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Experiments on tumor spheroids have shown that compressive stress from their environment can reversibly decrease tumor expansion rates and final sizes. Stress release experiments show that nonuniform anisotropic elastic stresses can be distributed throughout. The elastic stresses are maintained by structural proteins and adhesive molecules, and can be actively relaxed by a variety of biophysical processes. In this paper, we present a new continuum model to investigate how the growth-induced elastic stresses and active stress relaxation, in conjunction with cell size control feedback machinery, regulate the cell density and stress distributions within growing tumors as well as the tumor sizes in the presence of external physical confinement and gradients of growth-promoting chemical fields. We introduce an adaptive reference map that relates the current position with the reference position but adapts to the current position in the Eulerian frame (lab coordinates) via relaxation. This type of stress relaxation is similar to but simpler than the classical Maxwell model of viscoelasticity in its formulation. By fitting the model to experimental data from two independent studies of tumor spheroid growth and their cell density distributions, treating the tumors as incompressible, neo-Hookean elastic materials, we find that the rates of stress relaxation of tumor tissues can be comparable to volumetric growth rates. Our study provides insight on how the biophysical properties of the tumor and host microenvironment, mechanical feedback control and diffusion-limited differential growth act in concert to regulate spatial patterns of stress and growth. When the tumor is stiffer than the host, our model predicts tumors are more able to change their size and mechanical state autonomously, which may help to explain why increased tumor stiffness is an established hallmark of malignant tumors., Author summary The mechanical state of cells can modulate their growth and division dynamics via mechanotransduction, which affects both the cell size distribution and the tissue size as a whole. Experiments on tumor spheroids have shown that compressive stress from their environment can reversibly decrease tumor expansion rates and final sizes. Besides external confinement and compression on the tumor border, a heterogeneous stress field can be generated inside the tumor by nutrient-driven differential growth. Such growth-induced mechanical stresses can be relaxed by tissue rearrangement, which happens during cell neighbor exchanges, cell divisions, and extracellular matrix renewal. In this study, we have developed a continuum model that describes the above mechanical interactions and the dynamics of tissue rearrangement explicitly. Motivated by published experimental data, we consider mechanotransduction where the local compressive stress slows down cell growth and cell size reduction limits cell division. We have analyzed how external mechanical stimuli and internal processes influence the outcome of cell-and-tissue sizes and spatial patterns of cell density and mechanical stress in growing tumors.

Hydraulic fracturing of unconventional reservoirs has seen a boom in the last century, as a means to fulfill the growing energy demand in the world. The fracturing fluid used in the process plays a substantial role in determining the results. Hence, several research and development efforts have been geared towards developing more sustainable, efficient, and improved fracturing fluids. Herein, we present a dynamic binary complex (DBC) solution, with potential to be useful in the hydraulic fracturing domain. It has a supramolecular structure formed by the self-assembly of low molecular weight viscosifiers (LMWVs) oleic acid and diethylenetriamine into an elongated entangled network under alkaline conditions. With less than 2 wt% constituents dispersed in aqueous solution, a viscous gel that exhibits high viscosities even under shear was formed. Key features include responsiveness to pH and salinity, and a zero-shear viscosity that could be tuned by a factor of ~280 by changing the pH. Furthermore, its viscous properties were more pronounced in the presence of salt. Sand settling tests revealed its potential to hold up sand particles for extended periods of time. In conclusion, this DBC solution system has potential to be utilized as a smart salt-responsive, pH-switchable hydraulic fracturing fluid.

Patients with repaired unilateral cleft lip with palate (UCLP) often show dysmorphology and distorted facial motion clinically, which can cause psychological issues. However, no report has clarified the details concerning distorted facial motion and the corresponding possible causative factors. In this study, we hypothesized that the physical properties of the scar and surrounding facial soft tissue might affect facial displacement while smiling in patients with UCLP (Cleft group). We thus examined the three-dimensional (3D) facial displacement while smiling in the Cleft and Control groups in order to determine whether or not the physical properties of facial soft tissues differ between the Cleft and Control groups and to examine the relationship between the physical properties of facial soft tissues on 3D facial displacement while smiling. Three-dimensional images at rest and while smiling as well as the facial physical properties (e.g. viscoelasticity) of both groups were recorded. Differences in terms of physical properties and facial displacement while smiling between the two groups were examined. To examine the relationship between facial surface displacement while smiling and physical properties, a canonical correlation analysis (CCA) was conducted. As a result, three typical abnormal features of smiling in the Cleft group compared with the Control group were noted: less upward and backward displacement on the scar area, downward movement of the lower lip, and a greater asymmetric displacement, including greater lateral displacement of the subalar on the cleft side while smiling and greater alar backward displacement on the non-cleft side. The Cleft group also showed greater elastic modulus at the upper lip on the cleft side, suggesting hardened soft tissue at the scar. The CCA showed that this hard scar significantly affected facial displacement, inducing less upward and backward displacement on the scar area and downward movement of the lower lip in patients with UCLP (correlation coefficient = 0.82, p = 0.04); however, there was no significant relationship between greater nasal alar lateral movement and physical properties of the skin at the scar. Based on these results, personalizing treatment options for dysfunction in facial expression generation may require quantification of the 3D facial morphology and physical properties of facial soft tissues.

International audience; Solid tumour growth is often associated with the accumulation of mechanical stresses acting on the surrounding host tissue. Due to tissue nonlinearity, the shear modulus of the peri-tumoural region inherits a signature from the tumour expansion which depends on multiple factors, including the soft tissue constitutive behaviour and its stress/strain state. Shear waves used in MR-elastography (MRE) sense the apparent change in shear modulus along their propagation direction, thereby probing the anisotropic stiffness field around the tumour. We developed an analytical framework for a heterogeneous shear modulus distribution using a thick-shelled sphere approximation of the tumour and soft tissue ensemble. A hyperelastic material (plastisol) was identified to validate the proposed theory in a phantom setting. A balloon-catheter connected to a pressure sensor was used to replicate the stress generated from tumour pressure and growth while MRE data were acquired. The shear modulus anisotropy retrieved from the reconstructed elastography data confirmed the analytically predicted patterns at various levels of inflation. An alternative measure, combining the generated deformation and the local wave direction and independent of the reconstruction strategy, was also proposed to correlate the analytical findings with the stretch probed by the waves. Overall, this work demonstrates that MRE in combination with non-linear mechanics, is able to identify the apparent shear modulus variation arising from the strain generated by a growth within tissue, such as an idealised model of tumour. Investigation in real tissue represents the next step to further investigate the implications of endogenous forces in tissue characterisation through MRE

We evaluated the long-term stability of a newly developed viscoelastic phantom made of polyacrylamide (PAAm) gel for magnetic resonance elastography (MRE) and ultrasound-based shear-wave elastography (US SWE). The stiffness of the cylindrical phantom was measured at 0, 13 and 18 months. Storage and loss moduli were measured with MRE, and shear-wave speed (SWS) was measured with US SWE. Long-term stability was evaluated in accordance with the Quantitative Imaging Biomarker Alliance (QIBA) profiles for each modality. The initial storage and loss moduli of the phantom were 5.01±0.22 and 1.11±0.15 respectively, and SWS was 2.57±0.04 m/s. The weight of the phantom decreased by 0.6% over the 18 months. When measured with MRE, the stiffness of the phantom decreased and changes to the storage and loss moduli were -3.0% and -4.6% between 0 and 13 months, and -4.3% and 0.0% between 0 and 18 months. The US measurements found that SWS decreased by 2.4% over the first 13 months and 3.6% at 18 months. These changes were smaller than the tolerances specified in the QIBA profiles, so the viscoelastic PAAm gel phantom fulfilled the condition for long-term stability. This new phantom has the potential to be used as a quality assurance and quality control phantom for MRE and US SWE.

Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary load bearing structure during physiological wrist motion, its geometry, mechanical properties, and the surgical placement of the scaffold are critical for performance optimisation. This study presents a patient-specific computational biomechanical evaluation of the effect of scaffold length, and positioning of the bone attachment sites. Through segmentation and image processing of medical image data for natural wrist motion, detailed 3D geometries as well as patient-specific physiological wrist motion could be derived. This data formed the input for detailed finite element analysis, enabling computational of scaffold stress and strain distributions, which are key predictors of scaffold structural integrity. The computational analysis demonstrated that longer scaffolds present reduced peak scaffold stresses and a more homogeneous stress state compared to shorter scaffolds. Furthermore, it was found that scaffolds attached at proximal sites experience lower stresses than those attached at distal sites. However, scaffold length, rather than bone terminal location, most strongly influences peak stress. For each scaffold terminal placement configuration, a basic metric was computed indicative of bone fracture risk. This metric was the minimum distance from the bone surface to the internal scaffold bone terminal. Analysis of this minimum bone thickness data confirmed further optimisation of terminal locations is warranted.

Background and purposePressure injuries remain a significant health care issue in various settings. The purpose of this study was to examine the relationship between a pressure redistributing foam mattress (PRFM) and the development of pressure injuries.MethodsThis study employed an observational prospective cohort study design. We enrolled 254 participants from the intensive care unit who were at risk of developing pressure injuries. Participants were exposed to either a nonpressure redistributing foam mattress (NPRFM), which was the standard mattress used at the study site, or a PRFM made of viscoelastic, temperature-sensitive, polyurethane memory foam. The patients’ assignment to either a PRFM or NPRFM was performed upon their admission, before the study eligibility screening. The relationship between the PRFM and the development of pressure injuries was studied using a logistic regression model.ResultsThe overall incidence of pressure injuries was 5.9% (15/254) in our study, with 1.6% (2/127) for participants who used a PRFM and 10.2% (13/127) for those using a NPRFM. After adjusting for potential confounding variables, use of a PRFM was associated with an 88% reduced risk of pressure injury development (OR = 0.12, 95% CI: 0.03, 0.56, P = 0.007). The use of a PRFM also contributed to a postponed occurrence of pressure injuries by 4.2 days on average in comparison with that of a NPRFM (P= 0.041).ConclusionsA PRFM is associated with a significantly reduced incidence and postponed occurrence of pressure injuries. It is recommended to use a PRFM for patients at risk of developing pressure injuries.

The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.

Despite the significant progress in characterizing mechanical functions of individual scleral extracellular matrix (ECM) components, the biomechanical contribution of sulfated glycosaminoglycans (sGAGs) is still poorly understood. The primary purpose of this study was to determine the possible function of sGAGs in scleral mechanical response by characterizing the tensile behavior of normal and sGAG-depleted samples. We used chondroitinase ABC solution to remove sGAGs from scleral samples that were dissected from posterior porcine eyes. We performed biochemical analyses for assessing the efficacy of sGAG removal protocol. Furthermore, we conducted stress-controlled uniaxial tensile tests to characterize the influence of sGAG removal on mechanical properties of sclera. The tensile behavior of scleral strips right after dissection and after being soaked in buffer was also determined. Biochemical analyses confirmed that 18 hour incubation in 0.125 U/ml Chondroitinase ABC solution removed over 90% of chondroitin and dermatan sGAGs. No significant difference was observed in the thickness/hydration of samples because of enzyme- and buffer-treated samples. Furthermore, it was found that sGAG depletion did not significantly alter the tangent modulus, energy dissipation, and peak strain of posterior scleral strips. It was concluded that sGAGs did not influence the stress-controlled viscoelastic tensile response of sclera.

Recent studies showed that wave intensity analysis (WIA) provides clinically valuable information about local and global cardiovascular function. Wave intensity (WI) is computed as the product of the pressure change and the velocity change during short time intervals. The major limitation of WIA in clinical practice is the need for invasive pressure measurement. Since vessel wall displacement can be measured non-invasively, the usage of WI will be expanded if the vessel wall dilation is used instead of pressure in derivation of WI waveform. Our goal in this study is to investigate the agreement between wall displacement-based WI and the pressure-based WI for different vessel wall models including linear elastic, nonlinear and viscoelastic cases. The arbitrary Eulerian Lagrangian finite element method is employed to solve the coupled fluid-structure interaction (FSI). Our computational models also include two types of vascular disease-related cases with geometrical irregularities, aneurysm and stenosis. Our results show that for vessels with linear elastic wall, the displacement-based WI is almost identical to the pressure-based WI. The existence of vessel irregularities does not impact the accuracy of displacement-based WI. However, in a viscoelastic wall where there is a phase difference between pressure and vessel wall dilation, displacement-based WI deviated from pressure-based WI. The error associated with this phase difference increased nonlinearly with increasing viscosity. This results in a maximum error of 6.8% and 7.13% for a regular viscoelastic vessel wall and an irregular viscoelastic vessel wall, respectively. A separate analysis has also been performed on the agreement of backward and forward running waves extracted from a decomposition of the displacement-based and pressure-based WI. Our findings suggest that displacement-based WI is a reliable method of WIA for large central arteries that do not show viscoelastic behaviors. This can be clinically significant since the required information can be measured non-invasively.

Hyaluronic acid injections have been a mainstay of arthritis treatment for decades. However, much controversy remains about their clinical efficacy and their potential mechanism of action. This approach to arthritis therapy is often called viscosupplementation, a term which is rooted in the elevated viscosity of the injected solutions. This terminology also suggests a mechanical pathway of action and further implies that their efficacy is dependent on viscosity. Notably, previous studies of the relationship between viscous properties of hyaluronic acid solutions and their clinical efficacy have not been definitive. Recently we developed an experimental and analytical framework for studying cartilage lubrication that captures the Stribeck-like behavior of cartilage in an elastoviscous transition curve. Here we apply this framework to study the lubricating behavior of six hyaluronan products currently used for injectable arthritis therapy in the US. Despite the fact that the source and chemical modifications endow these products with a range of lubricating properties, we show that the lubricating effect of all of these materials can be described by this Stribeck-like elastoviscous transition. Fitting this data to the elastoviscous transition model enables the calculation of effective lubricating viscosities for each material, which differ substantially from the viscosities measured using standard rheometry. Further we show that while data from standard rheometry are poor predictors of clinical performance of these materials, measurements of friction coefficient and effective lubricating viscosity correlate well (R2 = 0.77; p < 0.005) with assessments of improved clinical function reported previously. This approach offers both a novel method that can be used to evaluate potential clinical efficacy of hyaluronic acid formulations and provide new insight on their mode of action.

The protein composition, molecular weight distribution, and rheological properties of honey locust, mesquite, Kentucky coffee tree, and carob seed germs were compared against wheat gluten. Polymeric and Osborne fractionation protocols were used to assess biochemical properties. Dynamic oscillatory shear tests were performed to evaluate protein functionality. All samples had similar ratios of protein fractions as well as high molecular weight disulfide linked proteins except for the Kentucky coffee tree germ proteins, which were found to have lower molecular weight proteins with little disulfide polymerization. Samples were rich in acidic and polar amino acids (glutamic acid and arginine,). Rheological analyses showed that vital wheat gluten had the most stable network, while Kentucky coffee seed proteins had the weakest. High molecular weight disulfide linked glutenous proteins are a common, but not universal feature of pod bearing leguminous trees.

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat severe cases of acute respiratory or cardiac failure. Hemorrhagic complications represent one of the most common complications during ECMO, and can be life threatening. The purpose of this study was to elucidate pathophysiological mechanisms of ECMO-associated hemorrhagic complications and their impact on standard and viscoelastic coagulation tests. The study cohort included 27 patients treated with VV-ECMO or VA-ECMO. Hemostasis was evaluated using standard coagulation tests and viscoelastic parameters investigated with rotational thromboelastometry. Anticoagulation and hemorrhagic complications were analyzed for up to seven days depending on ECMO duration. Hemorrhagic complications developed in 16 (59%) patients. There were 102 discrete hemorrhagic episodes among 116 24-hour-intervals, of which 27% were considered to be clinically significant. The highest number of ECMO-associated hemorrhages occurred on the 2nd and 3rd day of treatment. Respiratory tract bleeding was the most common hemorrhagic complication, occurring in 62% of the 24-hour intervals. All 24-hours-intervals were divided into two groups: "with bleeding" and "without bleeding". The probability of hemorrhage was significantly associated with abnormalities of four parameters: increased international normalized ratio (INR, sensitivity 71%, specificity 94%), increased prothrombin time (PT, sensitivity 90%, specificity 72%), decreased intrinsic pathway maximal clot firmness (MCFin, sensitivity 76%, specificity 89%), and increased extrinsic pathway clot formation time (CFTex, sensitivity 77%, specificity 87%). In conclusions, early ECMO-associated hemorrhagic complications are related to one traditional and two novel viscoelastic coagulation abnormalities: PT/INR elevation, reduced maximum clot firmness due to intrinsic pathway dysfunction (MCFin), and prolonged clot formation time due to extrinsic pathway dysfunction (CFTex). When managing hemostasis during ECMO, derangements in PT/INR, MCFin and CFTex should be focused on.

Mechanical interactions between flowing and coagulated blood (thrombus) are crucial in dictating the deformation and remodeling of a thrombus after its formation in hemostasis. We propose a fully-Eulerian, three-dimensional, phase-field model of thrombus that is calibrated with existing in vitro experimental data. This phase-field model considers spatial variations in permeability and material properties within a single unified mathematical framework derived from an energy perspective, thereby allowing us to study effects of thrombus microstructure and properties on its deformation and possible release of emboli under different hemodynamic conditions. Moreover, we combine this proposed thrombus model with a particle-based model which simulates the initiation of the thrombus. The volume fraction of a thrombus obtained from the particle simulation is mapped to an input variable in the proposed phase-field thrombus model. The present work is thus the first computational study to integrate the initiation of a thrombus through platelet aggregation with its subsequent viscoelastic responses to various shear flows. This framework can be informed by clinical data and potentially be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions., Author summary Thromboembolism is associated with detachment of small thrombus pieces from the bulk in the blood vessel. These detached pieces, also known as emboli, travel through the blood flow and may block other vessels downstream, e.g., they may plug the deep veins of the leg, groin or arm, leading to venous thromboembolism (VTE). VTE is a significant cause of morbidity and mortality and it affects more than 900,000 people in the United States and result in approximately 100,000 deaths every year. Mechanical interaction between flowing blood and a thrombus is crucial in determining the deformation of the thrombus and the possibility of releasing emboli. In this study, we develop a phase-field model that is capable of describing the structural properties of a thrombus and its biomechanical properties under different blood flow conditions. Moreover, we combine this thrombus model with a particle-based model which simulates the initiation of the thrombus. This combined framework is the first computational study to simulate the development of a thrombus from platelet aggregation to its subsequent viscoelastic responses to various shear flows. Informed by clinical data, this framework can be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.

Dairy products exhibit several physical properties that are crucial to define whether we like the food or not: firmness, creaminess, thickness, or lightness. Viscosity changes the flow properties of food and influences the appearance and the consistency of a product; this control variable is important in most production stages-manufacture, processing, and storage. Viscosity of heterogeneous products at a given temperature depends on its composition and physical state of its substances. Although rheology provides a method to access the product viscosity, it lacks non-contact full-field monitoring. We apply a simple correlation analysis of laser speckle images to evaluate viscosity properties of dairy products. Our approach ensures robust measurements with high degree of detectability.

Knowledge of the biomechanical properties of the human cornea is crucial for understanding the development of corneal diseases and impact of surgical treatments (e.g., corneal laser surgery, corneal cross-linking). Using a Surface Force Apparatus we investigated the transient viscous response of the anterior cornea from donor human eyes compressed between macroscopic crossed cylinders. Corneal biomechanics was analyzed using linear viscoelastic theory and interpreted in the framework of a biphasic model of soft hydrated porous tissues, including a significant contribution from the pressurization and viscous flow of fluid within the corneal tissue. Time-resolved measurements of tissue deformation and careful determination of the relaxation time provided an elastic modulus in the range between 0.17 and 1.43 MPa, and fluid permeability of the order of 10(-13) m(4)/(N.s). The permeability decreased as the deformation was increased above a strain level of about 10%, indicating that the interstitial space between fibrils of the corneal stromal matrix was reduced under the effect of strong compression. This effect may play a major role in determining the observed rate-dependent non-linear stress-strain response of the anterior cornea, which underlies the shape and optical properties of the tissue.

Shear wave elastography is emerging as a clinically valuable diagnostic tool to differentiate between benign and malignant breast masses. Elastography techniques assume that soft tissue can be modelled as a purely elastic medium. However, this assumption is often violated as soft tissue exhibits viscoelastic properties. In order to explore the role of viscoelastic parameters in suspicious breast masses, a study was conducted on a group of patients using shear wave dispersion ultrasound vibrometry in the frequency range of 50-400 Hz. A total of 43 female patients with suspicious breast masses were recruited before their scheduled biopsy. Of those, 15 patients did not meet the data selection criteria. Voigt model based shear elasticity showed a significantly (p = 7.88x10(-6)) higher median value for the 13 malignant masses (16.76±13.10 kPa) compared to 15 benign masses (1.40±1.12 kPa). Voigt model based shear viscosity was significantly different (p = 4.13x10(-5)) between malignant (8.22±3.36 Pa-s) and benign masses (2.83±1.47 Pa-s). Moreover, the estimated time constant from the Voigt model, which is dependent on both shear elasticity and viscosity, differed significantly (p = 6.13x10(-5)) between malignant (0.68±0.33 ms) and benign masses (3.05±1.95 ms). Results suggest that besides elasticity, viscosity based parameters like shear viscosity and time constant can also be used to differentiate between malignant and benign breast masses.

The addition of a cosmetic glove to an upper limb prosthesis has a distinct effect on the cosmetic value, but its viscoelastic behaviour adds a substantial amount of stiffness and hysteresis to the system. As a result, the overall usability of the prosthesis is degraded. A novel negative stiffness element is designed to compensate for the cosmetic glove’s stiffness. A combination of linear helical springs and the concept of rolling link mechanisms has resulted in a Rolling Stiffness Compensation Mechanism (RSCM). Results show that the RSCM is capable of exerting a progressive negative stiffness characteristic and can be built small enough to fit inside a 33 mm diameter wrist. Using the RSCM, an otherwise voluntary opening toddler-sized prosthesis is converted into a voluntary closing device, reducing maximum operation forces down to 40 N with a combined efficiency of 52%. Further adjustments to the design are possible to further improve the efficiency of the mechanism. Moreover, changes in geometric relations of the mechanism offers possibilities for a wide range of prostheses and other applications.

A multi-mode nonlinear constitutive model for mucus is constructed directly from micro- and macro-rheology experimental data on cell culture mucus, and a numerical algorithm is developed for the culture geometry and idealized cilia driving conditions. This study investigates the roles that mucus rheology, wall effects, and HBE culture geometry play in the development of flow profiles and the shape of the air-mucus interface. Simulations show that viscoelasticity captures normal stress generation in shear leading to a peak in the air-mucus interface at the middle of the culture and a depression at the walls. Linear and nonlinear viscoelastic regimes can be observed in cultures by varying the hurricane radius and mean rotational velocity. The advection-diffusion of a drug concentration dropped at the surface of the mucus flow is simulated as a function of Peclet number., Author Summary In the lungs, the airway surface liquid protects the airway epithelium from inhaled pathogens and particulates. It is well known that failure to properly clear mucus from the airways leads to chronic, even fatal, lung infections. To date, there is no validated constitutive model capable of recapitulating mucus rheology under diverse, physiological stress and deformation conditions. This gap has hindered studies into the causal relationship between mucus rheology and mucociliary clearance. Our modeling-experimental approach fulfills several purposes: to implement linear and nonlinear constitutive modeling of mucus from micro- and macro-rheology, to test constitutive modeling in an independent experimental system, to build a coarse-grained model of the PCL-mucus boundary condition, to measure and understand modifications in mucociliary transport during and after deposition of a controlled drug concentration, to measure and simulate both the flow and stress fields throughout the mucus layer, and to measure and simulate how the advection profiles in the culture couple with diffusion of particulates landing on the air-mucus interface. These results lay the groundwork for extension of the code to three dimensions and more realistic metachronal wave boundary conditions, both in cell cultures and in airways.

Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests.

Biomechanical properties are an excellent health marker of biological tissues, however they are challenging to be measured in-vivo. Non-invasive approaches to assess tissue biomechanics have been suggested, but there is a clear need for more accurate techniques for diagnosis, surgical guidance and treatment evaluation. Recently air-puff systems have been developed to study the dynamic tissue response, nevertheless the experimental geometrical observations lack from an analysis that addresses specifically the inherent dynamic properties. In this study a viscoelastic finite element model was built that predicts the experimental corneal deformation response to an air-puff for different conditions. A sensitivity analysis reveals significant contributions to corneal deformation of intraocular pressure and corneal thickness, besides corneal biomechanical properties. The results show the capability of dynamic imaging to reveal inherent biomechanical properties in vivo. Estimates of corneal biomechanical parameters will contribute to the basic understanding of corneal structure, shape and integrity and increase the predictability of corneal surgery. © 2014 Kling et al., Spanish Government FIS2011-25637, European Research Council ERC-2011 AdG-294099 to SM. FPI-BES-2009-024560 Pre-doctoral Fellowship to SK.

Formation of bacterial colonies as biofilm on the surface/interface of various objects has the potential to impact not only human health and disease but also energy and environmental considerations. Biofilms can be regarded as soft materials, and comprehension of their shear response to external forces is a key element to the fundamental understanding. A mesoscale model has been presented in this article based on digitization of a biofilm microstructure. Its response under externally applied shear load is analyzed. Strain stiffening type behavior is readily observed under high strain loads due to the unfolding of chains within soft polymeric substrate. Sustained shear loading of the biofilm network results in strain localization along the diagonal direction. Rupture of the soft polymeric matrix can potentially reduce the intercellular interaction between the bacterial cells. Evolution of stiffness within the biofilm network under shear reveals two regimes: a) initial increase in stiffness due to strain stiffening of polymer matrix, and b) eventual reduction in stiffness because of tear in polymeric substrate.