of bone cells to a pulsatile fluid shear stress (0.6 ± 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold increase in PGE2 production. After 7 days of static culture (0 dyn/cm2) or low (0.06 ± 0.05 Pa, 0.3 Hz) or high (0.6 ± 0.5 Pa, 3.0 Hz) levels of pulsatile fluid shear stress, the bone cells responded with an 83% average increase in cell number, but no statistical difference ( P > 0.53) between the groups was observed. Alkaline phosphatase activity per cell decreased in the static cultures but not in the low- or high-flow groups. Mineralization was also unaffected by the different levels of applied shear stress. Our results indicate that short-term changes in PGE2 levels caused by pulsatile fluid flow are not associated with long-term changes in proliferation or mineralization of bone cells.

scholarly journals The collective influence of 1, 25-dihydroxyvitamin D3with physiological fluid shear stress on osteoblasts

2017 ◽  
Author(s):  
Yan Li ◽  
Jiafeng Yuan ◽  
Qianwen Wang ◽  
Lijie Sun ◽  
Yunying Sha ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Mechanical Stimuli ◽  
Fluid Shear ◽  
Dihydroxyvitamin D ◽  
Physiological Fluid ◽  
Flow Shear Stress ◽  
System 1 ◽  
Collective Influence

Abstract1, 25-dihydroxyvitamin D3(1, 25 (OH)2D3) and mechanical stimuli in physiological environment play an important role in the pathogenesis of osteoporosis. The effects of 1, 25-dihydroxyvitamin D3alone and mechanical stimuli alone on osteoblasts have been widely investigated. This study reports the collective influences of 1, 25-dihydroxyvitamin D3and flow shear stress (FSS) on biological functions of osteoblasts. 1, 25 (OH)2D3were constructed in various kinds of concentration (0, 1, 10, 100 nmmol/L), while physiological fluid shear stress (12 dynes/cm2) were produced by using a parallel-plate fluid flow system. 1, 25 (OH)2D3affects the responses of ROBs to FSS, including the inhibition of NO releases and cell proliferation as well as the promotion of PGE2releases and cell differentiation. These findings provide a possible mechanism by which 1, 25(OH)2D3influences osteoblasts responses to FSS and may provide guidance for the selection of 1, 25(OH)2D3concentration and mechanical loading in order toin vitroproduce functional bone tissues.

scholarly journals Rapid Fabrication of Microfluidic Devices for Biological Mimicking: A Survey of Materials and Biocompatibility

Micromachines ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 346
Author(s):  
Hui Ling Ma ◽  
Ana Carolina Urbaczek ◽  
Fayene Zeferino Ribeiro de Souza ◽  
Paulo Augusto Gomes Garrido Carneiro Leão ◽  
Janice Rodrigues Perussi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cell Viability ◽  
Cellular Response ◽  
Fluid Shear Stress ◽  
Umbilical Vein ◽  
Microfluidic Devices ◽  
In Vitro Assays ◽  
Stress Effect

Microfluidics is an essential technique used in the development of in vitro models for mimicking complex biological systems. The microchip with microfluidic flows offers the precise control of the microenvironment where the cells can grow and structure inside channels to resemble in vivo conditions allowing a proper cellular response investigation. Hence, this study aimed to develop low-cost, simple microchips to simulate the shear stress effect on the human umbilical vein endothelial cells (HUVEC). Differentially from other biological microfluidic devices described in the literature, we used readily available tools like heat-lamination, toner printer, laser cutter and biocompatible double-sided adhesive tapes to bind different layers of materials together, forming a designed composite with a microchannel. In addition, we screened alternative substrates, including polyester-toner, polyester-vinyl, glass, Permanox® and polystyrene to compose the microchips for optimizing cell adhesion, then enabling these microdevices when coupled to a syringe pump, the cells can withstand the fluid shear stress range from 1 to 4 dyne cm2. The cell viability was monitored by acridine orange/ethidium bromide (AO/EB) staining to detect live and dead cells. As a result, our fabrication processes were cost-effective and straightforward. The materials investigated in the assembling of the microchips exhibited good cell viability and biocompatibility, providing a dynamic microenvironment for cell proliferation. Therefore, we suggest that these microchips could be available everywhere, allowing in vitro assays for daily laboratory experiments and further developing the organ-on-a-chip concept.

scholarly journals Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 765
Author(s):  
Qianbin Zhao ◽  
Tim Cole ◽  
Yuxin Zhang ◽  
Shi-Yang Tang
Keyword(s):  
Cell Culture ◽  
Shear Stress ◽  
Cultured Cells ◽  
Mechanical Strain ◽  
3D Cell Culture ◽  
Small Scale ◽  
Mechanical Stimuli ◽  
Human Organ ◽  
Organ On A Chip

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.

scholarly journals Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

1986 ◽  
Vol 83 (7) ◽  
pp. 2114-2117 ◽  
Author(s):  
P. F. Davies ◽  
A. Remuzzi ◽  
E. J. Gordon ◽  
C. F. Dewey ◽  
M. A. Gimbrone
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Cell Turnover ◽  
Fluid Shear ◽  
Turbulent Fluid
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