Local Tissue Deformation Research Articles

Effects of elastic therapeutic taping on along-muscle fascicle local length changes: Magnetic resonance and diffusion tensor imaging based assessment

Elastic therapeutic taping is utilized for prevention and treatment of various neuromusculoskeletal disorders and sports injuries. Kinesio taping (KT) is a popular version of this practice. Despite being widely used to improve muscular function, an understanding of KT effects on muscular mechanics are lacking. Considering the continuity of the fascial system and its mechanical interaction with muscle fascicles intramuscularly, the aim was to test the following hypothesis: mechanical loading induced on the skin by KT leads to along-muscle fascicle local length changes and shear strains in the targeted muscle. Magnetic resonance imaging (MRI)-based local tissue deformation analyses and diffusion tensor imaging (DTI)-based fiber tracking analyzes were combined. Anatomical MRI and DTI were acquired for 5 healthy female volunteers in 3 conditions: (1) without tape, (2) following sham application, and (3) after KT application. Local length changes and shear strains were calculated using image registration between conditions (1–2) and (2–3). Non-parametric Wilcoxon signed-rank test was performed to compare the two conditions. Data pooled from all subjects show that KT-imposed along-muscle fascicle lengthening (mean ± SD 0.026 ± 0.020), shortening (0.032 ± 0.027) and shearing (0.087 ± 0.049) occur and are significantly higher than those caused by sham application (0.012 ± 0.010; 0.013 ± 0.015; 0.029 ± 0.021, respectively) (p < 0.001). KT induced along-muscle fascicle length changes locally show heterogeneity. Our findings indicate that KT affects both along-muscle fascicle length changes and shear strains. This can be explained by KT imposed myofascial loads over the skin being transmitted via the fascial system, non-uniformly manipulating the mechanical equilibrium locally at different parts along the muscle fascicles.

Scanning Laser Ophthalmoscopy Demonstrates Disc and Peripapillary Strain During Horizontal Eye Rotation in Adults

We used automated image analysis of scanning laser ophthalmoscopy (SLO) to investigate mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in adults. Deep learning analysis of optical images. The peripapillary region was imaged by SLO in central gaze, and 35° abduction and adduction, in younger and older healthy adults. Automated image registration was followed by deep learning-based optical flow analysis to track determine local tissue deformations quantified as horizontal, vertical, and shear strain maps relative to central gaze. Choroidal vessel displacements were observed when fundus pigment was light. Strains in the retina and disc could be quantified in 22 younger (mean ± SEM, 26 ± 5 years) and 19 older (64 ± 10 years) healthy volunteers. Strains were predominantly horizontal and greater for adduction than for abduction. During adduction, maximum horizontal strain was tensile in the nasal hemi-disc, and declined progressively with distance from it. Strain in the temporal hemi-retina during adduction was minimal, except for compressive strain on the disc of older subjects. In abduction, horizontal strains were less and largely confined to the disc, greater in older subjects, and generally tensile. Vertical and shear strains were small. Nasal to the disc, choroidal vessels shifted nasally relative to overlying peripapillary retinal vessels. Strain analysis during horizontal duction suggests that the optic nerve displaces the optic canal, choroid, and peripapillary sclera relative to the overlying disc and retina. This peripapillary shearing of the optic nerve relative to the choroid and sclera may be a driver of disc tilting and peripapillary atrophy.

Sim-to-Real Surgical Robot Learning and Autonomous Planning for Internal Tissue Points Manipulation Using Reinforcement Learning

Indirect simultaneous positioning (ISP), where internal tissue points are placed at desired locations indirectly through the manipulation of boundary points, is a type of subtask frequently performed in robotic surgeries. Although challenging due to complex tissue dynamics, automating the task can potentially reduce the workload of surgeons. This paper presents a sim-to-real framework for learning to automate the task without interacting with a real environment, and for planning preoperatively to find the grasping points that minimize local tissue deformation. A control policy is learned using deep reinforcement learning (DRL) in the FEM-based simulation environment and transferred to real-world situation. Grasping points are planned in the simulator by utilizing the trained policy using Bayesian optimization (BO). Inconsistent simulation performance is overcome by formulating the problem as a state augmented Markov decision process (MDP). Experimental results show that the learned policy places the internal tissue points accurately, and that the planned grasping points yield small tissue deformation among the trials. The proposed learning and planning scheme is able to automate internal tissue point manipulation in surgeries and has the potential to be generalized to complex surgical scenarios.

Quantifying how altered lacunar morphology and perilacunar tissue properties influence local mechanical environment of osteocyte lacunae using finite element modeling

Previous studies have demonstrated that osteocyte lacunar morphology and perilacunar bone tissue properties undergo alterations due to physiological and pathological processes such as aging, lactation, diseases, and treatments. However, the influence of these alterations on the apparent mechanical properties of the bone and the local mechanical environment of osteocyte lacunae has not been evaluated in detail. The goal of this study is to quantify the influence of osteocyte lacunar morphology and perilacunar tissue properties on local mechanical environment around lacunae and the apparent mechanical properties of the bone using three-dimensional FE models of lacunae networks with varying lacunar morphology and perilacunar properties based on previously reported experimental data. To attain this goal, a parametric study using models with different lacunar/perilacunar properties, including lacunar density (Lc.D), orientation (Lc.Φ), volume (Lc.V), and equancy (Lc.Eq), as well as perilacunar modulus (Pl.E), and size (Pl.S) was carried out. In addition, a specific case study using models derived from aged and young bone specimens was performed. Our results showed that the highly strained tissue around lacunae increased linearly with increasing Lc.D and Lc.V, reduced exponentially with decreasing angle of major axis of lacunae from the loading direction and with increasing Pl.E, and increased exponentially with increasing Pl.S. The change in apparent elastic modulus with modifications in lacunar morphology was very small whereas the change in perilacunar modulus had a more substantial influence on the apparent elastic modulus. Lacunar strain amplification was reduced by increasing Lc.Φ, and Pl.E and increased with increasing Lc.V within the range of 1.5 and 2.3. No significant difference was seen in the apparent elastic modulus of models derived from young and aged bone models. However, young bone showed substantially larger amount of highly strained tissue around lacunae compared to the aged bone. This difference was amplified when the perilacunar tissue property modifications were incorporated in the models. In summary, the results indicate that modifications in the osteocyte lacunar morphology and perilacunar tissue properties can significantly alter local tissue deformation around lacunae which may impact osteocyte mechanosensitivity.

Supracellular measurement of spatially varying mechanical heterogeneities in live monolayers

The mechanical properties of tissues have profound impacts on a wide range of biological processes such as embryo development (1,2), wound healing (3–6), and disease progression (7). Specifically, the spatially varying moduli of cells largely influence the local tissue deformation and intercellular interaction. Despite the importance of characterizing such a heterogeneous mechanical property, it has remained difficult to measure the supracellular modulus field in live cell layers with a high-throughput and minimal perturbation. In this work, we developed a monolayer effective modulus measurement by integrating a custom cell stretcher, light microscopy, and AI-based inference. Our approach first quantifies the heterogeneous deformation of a slightly stretched cell layer and converts the measured strain fields into an effective modulus field using an AI inference. This method allowed us to directly visualize the effective modulus distribution of thousands of cells virtually instantly. We characterized the mean value, SD, and correlation length of the effective cell modulus for epithelial cells and fibroblasts, which are in agreement with previous results. We also observed a mild correlation between cell area and stiffness in jammed epithelia, suggesting the influence of cell modulus on packing. Overall, our reported experimental platform provides a valuable alternative cell mechanics measurement tool that can be integrated with microscopy-based characterizations.

Normative healthy reference values for global and segmental 3D principal and geometry dependent strain from cine cardiac magnetic resonance imaging.

3-Dimensional (3D) myocardial deformation analysis (3D-MDA) enables novel descriptions of geometry-independent principal strain (PS). Applied to routine 2D cine cardiovascular magnetic resonance (CMR), this provides unique measures of myocardial biomechanics for disease diagnosis and prognostication. However, healthy reference values remain undefined. This study describes age- and sex-stratified reference values from CMR-based 3D-MDA, including 3D PS. One hundred healthy volunteers were prospectively recruited following institutional ethics approval and underwent CMR imaging. 3D-MDA was performed using validated software. Age- and sex-stratified global and segmental strain measures were derived for conventional geometry-dependent [circumferential (CS), longitudinal (LS), and radial (RS)] and geometry-independent [minimum (minPS) and maximum principal (maxPS)] directions of deformation. Layer-specific contraction angle interactions were determined using local minPS vectors. The average age was 43 ± 15years and 55% were women. Strain measures were higher in women versus men. 3D PS-based assessment of maximum tissue shortening (minPS) and maximum tissue thickening (maxPS) were greater than corresponding geometry-dependent markers of LS and RS, consistent with improved representation of local tissue deformations. Global maxPS amplitude best discriminated both age and sex. Segmental analyses showed greater strain amplitudes in apical segments. Transmural PS contraction angles were higher in females and showed a heterogeneous distribution across segments. In this study we provided age and sex-based reference values for 3D strain from CMR imaging, demonstrating improved capacity for 3D PS to document maximal local tissue deformations and to discriminate age and sex phenotypes. Novel markers of layer-specific strain angles from 3D PS were also described.

Growth orientations, rather than heterogeneous growth rates, dominate jaw joint morphogenesis in the larval zebrafish.

In early limb embryogenesis, synovial joints acquire specific shapes which determine joint motion and function. The process by which the opposing cartilaginous joint surfaces are moulded into reciprocal and interlocking shapes, called joint morphogenesis, is one of the least understood aspects of joint formation and the cell‐level dynamics underlying it are yet to be unravelled. In this research, we quantified key cellular dynamics involved in growth and morphogenesis of the zebrafish jaw joint and synthesised them in a predictive computational simulation of joint development. Cells in larval zebrafish jaw joints labelled with cartilage markers were tracked over a 48‐h time window using confocal imaging. Changes in distance and angle between adjacent cell centroids resulting from cell rearrangement, volume expansion and extracellular matrix (ECM) deposition were measured and used to calculate the rate and direction of local tissue deformations. We observed spatially and temporally heterogeneous growth patterns with marked anisotropy over the developmental period assessed. There was notably elevated growth at the level of the retroarticular process of the Meckel's cartilage, a feature known to undergo pronounced shape changes during zebrafish development. Analysis of cell dynamics indicated a dominant role for cell volume expansion in growth, with minor influences from ECM volume increases and cell intercalation. Cell proliferation in the joint was minimal over the timeframe of interest. Synthesising the dynamic cell data into a finite element model of jaw joint development resulted in accurate shape predictions. Our biofidelic computational simulation demonstrated that zebrafish jaw joint growth can be reasonably approximated based on cell positional information over time, where cell positional information derives mainly from cell orientation and cell volume expansion. By modifying the input parameters of the simulation, we were able to assess the relative contributions of heterogeneous growth rates and of growth orientation. The use of uniform rather than heterogeneous growth rates only minorly impacted the shape predictions, whereas isotropic growth fields resulted in altered shape predictions. The simulation results suggest that growth anisotropy is the dominant influence on joint growth and morphogenesis. This study addresses the gap of the cellular processes underlying joint morphogenesis, with implications for understanding the aetiology of developmental joint disorders such as developmental dysplasia of the hip and arthrogryposis.

Transpupillary collagen photocrosslinking for targeted modulation of ocular biomechanics

The central vision-threatening event in glaucoma is dysfunction and loss of retinal ganglion cells (RGCs), thought to be promoted by local tissue deformations. Here, we sought to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, i.e. the scleral region immediately adjacent to the optic nerve head. Previous scleral stiffening studies to treat glaucoma or myopia have used either pan-scleral stiffening (not regionally selective) or regionally selective stiffening with limited access to the posterior globe. We present a method for selectively stiffening the peripapillary sclera using a transpupillary annular light beam to activate methylene blue administered by retrobulbar injection. Unlike prior approaches to photocrosslinking in the eye, this approach avoids the damaging effects of ultraviolet light by employing red light. This targeted photocrosslinking approach successfully stiffened the peripapillary sclera at 6 weeks post-treatment, as measured by whole globe inflation testing. Specifically, strain was reduced by 47% when comparing treated vs. untreated sclera within the same eye (n = 7, p=0.0064) and by 54% when comparing the peripapillary sclera of treated vs. untreated eyes (n = 7, p<0.0001). Post-treatment characterization of RGCs (optic nerve axon counts/density, and grading), retinal function (electroretinography), and retinal histology revealed that photocrosslinking was associated with some ocular toxicity. We conclude that a transpupillary photocrosslinking approach enables selective scleral stiffening targeted to the peripapillary region that may be useful in future treatments of glaucoma.

Multiscale integration of environmental stimuli in plant tropism produces complex behaviors

Plant tropism refers to the directed movement of an organ or organism in response to external stimuli. Typically, these stimuli induce hormone transport that triggers cell growth or deformation. In turn, these local cellular changes create mechanical forces on the plant tissue that are balanced by an overall deformation of the organ, hence changing its orientation with respect to the stimuli. This complex feedback mechanism takes place in a three-dimensional growing plant with varying stimuli depending on the environment. We model this multiscale process in filamentary organs for an arbitrary stimulus by explicitly linking hormone transport to local tissue deformation leading to the generation of mechanical forces and the deformation of the organ in three dimensions. We show, as examples, that the gravitropic, phototropic, nutational, and thigmotropic dynamic responses can be easily captured by this framework. Further, the integration of evolving stimuli and/or multiple contradictory stimuli can lead to complex behavior such as sun following, canopy escape, and plant twining.

Influence of Nanotopography on Early Bone Healing during Controlled Implant Loading

Nanoscale surface modifications influence peri-implant cell fate decisions and implant loading generates local tissue deformation, both of which will invariably impact bone healing. The objective of this study is to determine how loading affects healing around implants with nanotopography. Implants with a nanoporous surface were placed in over-sized osteotomies in rat tibiae and held stable by a system that permits controlled loading. Three regimens were applied: (a) no loading, (b) one daily loading session with a force of 1.5N, and (c) two such daily sessions. At 7 days post implantation, animals were sacrificed for histomorphometric and DNA microarray analyses. Implants subjected to no loading or only one daily loading session achieved high bone-implant contact (BIC), bone-implant distance (BID) and bone formation area near the implant (BFAt) values, while those subjected to two daily loading sessions showed less BFAt and BIC and more BID. Gene expression profiles differed between all groups mainly in unidentified genes, and no modulation of genes associated with inflammatory pathways was detected. These results indicate that implants with nanotopography can achieve a high level of bone formation even under micromotion and limit the inflammatory response to the implant surface.

Mosquito proboscis-inspired needle insertion to reduce tissue deformation and organ displacement

This study investigates mosquito proboscis-inspired (MPI) insertion applied to the clinically used biopsy needle to reduce tissue deformation and organ displacement. Advanced medical imagining has enabled early-stage identification of cancerous lesions that require needle biopsy for minimally invasive tissue sampling and pathological analysis. Accurate cancer diagnosis depends on the accuracy of needle deployment to the targeted cancerous lesion site. However, currently available needle delivery systems deform and move soft tissue and organs, leading to a non-diagnostic biopsy or undersampling of the target. Two features inspired by the mosquito proboscis were adopted for MPI insertion in prostate biopsy: (1) the harpoon-shape notches at the needle tip and (2) reciprocating needle-cannula motions for incremental insertion. The local tissue deformation and global prostate displacement during the MPI vs. traditional direct insertions were quantified by optically tracking the displacement of particle-embedded tissue-mimicking phantoms. Results show that the MPI needle insertion reduced both local tissue deformation and global prostate displacement because of the opposite needle-cannula motions and notches which stabilized and reduced the tissue deformation during insertion. Findings provide proof of concept for MPI insertion in the clinical biopsy procedures as well as insights of needle–tissue interaction for future biopsy technology development.

Metabolomics analysis of Lycium barbarum leaves after Aceria pallida infestation

Aceria pallida is one of the most common pests in the main production areas of Lycium barbarum in China. The mite mainly feeds on foliage, leading to local tissue deformation and formation of massive galls, which seriously affects the growth and yield of L. barbarum. However, little is known about the influence of galling organisms on plant primary and secondary metabolism. In order to compare the metabolites differences between healthy and the mite infested leaves of wolfberry, and provide a scientific basis for the development and utilization of the galled leaves, L. barbarum seedlings were infested with A. pallida artificially in the laboratory, the metabolites of L. barbarum leaves were determined by LC-MS/MS. Our results showed that the leaves were rich in amino acids and flavonoid compounds. A total of 204 compounds from 16 classes were detected in L. barbarum leaves based on LC-MS/MS. The primary metabolites are mainly amino acids, and the secondary metabolites are mainly organic acids and flavonoids. The content of the metabolite in the leaves of L. barbarum was significantly affected by the mite, 30 metabolites such as flavonoids and phenylpropanoids were significantly changed, 21 metabolites were up-regulated and 9 metabolites were down-regulated significantly. There were 8 compounds which has pharmacological and biological activity, such as eriodictyol, isorhamnetin-3-O-neohesperidoside and scopoletin up-regulated significantly. Based on the above findings, we suggest that the galled leaves of L.barbarum have a potential to be developed in the future.

Magnetic resonance imaging to estimate tissue deformations during penile clamp application: A case series

Background: Penile clamps provide a means of preventing urinary incontinence in males following radical prostatectomy. In order for the devices to function, significant mechanical loads need to be applied to the penile tissues to close the urethra. However, such loads have the potential to cause damage to the vulnerable skin and underlying soft tissues. Accordingly, the study aimed to estimate the magnitudes of tissue deformations resulting from penile clamp application in three individual cases. Methods: Three individuals were recruited who currently use penile clamps to manage urinary incontinence following radical prostatectomy. Magnetic resonance images (MRI) of the penis were taken to produce a series of high contrast coronal and sagittal images both before and during the application of two commercially available clamps, modified for MRI compatibility. Tissue thickness measurements were estimated with the clamps in-situ and normalised to the unloaded baseline state. Results: The estimated magnitude of tissue deformations resulting from clamp application ranged between 68% and 84%. There were minimal differences in these deformations between the clamp designs, both of which appeared effective in closing the urethra. Local stress concentrations were observed in the tissues, which were deformed around the shape of the clamp. Conclusions: MRI enabled quantification of local tissue deformation during penile clamp application. The results revealed that clamps created large tissue deformations in all three cases, regardless of design. This information could inform the development of new clamp designs and materials to minimise the potential for tissue damage. Level of evidence: 4

Automated Analysis of Microscale Cardiac Contractile Dynamics from Intravital Multiphoton Microscopy in Mouse Ventricle

BackgroundMultiphoton microscopy (MPM) has enabled in vivo time‐lapse imaging of the heart that shows motion of cells within the tissue with micrometer resolution. We developed automated analysis techniques to quantify cellular motion from in vivo cardiac MPM images throughout the cardiac cycle.MethodsIntravital cardiac MPM was performed on ventilated, male and female, 4–6 month‐old, C57Bl6 mice (n=9). MPM image volumes (100 μm deep) of the beating mouse left ventricle were acquired at 30 frames per second while recording the electrocardiogram and respiratory pressure (Fig. a). Image volumes were reconstructed by assembling lines acquired nearest to a specified point in the cardio‐respiratory phase space. Bulk‐tissue motion was calculated from the three‐dimensional translational transformation that best aligned images at each point of the cardiac cycle to a reference image at the most stable portion of the cardio‐respiratory phase space (respiratory 50%, cardiac 80%). After bulk‐tissue motion was subtracted, local tissue deformation was extracted via non‐rigid registration of the reconstructed images to the reference image and divergence was calculated from the resulting vector field. Analysis methods were applied to images before and after epinephrine injection (50 μg intramuscular), and following focal sterile injury by laser irradiation (FSI).ResultsVolumes were reconstructed in 50 intervals across the cardiac cycle that show vasculature (intravenous Texas‐red dextran, red) and cardiomyocytes and leukocytes (rhodamine 6G, cyan) moving across the field of view (Fig. b–c). Automated analysis of bulk‐tissue motion (Fig. d–e) indicated maximum displacements occurring at 16 % (anterior‐posterior direction), 36 % (superior‐inferior) and 38 % (epi‐endocardial) of the cardiac cycle. The calculated epi‐endocardial motion amplitude correlated with stroke volume (R2=0.35) measured by echocardiography in the same animal one day before MPM imaging. Automated analysis of local tissue deformation indicated a maximum absolute deformation occurring at 10 % of the cardiac cycle (Fig. f). Comparison to manual feature tracking across the cardiac cycle validated the automated measurements. Rigid and non‐rigid motion analysis techniques were applied to epinephrine stress test and focal sterile injury (FSI) lesion models showing, respectively, increased and decreased bulk‐tissue and local deformation and divergence.ConclusionsWe have shown and applied novel, fast, and accurate techniques for characterizing cardiac motion from in vivo cardiac MPM to study the performance of contractile cells in the heart during health and disease.Support or Funding InformationAmerican Heart Association (17POST33680127), National Institutes of Health (5R21EB024694‐03), and National Science Foundation (DBI‐1707312).Figure 1

A poro-hyper-viscoelastic rate-dependent constitutive modeling for the analysis of brain tissues

In this paper, the dynamic behavior of bovine brain tissue, measured from in-vitro unconfined compression tests, is examined and represented through a viscoelastic biphasic model. The experiments have been carried out under three compression speeds of 10, 100, and 1000 mm/s. The results exhibited significant rate-dependent behavior. The brain tissue is modeled as a biphasic continuum consisting of a compressible solid matrix, fully saturated with an incompressible interstitial fluid. The governing equations based on conservation of mass and momentum are used to describe the solid-fluid interactions. An inverse scheme is employed in which a finite element model runs iteratively to optimize constitutive constants. The obtained material parameters of the proposed biphasic model show relatively good agreement (R2 ≥ 0.96) with the experimental tissue mechanical responses at different rates. The model can successfully capture the key aspects of the rate-dependency for both solid and fluid phases under large strain deformation. This poro-hyper viscoelastic model can effectively estimate the global and local rate-dependent tissue deformations, the spatial variations in pore spaces, hydrostatic pressure as well as fluid diffusion through the tissue.

The Relationship Between Scleral Strain Change and Differential Cumulative Intraocular Pressure Exposure in the Nonhuman Primate Chronic Ocular Hypertension Model

PurposeTo determine the relationship between peripapillary scleral strain change and cumulative differential IOP exposure in nonhuman primates (NHPs) with unilateral chronic ocular hypertension.MethodsPosterior scleral shells from 6 bilaterally normal and 10 unilateral chronic ocular hypertension NHPs were pressurized from 5 to 45 mm Hg, and the resulting full-field, three-dimensional, scleral surface deformations were acquired using laser speckle interferometry. Scleral tensile strain (local tissue deformation) was calculated by analytical differentiation of the displacement field; zero strain was assumed at 5 mm Hg. Maximum principal strain was used to represent the scleral strain, and strains were averaged over a 15°-wide (∼3.6-mm) circumpapillary region adjacent to the ONH. The relative difference in mean strain was calculated between fellow eyes and compared with the differential cumulative IOP exposure within NHPs during the study period. The relationship between the relative difference in scleral strain and the differential cumulative IOP exposure in fellow eyes was assessed using an F test and quadratic regression model.ResultsRelative differential scleral tensile strain was significantly associated with differential cumulative IOP exposure in contralateral eyes in the chronic ocular hypertension NHPs, with the bilaterally normal NHPs showing no significant strain difference between fellow eyes. The sclera in the chronic ocular hypertension eyes was more compliant than in their fellow eyes at low levels of differential cumulative IOP exposure, but stiffer at larger differential IOPs (P < 0.0001).ConclusionsThese cross-sectional findings suggest that longitudinal IOP-induced changes in scleral mechanical behavior are dependent on the magnitude of differential cumulative IOP exposure.

The Effect of Articular Cartilage Focal Defect Size and Location in Whole Knee Biomechanics Models.

Articular cartilage focal defects are common soft tissue injuries potentially linked to osteoarthritis (OA) development. Although several defect characteristics likely contribute to osteoarthritis, their relationship to local tissue deformation remains unclear. Using finite element models with various femoral cartilage geometries, we explore how defects change cartilage deformation and joint kinematics assuming loading representative of the maximum joint compression during the stance phase of gait. We show how defects, in combination with location-dependent cartilage mechanics, alter deformation in affected and opposing cartilages, as well as joint kinematics. Small and average sized defects increased maximum compressive strains by approximately 50% and 100%, respectively, compared to healthy cartilage. Shifts in the spatial locations of maximum compressive strains of defect containing models were also observed, resulting in loading of cartilage regions with reduced initial stiffnesses supporting the new, elevated loading environments. Simulated osteoarthritis (modeled as a global reduction in mean cartilage stiffness) did not significantly alter joint kinematics, but exacerbated tissue deformation. Femoral defects were also found to affect healthy tibial cartilage deformations. Lateral femoral defects increased tibial cartilage maximum compressive strains by 25%, while small and average sized medial defects exhibited decreases of 6% and 15%, respectively, compared to healthy cartilage. Femoral defects also affected the spatial distributions of deformation across the articular surfaces. These deviations are especially meaningful in the context of cartilage with location-dependent mechanics, leading to increases in peak contact stresses supported by the cartilage of between 11% and 34% over healthy cartilage.

Fluid absorption by skin tissue during intradermal injections through hollow microneedles

Hollow microneedles are an emerging technology for delivering drugs and therapeutics, such as vaccines and insulin, into the skin. Although the benefits of intradermal drug delivery have been known for decades, our understanding of fluid absorption by skin tissue has been limited due to the difficulties in imaging a highly scattering biological material such as skin. Here, we report the first real-time imaging of skin tissue at the microscale during intradermal injections through hollow microneedles, using optical coherence tomography. We show that skin tissue behaves like a deformable porous medium and absorbs fluid by locally expanding rather than rupturing to form a single fluid filled cavity. We measure the strain distribution in a cross section of the tissue to quantify local tissue deformation, and find that the amount of volumetric expansion of the tissue corresponds closely to the volume of fluid injected. Mechanically restricting tissue expansion limits fluid absorption into the tissue. Our experimental findings can provide insights to optimize the delivery of drugs into skin for different therapeutic applications, and to better model fluid flow into biological tissue.

Mechanically Induced Ectopy via Stretch-Activated Cation-Nonselective Channels Is Caused by Local Tissue Deformation and Results in Ventricular Fibrillation if Triggered on the Repolarization Wave Edge (Commotio Cordis).

External chest impacts (commotio cordis) can cause mechanically induced premature ventricular excitation (PVEM) and, rarely, ventricular fibrillation (VF). Because block of stretch-sensitive ATP-inactivated potassium channels curtailed VF occurrence in a porcine model of commotio cordis, VF has been suggested to arise from abnormal repolarization caused by stretch activation of potassium channels. Alternatively, VF could result from abnormal excitation by PVEM, overlapping with normal repolarization-related electric heterogeneity. Here, we investigate mechanisms and determinants of PVEM induction and its potential role in commotio cordis-induced VF. Subcontusional mechanical stimuli were applied to isolated rabbit hearts during optical voltage mapping, combined with pharmacological block of ATP-inactivated potassium or stretch-activated cation-nonselective channels. We demonstrate that local mechanical stimulation reliably triggers PVEM at the contact site, with inducibility predicted by local tissue indentation. PVEM induction is diminished by pharmacological block of stretch-activated cation-nonselective channels. In hearts where electrocardiogram T waves involve a well-defined repolarization edge traversing the epicardium, PVEM can reliably provoke VF if, and only if, the mechanical stimulation site overlaps the repolarization wave edge. In contrast, application of short-lived intraventricular pressure surges neither triggers PVEM nor changes repolarization. ATP-inactivated potassium channel block has no effect on PVEM inducibility per se, but shifts it to later time points by delaying repolarization and prolonging refractoriness. Local mechanical tissue deformation determines PVEM induction via stretch-activation of cation-nonselective channels, with VF induction requiring PVEM overlap with the trailing edge of a normal repolarization wave. This defines a narrow, subject-specific vulnerable window for commotio cordis-induced VF that exists both in time and in space.

Fluid-structure interaction including volumetric coupling with homogenised subdomains for modeling respiratory mechanics.

In this article, a novel approach is presented for combining standard fluid-structure interaction with additional volumetric constraints to model fluid flow into and from homogenised solid domains. The proposed algorithm is particularly interesting for investigations in the field of respiratory mechanics as it enables the mutual coupling of airflow in the conducting part and local tissue deformation in the respiratory part of the lung by means of a volume constraint. In combination with a classical monolithic fluid-structure interaction approach, a comprehensive model of the human lung can be established that will be useful to gain new insights into respiratory mechanics in health and disease. To illustrate the validity and versatility of the novel approach, three numerical examples including a patient-specific lung model are presented. The proposed algorithm proves its capability of computing clinically relevant airflow distribution and tissue strain data at a level of detail that is not yet achievable, neither with current imaging techniques nor with existing computational models. Copyright © 2016 John Wiley & Sons, Ltd.