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The objective of this study is to take an initial step to determine and interpret the extents to which biophysical wound dressing properties impact mechanotransduction within a wound tissue. Current experimental techniques make it challenging to investigate many of the complexities of the wound healing process. Thus, the purpose of this study is to begin with computational models and theoretical descriptions that propose predictions and explanations of the role of various mechanical wound dressing characteristics on mechanotransduction in wound tissues. Three‐dimensional models of wound tissue and wound dressings have been developed to analyze how von Mises stresses are distributed within the tissue models. Our results show that shorter ellipsoid dressings lead to highest stresses within the wound tissue where dressing's thickness and stiffness don't show a significant impact. When using a rectangular dressing, shorter, softer, thinner ones lead to high stress transmission to a wound tissue. [ABSTRACT FROM AUTHOR]

Chronic wounds are significant public health problems impacting the health-related quality of individuals' lives (due to disability, decreased productivity, and loss of independence) and an immense economic burden to healthcare systems around the world. In this study, our main objective is to investigate how mechanotransduction can impact the healing process in chronic wounds. We have developed new three-dimensional models of wound tissue to study the distribution of forces within these tissues exerted by wound dressings with different characteristics. The roles of mechanical forces on wound healing have gained significant clinical attention; the application of mechanical forces is expected to influence the physiology of tissue surrounding a wound. We aim to investigate whether the force transmission within wound tissue is impacted by the dressing characteristics and whether this impact may differ with wound tissue's properties. Our results show that wound dressings with lower stiffnesses promote force transmission within a wound tissue. This impact is even more significant on stiffer wound tissues. Furthermore, we show that size of wound dressing alters forces that transmit within the wound tissue where dressings with 9 cm length show higher stresses. The wound tissue stiffening has been associated with healing of a wound. Our results demonstrate that wounds with stiffer tissue experience higher stresses. Taken all together, our findings suggest that low stiffness of wound dressing and its size may be introduced as a criterion to explain parameters predisposing a chronic wound to heal. This study's findings on the role of dressings and tissue characteristics demonstrate that precision dressings are required for wound management and understanding how a dressing impacts mechanotransduction in wound tissue will lead to design of novel dressings promoting healing in chronic wounds. [ABSTRACT FROM AUTHOR]

A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the influences of increased endothelial cell turnover and deformation of the intima at higher pressure. Meanwhile, the thickness and properties of the endothelium, intima, internal elastic lamina (IEL), and media are affected by the transmural pressure. The LDL macromolecules enter the intima through leaky junctions over the endothelium, which are created by dying or dividing cells. Water molecules enter the intima via the paracellular pathway through breaks in tight junctions after passing the glycocalyx as well as through leaky junctions. The glycocalyx is modeled as a Brinkman porous medium to describe the fluid filtration associated with its structure. Combined Navier-Stokes and Brinkman equations are solved for the transmural flow, and the convective-diffusion equation is employed for LDL transport. The permeation of LDL over the surface of smooth muscle cells is modeled through a uniform reaction evenly distributed in the macroscopically homogeneous media layer. Simulations are performed in an axisymmetric plane centered at a leaky cell. The overriding issue addressed is that LDL fluxes across the leaky junction, the intima, fenestral pores in the IEL, and the media layer are highly affected by the transmural pressure, which affects the endothelial cell turnover rate and the compaction of intima. The present model, for the first time and with no adjustable parameters, is capable of making many realistic predictions including the proper magnitudes for the permeability of endothelium and intimal layers and the hydraulic conductivity of all layers as well as their trends with pressure. Results for the volume flux through the wall and the hydraulic conductivity of the entire arterial wall, the endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement with previous experimental studies. lipoprotein transport; computational fluid dynamics; convection-diffusion model; atherosclerosis

Hypertension and cancer are two of the leading global causes of death. Hypertension, known as chronic high blood pressure, affects approximately 45% of the American population and is a growing condition in other parts of the world, particularly in Asia and Europe. On the other hand, cancer resulted in approximately 10 million deaths in 2020 worldwide. Several studies indicate a coexistence of these two conditions, specifically that hypertension, independently, is associated with an increased risk of cancer. In the present study, we conducted a meta-analysis initially to reveal the prevalence of hypertension and cancer comorbidity and then to assess which organ-specific cancers were associated with hypertension by calculating the summary relative risks (RRs) and 95% confidence intervals (CIs). Our analysis shows that hypertension plays a role in cancer initiation. Our extended analysis on how the hypertension-associated angiogenesis factors are linked to cancer demonstrated that matrix metalloproteinases 2 and 9 appear to be two key factors facilitating cancer in hypertensive patients. This work serves as an important step in the current assessment of hypertension-promoted increased risk of 19 different cancers, particularly kidney, renal cell carcinoma, breast, colorectal, endometrial, and bladder. These findings provide new insight into how to treat and prevent cancer in hypertensive patients. [ABSTRACT FROM AUTHOR]

Endothelial surface layer (glycocalyx) is the major physiological regulator of tumor cell adhesion to endothelium. Cancer cells express vascular endothelial growth factor (VEGF) which increases the permeability of a microvessel wall by degrading glycocalyx. Endothelial cells lining large arteries have also been reported, in vitro and in vivo, to mediate VEGF expression significantly under exposure to high wall shear stress (WSS) > 0.6 Pa. The objective of the present study is to explore whether local hemodynamic conditions in the vicinity of a migrating deformable cancer cell can influence the function of endothelial cells to express VEGF within the microvasculature. A three-dimensional model of deformable cancer cells (DCCs) migrating within a capillary is developed by applying a massively parallel hemodynamics application to simulate the fluid-structure interaction between the DCC and fluid surrounding the DCC. We study how dynamic interactions between the DCC and its local microenvironment affect WSS exposed on endothelium, under physiological conditions of capillaries with different diameters and flow conditions. Moreover, we quantify the area of endothelium affected by the DCC. Our results show that the DCC alters local hemodynamics in its vicinity up to an area as large as 40 times the cancer cell lateral surface. In this area, endothelium experiences high WSS values in the range of 0.6–12 Pa. Endothelial cells exposed to this range of WSS have been reported to express VEGF. Furthermore, we demonstrate that stiffer cancer cells expose higher WSS on the endothelium. A strong impact of cell stiffness on its local microenvironment is observed in capillaries with diameters <16 μm. WSS-induced-VEGF by endothelium represents an important potential mechanism for cancer cell adhesion and metastasis in the microvasculature. This work serves as an important first step in understanding the mechanisms driving VEGF-expression by endothelium and identifying the underlying mechanisms of glycocalyx degradation by endothelium in microvasculature. The identification of angiogenesis factors involved in early stages of cancer cell-endothelium interactions and understanding their regulation will help, first to develop anti-angiogenic strategies applied to diagnostic studies and therapeutic interventions, second to predict accurately where different cancer cell types most likely adhere in microvasculature, and third to establish accurate criteria predisposing the cancer metastasis. [ABSTRACT FROM AUTHOR]

Morphological and hemodynamic parameters have been suggested to affect the rupture of cerebral aneurysms, but detailed mechanisms of rupture are poorly understood. The purpose of our study is to determine criteria for predicting the risk of aneurysm rupture, which is critical for improved patient management. Existing aneurysm hemodynamics studies generally evaluate limited geometries or Reynolds numbers (Re), which are difficult to apply to a wide range of patient‐specific cases. Association between hemodynamic characteristics and morphology is focused. Several two‐dimensional (2D) and three‐dimensional (3D) idealized and physiological geometries is assessed to characterize the hemodynamic landscape between flow patterns. The impact of morphology on velocity and wall shear stress (WSS) profiles were evaluated. Slight changes in aneurysm geometry is found or Re result in significant changes in the hemodynamic and WSS profiles. Our systematic mapping and nondimensional analysis qualitatively identify hemodynamic conditions that may predispose aneurysms to rupture. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2792–2802, 2018 [ABSTRACT FROM AUTHOR]

The current study presents computational models to investigate the poststenting hemodynamic stresses and internal stresses over/within the diseased walls of coronary arteries which are in different states of atherosclerotic plaque. The finite element method is applied to build the axisymmetric models which include the plaque, arterial wall, and stent struts. The study takes into account the mechanical effects of the opening pressure and its association with the plaque severity and the morphology. The wall shear stresses and the von Mises stresses within the stented coronary arteries show their strong dependence on the plaque structure, particularly the fibrous cap thickness. Higher stresses occur in severely stenosed coronaries with a thinner fibrous cap. Large stress concentrations around the stent struts cause injury or damage to the vessel wall which is linked to the mechanism of restenosis. The in-stent restenosis rate is also highly dependent on the opening pressure, to the extent that stenosed artery is expanded, and geometry of the stent struts. The present study demonstrates, for the first time, that the restenosis is to be viewed as a consequence of biomechanical design of a stent repeating unit, the opening pressure, and the severity and morphology of the plaque. [ABSTRACT FROM AUTHOR]

Histological images from the longitudinal section of four diseased coronary arteries were used, for the first time, to study the pulsatile blood flow distribution within the lumen of the arteries bymeans of computational fluid dynamics (CFD). Results indicate a strong dependence of the hemodynamics on the morphology of atherosclerotic lesion. Distinctive flowpatterns appear in different stenosed regions corresponding to the specific geometry of any artery. Results show that the stenosis affects the wall shear stress (WSS) locally along the diseased arterial wall as well as other adjacent walls. The maximum magnitude of WSS is observed in the throat of stenosis. Moreover, high oscillatory shear index (OSI) is observed along the stenosed wall and the high curvature regions. The present study is capable of providing information on the shear environment in the longitudinal section of the diseased coronary arteries, based on the models created from histological images. The computational method may be used as an effective way to predict plaque forming regions in healthy arterial walls. [ABSTRACT FROM AUTHOR]

A three-dimensional computer model of human aortic arch with three branches is reproduced to study the pulsatile blood flow with Finite Element Method. In specific, the focus is on variation of wall shear stress, which plays an important role in the localization and development of atherosclerotic plaques. Pulsatile pressure pulse is used as boundary condition to avoid flow entry development, and the aorta walls are considered rigid. The aorta model along with boundary conditions is altered to study the effect of hypotension and hypertension. The results illustrated low and fluctuating shear stress at outer and inner wall of aortic arch, proximal wall of branches, and entry region. Despite the simplification of aorta model, rigid walls and other assumptions results displayed that hypertension causes lowered local wall shear stresses. It is the sign of an increased risk of atherosclerosis. The assessment of hemodynamics shows that under the flow regimes of hypotension and hypertension, the risk of atherosclerosis localization in human aorta may increase. [ABSTRACT FROM AUTHOR]

Purpose . This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives. Methods . This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances. Results . This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review. Conclusion . Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Mechanical force exerted on cancer cells by their microenvironment have been reported to drive cells toward invasive phenotypes by altering cells' motility, proliferation, and apoptosis. These mechanical forces include compressive, tensile, hydrostatic, and shear forces. The importance of forces is then hypothesized to be an alteration of cancer cells' and their microenvironment's biophysical properties as the indicator of a tumor's malignancy state. Our objective is to investigate and quantify the correlation between a tumor's malignancy state and forces experienced by the cancer cells and components of the microenvironment. In this study, we have developed a multicomponent, three-dimensional model of tumor tissue consisting of a cancer cell surrounded by fibroblasts and extracellular matrix (ECM). Our results on three different organs including breast, kidney, and pancreas show that: A) the stresses within tumor tissue are impacted by the organ specific ECM's biophysical properties, B) more invasive cancer cells experience higher stresses, C) in pancreas which has a softer ECM (Young modulus of 1.0 kPa) and stiffer cancer cells (Young modulus of 2.4 kPa and 1.7 kPa) than breast and kidney, cancer cells experienced significantly higher stresses, D) cancer cells in contact with ECM experienced higher stresses compared to cells surrounded by fibroblasts but the area of tumor stroma experiencing high stresses has a maximum length of 40 μm when the cancer cell is surrounded by fibroblasts and 12 μm for when the cancer cell is in vicinity of ECM. This study serves as an important first step in understanding of how the stresses experienced by cancer cells, fibroblasts, and ECM are associated with malignancy states of cancer cells in different organs. The quantification of forces exerted on cancer cells by different organ-specific ECM and at different stages of malignancy will help, first to develop theranostic strategies, second to predict accurately which tumors will become highly malignant, and third to establish accurate criteria controlling the progression of cancer cells malignancy. Furthermore, our in silico model of tumor tissue can yield critical, useful information for guiding ex vivo or in vitro experiments, narrowing down variables to be investigated, understanding what factors could be impacting cancer treatments or even biomarkers to be looking for., Competing Interests: The authors declares that they have no financial, professional, or personal conflict of interest., (© 2024 The Authors.)

Background: As indications for flow diversion (FD) have expanded, new challenges in deployment of flow diverting devices (FDDs) have been encountered. We present 4 cases with aneurysms in which deployment of FDDs were complicated by device malapposition and compromised opening in regions of parent vessel stenosis. In all 4 cases, a balloon-mounted stent was ultimately deployed within the FDD., Objective: To describe the use of balloon-mounted stents (BMS) within FDDs for correction of flow-limiting stenosis and device malapposition., Methods: Patients undergoing FD for treatment of aneurysms complicated by refractory flow-limiting stenosis were identified through multi-center retrospective review. Those cases requiring use of BMS were identified. Further investigation in one of the cases was performed with a simulated pulsatile blood flow model., Results: After attempts to perform balloon angioplasty proved unsuccessful, BMS deployment successfully opened the stenotic parent artery and improved FDD wall apposition in all 4 cases. Simulated pulsatile blood flow modeling confirmed improvements in the distribution of velocity, wall shear stress, oscillatory shear index, and flow pattern structure after stent deployment. One case was complicated by asymptomatic in-stent thrombosis., Conclusion: In cases of FDD deployment complicated by flow-limiting stenosis refractory to conventional techniques, a BMS deployed within the FD can provide radial support to open both the stenotic device and parent artery. Resulting improvements in device wall apposition may portend greater long-term efficacy of FD. In-stent occlusion can occur and may reflect a thrombogenic interaction between the devices., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction., (© 2017 The Author(s).)

Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm(-2). Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.6° in an EC monolayer, which is somewhat below the measured value (9.9°) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)