scholarly journals Multilayer microfluidic platform for the study of luminal, transmural, and interstitial flow

2022 ◽  
Author(s):  
Gi-hun Lee ◽  
Stephanie A Huang ◽  
Wen Yih Aw ◽  
Mitesh Rathod ◽  
Crescentia Cho ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Fluid Velocity ◽  
Expression Patterns ◽  
Fluid Pressure ◽  
Solid Cancer ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Flowing Fluid ◽  
Microfluidic Platform ◽  
Gene And Protein Expression

Abstract Efficient delivery of oxygen and nutrients to tissues requires an intricate balance of blood, lymphatic, and interstitial fluid pressures, and gradients in fluid pressure drive the flow of blood, lymph, and interstitial fluid through tissues. While specific fluid mechanical stimuli, such as wall shear stress, have been shown to modulate cellular signaling pathways along with gene and protein expression patterns, an understanding of the key signals imparted by flowing fluid and how these signals are integrated across multiple cells and cell types in native tissues is incomplete due to limitations with current assays. Here, we introduce a multi-layer microfluidic platform (MLTI-Flow) that enables the culture of engineered blood and lymphatic microvessels and independent control of blood, lymphatic, and interstitial fluid pressures. Using optical microscopy methods to measure fluid velocity for applied input pressures, we demonstrate varying rates of interstitial fluid flow as a function of blood, lymphatic, and interstitial pressure, consistent with computational fluid dynamics models. The resulting microfluidic and computational platforms will provide for analysis of key fluid mechanical parameters and cellular mechanisms that contribute to diseases in which fluid imbalances play a role in progression, including lymphedema and solid cancer.

Anabolic Fluid Flow as Dependent on It Dose and Frequency in Bone Formation and Inhibition of Bone Loss

2004 ◽  
Author(s):  
Yi-Xian Qin ◽  
Tamara Kaplan ◽  
Hoyan Lam
Keyword(s):  
Fluid Flow ◽  
Adaptive Response ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Bone Adaptation ◽  
Fluid Loading ◽  
Interstitial Fluid Flow ◽  
Flow Rates ◽  
Dynamic Components ◽  
One Year

Anabolic response of bone to interstitial fluid flow is strongly dependent on the dynamic components of the fluid pressure, implying that fluid flow is a critical regulatory component to bone mass and morphology. While the fluid stimulus can be potentially applied for therapeutic in promoting turnover, the hypothesis of fluid induced bone adaptation was evaluated in an avian ulna model using varied flow rates and magnitudes. Total of 12 one-year old male avian animals was used in this study. A sinusoidal fluid pressure was applied to the experimental ulna 10 min/day for 4 weeks. Three experimental groups of loading were performed at 1 and 30 Hz of fluid loading. The results reveal an increase of 22.7%±7.2 in trabecular volume for group of 30 Hz, 76mmHg loading, while it had only 0.5 % increase at 1Hz, 76 mmHg loading. Under physiologic fluid pressure, a higher flow rate of stimuli generates much higher remodeling response than a lower rate of loading. This implies that bone turnover may be sensitive to the dynamic components of fluid flow, thereby initiating the adaptive response.

scholarly journals The Mechanical Microenvironment in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1452
Author(s):  
Stephen J.P. Pratt ◽  
Rachel M. Lee ◽  
Stuart S. Martin
Keyword(s):  
Breast Cancer ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Normal Breast ◽  
Interstitial Fluid Pressure ◽  
Mechanical Stimuli ◽  
Solid Stress ◽  
Physical Cues

Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

scholarly journals Effects of pulsating heat source on interstitial fluid transport in tumour tissues

2020 ◽  
Vol 17 (170) ◽  
pp. 20200612
Author(s):  
A. Andreozzi ◽  
M. Iasiello ◽  
P. A. Netti
Keyword(s):  
Drug Delivery ◽  
Interstitial Fluid ◽  
Fluid Transport ◽  
Solid Phase ◽  
Fluid Velocity ◽  
Fluid Pressure ◽  
Volumetric Strain ◽  
Current Approach ◽  
Solid Matrix ◽  
Mass Source

Macromolecules and drug delivery to solid tumours is strongly influenced by fluid flow through interstitium, and pressure-induced tissue deformations can have a role in this. Recently, it has been shown that temperature-induced tissue deformation can influence interstitial fluid velocity and pressure fields, too. In this paper, the effect of modulating-heat strategies to influence interstitial fluid transport in tissues is analysed. The whole tumour tissue is modelled as a deformable porous material, where the solid phase is made up of the extracellular matrix and cells, while the fluid phase is the interstitial fluid that moves through the solid matrix driven by the fluid pressure gradient and vascular capillaries that are modelled as a uniformly interspersed fluid point-source. Pulsating-heat generation is modelled with a time-variable cosine function starting from a direct current approach to solve the voltage equation, for different pulsations. From the steady-state solution, a step-variation of vascular pressure included in the model equation as a mass source term via the Starling equation is simulated. Dimensionless 1D radial equations are numerically solved with a finite-element scheme. Results are presented in terms of temperature, volumetric strain, pressure and velocity profiles under different conditions. It is shown that a modulating-heat procedure influences velocity fields, that might have a consequence in terms of mass transport for macromolecules or drug delivery.

Dynamics of Calcium Signal and Leukotriene C4Release in Mast Cells Network Induced by Mechanical Stimuli and Modulated by Interstitial Fluid Flow

2015 ◽  
Vol 8 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Wei Yao ◽  
Hongwei Yang ◽  
Yabei Li ◽  
Guanghong Ding
Keyword(s):  
Fluid Flow ◽  
Mast Cells ◽  
Intracellular Calcium ◽  
Signaling Pathways ◽  
Interstitial Fluid ◽  
Calcium Signal ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Crac Channels ◽  
Intracellular Ca

AbstractMast cells (MCs) play an important role in the immune system. Through connective tissues, mechanical stimuli activate intracellular calcium signaling pathways, induce a variety of mediators including leukotriene C4(LTC4) release, and affect MCs’ microenvironment. This paper focuses on MCs’ intracellular calcium dynamics and LTC4release responding to mechanical stimuli, explores signaling pathways in MCs and the effect of interstitial fluid flow on the transport of biological messengers and feedback in the MCs network. We use a mathematical model to show that (i) mechanical stimuli including shear stress induced by interstitial fluid flow can activate mechano-sensitive (MS) ion channels on MCs’ membrane and allow Ca2+entry, which increases intracellular Ca2+concentration and leads to LTC4release; (ii) LTC4in the extracellular space (ECS) acts on surface cysteinyl leukotriene receptors (LTC4R) on adjacent cells, leading to Ca2+influx through Ca2+release-activated Ca2+(CRAC) channels. An elevated intracellular Ca2+concentration further stimulates LTC4release and creates a positive feedback in the MCs network. The findings of this study may facilitate our understanding of the mechanotransduction process in MCs induced by mechanical stimuli, contribute to understanding of interstitial flow-related mechanobiology in MCs network, and provide a methodology for quantitatively analyzing physical treatment methods including acupuncture and massage in traditional Chinese medicine (TCM).

Cyclic Strain and Interstitial Flow Modulate Cardiac Fibroblast Phenotype Through Angiotensin II and TGF-β Pathways

2011 ◽  
Author(s):  
Peter A. Galie ◽  
Jan P. Stegemann
Keyword(s):  
Interstitial Fluid ◽  
Cardiac Fibroblasts ◽  
Cyclic Strain ◽  
Mechanical Stimuli ◽  
Interstitial Flow ◽  
Interstitial Fluid Flow ◽  
Matrix Deposition ◽  
Myofibroblast Phenotype ◽  
Fibrotic Scar ◽  
Extracellular Matrix Deposition

A fibrotic scar in the myocardium is characterized by excessive extracellular matrix deposition, loss of functioning cardiomyocytes, and the transition of healthy cardiac fibroblasts to a myofibroblast phenotype. Previous research has suggested that the myofibroblast transition is mediated by mechanical stimuli including cyclic strain [1–2] and interstitial fluid flow [3–5].

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.

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.

Control of interstitial fluid pressure: Role of [beta ]-integrins

2001 ◽  
Vol 21 (3) ◽  
pp. 222-230 ◽  
Author(s):  
Rolf K. Reed ◽  
Ansgar Berg ◽  
Eli-Anne B. Gjerde ◽  
Kristofer Rubin
Keyword(s):  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure
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