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.

scholarly journals Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

2021 ◽  
Author(s):  
Barbara Bachmann ◽  
Sarah Spitz ◽  
Christian Jordan ◽  
Patrick Schuller ◽  
Heinz D Wanzenboeck ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Scientific Progress ◽  
Morphological Characteristics ◽  
Interstitial Fluid Flow

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulation's importance on lymphatic sprout formation. Our microvascular model's key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

scholarly journals A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

2013 ◽  
Vol 10 (81) ◽  
pp. 20120900 ◽  
Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Parallel Plate ◽  
Bone Cells ◽  
Mechanical Stimulus ◽  
Flow Chamber ◽  
Parallel Plate Flow Chamber ◽  
Structure Interaction

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment and strain-induced flow of interstitial fluid is believed to be the primary mediator of mechanical stimuli to bone cells in vivo. In vitro investigations have shown that bone cells produce important biochemical signals in response to fluid flow applied using parallel-plate flow chamber (PPFC) systems. However, the exact mechanical stimulus experienced by the cells within these systems remains unclear. To fully understand this behaviour represents a most challenging multi-physics problem involving the interaction between deformable cellular structures and adjacent fluid flows. In this study, we use a fluid–structure interaction computational approach to investigate the nature of the mechanical stimulus being applied to a single osteoblast cell under fluid flow within a PPFC system. The analysis decouples the contribution of pressure and shear stress on cellular deformation and for the first time highlights that cell strain under flow is dominated by the pressure in the PPFC system rather than the applied shear stress. Furthermore, it was found that strains imparted on the cell membrane were relatively low whereas significant strain amplification occurred at the cell–substrate interface. These results suggest that strain transfer through focal attachments at the base of the cell are the primary mediators of mechanical signals to the cell under flow in a PPFC system. Such information is vital in order to correctly interpret biological responses of bone cells under in vitro stimulation and elucidate the mechanisms associated with mechanotransduction in vivo .

Loading-Induced Interstitial Fluid Flow in Bone Mechanobiology: An FSI Approach to the Osteocyte Environment

2012 ◽  
Author(s):  
Stefaan W. Verbruggen ◽  
Ted J. Vaughan ◽  
Laoise M. McNamara
Keyword(s):  
Adaptive Response ◽  
Interstitial Fluid ◽  
Bone Growth ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Physiological Demands ◽  
Control Bone ◽  
Ubiquitous Presence

Bone is an adaptive material, which is particularly responsive to mechanical loading and can adapt its mass and structure to meet the mechanical demands experienced throughout life. The osteocyte, due to its ubiquitous presence throughout bone, is believed to act as the main sensor of mechanical stimulus in bone, recruiting other cells to control bone growth and resorption in response to changes in physiological demands. However the precise mechanical stimuli that osteocytes experience in vivo, and what type of stimulus instigates an adaptive response, are not fully understood.

Gap Junctions and Osteoblast-like Cell Gene Expression in Response to Fluid Flow

2008 ◽  
Vol 131 (1) ◽  
Author(s):  
Michael G. Jekir ◽  
Henry J. Donahue
Keyword(s):  
Fluid Flow ◽  
Gap Junctions ◽  
Gap Junction ◽  
Bone Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Mechanical Stimuli ◽  
Junctional Communication ◽  
Osteogenic Response

Bone formation occurs in vivo in response to mechanical stimuli, but the signaling pathways involved remain unclear. The ability of bone cells to communicate with each other in the presence of an applied load may influence the overall osteogenic response. The goal of this research was to determine whether inhibiting cell-to-cell gap junctional communication between bone-forming cells would affect the ensemble cell response to an applied mechanical stimulus in vitro. In this study, we investigated the effects of controlled oscillatory fluid flow (OFF) on osteoblastic cells in the presence and the absence of a gap-junction blocker. MC3T3-E1 Clone 14 cells in a monolayer were exposed to 2h of OFF at a rate sufficient to create a shear stress of 20dynes∕cm2 at the cell surface, and changes in steady-state mRNA levels for a number of key proteins known to be involved in osteogenesis were measured. Of the five proteins investigated, mRNA levels for osteopontin (OPN) and osteocalcin were found to be significantly increased 24h postflow. These experiments were repeated in the presence of 18β-glycyrrhetinic acid (BGA), a known gap-junction blocker, to determine whether gap-junction intercellular communication is necessary for this response. We found that the increase in OPN mRNA levels is not observed in the presence of BGA, suggesting that gap junctions are involved in the signaling process. Interestingly, enzyme linked immunosorbent assay data showed that levels of secreted OPN protein increased 48h postflow and that this increase was unaffected by the presence of intact gap junctions.

scholarly journals TAMI-15. THE EFFECT OF INTERSTITIAL FLUID FLOW AND ASTROCYTES / MICROGLIA ON INVASION, PROLIFERATION AND STEMNESS OF PATIENT-DERIVED GLIOMA STEM CELLS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii216-ii216
Author(s):  
Naciye Atay ◽  
Jessica Yuan ◽  
Chase Cornelison ◽  
Jennifer Munson
Keyword(s):  
Stem Cells ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Pressure Head ◽  
Molecular Classification ◽  
Patient Specific ◽  
Glioma Stem Cells ◽  
Interstitial Fluid Flow ◽  
Static Conditions

Abstract SIGNIFICANCE Glioblastoma is a highly infiltrative, malignant, and deadly glioma that can be classified into subtypes based on molecular classification. Treatment resistant glioma stem cells (GSCs) depend on the tumor microenvironment (TME) to drive recurrence. Cellular composition and interstitial fluid flow (IFF) are significant aspects of the TME. IFF and astrocyte and microglia (A+M) presence have independently been shown to mediate invasion. This study’s goal is to expand our knowledge of IFF and A+M effects on invasion to proliferation and stemness. METHODS Seven patient-derived GSC lines were tested in an in vitro 3D model, which consists of GSCs ± A+M resuspended in 0.2% hyaluronan / 0.12% rat tail collagen I gel. The gel was applied to an 8um pore 96-well transwell system. Flow and static conditions were modeled with and without a pressure head above the gel, respectively. Cells beyond the transwell membrane after 18 hrs of incubation were considered invaded. Stemness and proliferation were determined via flow cytometry for CD71 and Ki67, respectively. RESULTS/CONCLUSIONS The three mesenchymal GSC lines tested exhibited the largest IFF fold increases in stemness, proliferation, and invasion with averages of 23.9, 19.1, and 2.1, respectively. CD44+ cell populations, highest in mesenchymal cells, had a strong correlation with proliferation (R=0.8439) and stemness (R=0.7829) under flow. Furthermore, depending on the cell line/subtype, the addition of A+M either amplified, reduced, reversed, mitigated, or kept constant the effect of IFF on invasion and proliferation. Incorporating A+M never amplified the effect of IFF on stemness. Adding A+M had a strong effect on the IFF fold change of at least one parameter in six of the cell lines. This is the first presentation showing that IFF, patient-specific, and context-specific factors contribute to both increased proliferation, and maintenance of stem-like phenotypes in glioma.

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.

Direct Hydraulic Permeability Measurements of Agarose Hydrogels Used as Cell Scaffolds

1999 ◽  
Author(s):  
Michael A. Soltz ◽  
Anna Stankiewicz ◽  
Gerard Ateshian ◽  
Robert L. Mauck ◽  
Clark T. Hung
Keyword(s):  
Fluid Flow ◽  
Articular Cartilage ◽  
Interstitial Fluid ◽  
Convective Transport ◽  
Hydraulic Permeability ◽  
Interstitial Fluid Flow ◽  
Pass Through ◽  
Fluid Pressurization ◽  
First Time

Abstract The objective of this study was to determine the intrinsic hydraulic permeability of 2% agarose hydrogels. Two-percent agarose was chosen because it is a concentration typically used for encapsulation of chondrocytes in suspension cultures [3–5], Hydraulic permeability is a measure of the relative ease by which fluid can pass through a material. Importantly, it governs the level of interstitial fluid flow as well as the interstitial fluid pressurization that is generated in a material during loading. Fluid pressurization is the source of the unique load-bearing and lubrication properties of articular cartilage [1,17] and represents a major component of the in vivo chondrocyte environment. We have previously reported that 2% agarose hydrogels can support fluid pressurization, albeit to a significantly lesser degree than articular cartilage [18]. Interstitial fluid flow gives rise to convective transport of nutrients and ions [6,7] and matrix compaction [9] which may serve as important stimuli to chondrocytes. We report for the first time the strain-dependent hydraulic permeability of 2% agarose hydrogels.

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.

Sign in / Sign up

Export Citation Format

Share Document