The anisotropic and region-dependent mechanical response of wrap-around tendons under tensile, compressive and combined multiaxial loads.

The present work reports on the multiaxial region and orientation-dependent mechanical properties of two porcine wrap-around tendons under tensile, compressive and combined loads based on an extensive study with n=175 samples. The results provide a detailed dataset of the anisotropic tensile and compressive longitudinal properties and document a pronounced tension-compression asymmetry. Motivated by the physiological loading conditions of these tendons, which include transversal compression at bony abutments in addition to longitudinal tension, we systematically investigated the change in axial tension when the tendon is compressed transversally along one or both perpendicular directions. The results reveal that the transversal compression can increase axial tension (proximal-distal direction) in both cases to orders of 30%, yet by a larger amount in the first case (transversal compression in anterior-posterior direction), which seems to be more relevant for wrap-around tendons in-vivo. These quantitative measurements are in line with earlier findings on auxetic properties of tendon tissue, but show for the first time the influence of this property on the stress response of the tendon, and may thus reveal an important functional principle within these essential elements of force transmission in the body. STATEMENT OF SIGNIFICANCE: The work reports for the first time on multiaxial region and orientation-dependent mechanical properties of wrap-around tendons under various loads. The results indicate that differences in the mechanical properties exist between zones that are predominantly in a uniaxial tensile state and those that experience complex load states. The observed counterintuitive increase of the axial tension upon lateral compression points at auxetic properties of the tendon tissue which may be pivotal for the function of the tendon as an element of the musculoskeletal system. It suggests that the tendon's performance in transmitting forces is not diminished but enhanced when the action line is deflected by a bony pulley around which the tendon wraps, representing an important functional principle of tendon tissue.

Regional differences in stomach stretch during organ filling and their implications on the mechanical stress response.

As part of the digestive system, the stomach plays a crucial role in the health and well-being of an organism. It produces acids and performs contractions that initiate the digestive process and begin the break-up of ingested food. Therefore, its mechanical properties are of interest. This study includes a detailed investigation of strains in the porcine stomach wall during passive organ filling. In addition, the observed strains were applied to tissue samples subjected to biaxial tensile tests. The results show inhomogeneous strains during filling, which tend to be higher in the circumferential direction (antrum: 13.2%, corpus: 22.0%, fundus: 67.8%), compared to the longitudinal direction (antrum: 4.8%, corpus: 24.7%, fundus: 50.0%) at a maximum filling of 3500 ml. Consequently, the fundus region experienced the greatest strain. In the biaxial tensile experiments, the corpus region appeared to be the stiffest, reaching nominal stress values above 400 kPa in the circumferential direction, whereas the other regions only reached stress levels of below 50 kPa in both directions for the investigated stretch range. Our findings gain new insight into stomach mechanics and provide valuable data for the development and validation of computational stomach models.

Influence of muscle length on the three-dimensional architecture and aponeurosis dimensions of rabbit calf muscles.

The function of a muscle is highly dependent on its architecture, which is characterized by the length, pennation, and curvature of the fascicles, and the geometry of the aponeuroses. During in vivo function, muscles regularly undergo changes in length, thereby altering their architecture. During passive muscle lengthening, fascicle length (FL) generally increases and the angle of fascicle pennation (FP) and the fascicle curvature (FC) decrease, while the aponeuroses increase in length but decrease in width. Muscles are differently structured, making their change during muscle lengthening complex and multifaceted. To obtain comprehensive data on architectural changes in muscles during passive length, the present study determined the three-dimensional fascicle geometry of rabbit M. gastrocnemius medialis (GM), M. gastrocnemius lateralis (GL), and M. plantaris (PLA). For this purpose, the left and right legs of three rabbits were histologically fixed at targeted ankle joint angles of 95° (short muscle length [SML]) and 60° (long muscle length [LML]), respectively, and the fascicles were tracked by manual three-dimensional digitization. In a second set of experiments, the GM aponeurosis dimensions of ten legs from five rabbits were determined at varying muscle lengths via optical marker tracking. The GM consisted of a uni-pennated compartment, whereas the GL and PLA contained multiple compartments of differently pennated fascicles. In the LML compared to the SML, the GM, GL, and PLA had on average a 41%, 29%, and 41% increased fascicle length, and a 30%, 25%, and 33% decrease in fascicle pennation and a 32%, 11%, and 35% decrease in fascicle curvature, respectively. Architectural properties were also differentiated among the different compartments of the PLA and GL, allowing for a more detailed description of their fascicle structure and changes. It was shown that the compartments change differently with muscle length. It was also shown that for each degree of ankle joint angle reduction, the proximal GM aponeurosis length increased by 0.11%, the aponeurosis width decreased by 0.22%, and the area was decreased by 0.20%. The data provided improve our understanding of muscles and can be used to develop and validate muscle models.

Process Parameters and Geometry Effects on Piezoresistivity in Additively Manufactured Polymer Sensors.

The current work experimentally determined how the initial resistance and gauge factor in additively manufactured piezoresistive sensors are affected by the material, design, and process parameters. This was achieved through the tensile testing of sensors manufactured with different infill angles, layer heights, and sensor thicknesses using two conductive polymer composites. Linear regression models were then used to analyze which of the input parameters had significant effects on the sensor properties and which interaction effects existed. The findings demonstrated that the initial resistance in both materials was strongly dependent on the sensor geometry, decreasing as the cross-sectional area was increased. The resistance was also significantly influenced by the layer height and the infill angle, with the best variants achieving a resistance that was, on average, 22.3% to 66.5% lower than less-favorable combinations, depending on the material. The gauge factor was most significantly affected by the infill angle and, depending on the material, by the layer height. Of particular interest was the finding that increasing in the infill angle resulted in an increase in the sensitivity that outweighed the associated increase in the initial resistance, thereby improving the gauge factor by 30.7% to 114.6%, depending on the material.

A geometry model of the porcine stomach featuring mucosa and muscle layer thicknesses.

The stomach is a vital organ responsible for food storage, digestion, and transport. Stomach diseases are of great economic and medical importance and require a large number of bariatric surgeries every year. To improve medical interventions, in silico modeling of the gastrointestinal tract has gained popularity in recent years to study stomach functioning. Because of the great structural and nutritional similarity between the porcine and human stomach, the porcine stomach is a suitable surrogate for the development and validation of gastric models. This study presents a realistic 3D geometry model of the porcine stomach based on a photogrammetric reconstruction of a real organ. Layer thicknesses of the stomach wall's mucosa and tunica muscularis were determined by more than 1900 manual measurements at different locations. Layer thickness distributions show mean mucosal and muscle thicknesses of 2.29 ± 0.45 mm and 2.83 ± 0.99 mm, respectively. In general, layer thicknesses increase from fundus (mucosa: 1.82 ± 0.19 mm, muscle layer: 2.59 ± 0.32 mm) to antrum (mucosa: 2.69 ± 0.31 mm, muscle layer: 3.73 ± 1.05 mm). The analysis of stomach asymmetry with respect to an idealized symmetrical stomach model, an approach often used in the literature, revealed volumetric deviations of 45%, 15%, and 92% for the antrum, corpus, and fundus, respectively. The present work also suggests an algorithm for the computation of longitudinal and circumferential directions at local points. These directions are useful for the implementation of material anisotropy. In addition, we present data on the passive pressure-volume relationship of the organ and perform an exemplary finite-element simulation, where we demonstrate the applicability of the model. We encourage others to utilize the geometry model featuring profound asymmetry for future model-based investigations on stomach functioning.

Three-dimensional multi-field modelling of gastric arrhythmias and their effects on antral contractions.

The contraction activation of smooth muscle in the stomach wall (SW) is coordinated by slow electrical waves. The interstitial cells of Cajal (ICC), specialised pacemaker cells, initiate and propagate these slow waves. By establishing an electrically coupled network, each ICC adjusts its intrinsic pacing frequency to a single dominant frequency, to be a key aspect in modelling the electrophysiology of gastric tissue. In terms of modelling, additional fields associated with electrical activation, such as voltage-dependent calcium influx and the resulting deformation, have hardly been considered so far. Here we present a three-dimensional model of the electro-chemomechanical activation of gastric smooth muscle contractions. To reduce computational costs, an adaptive multi-scale discretisation strategy for the temporal resolution of the electric field is used. The model incorporates a biophysically based model of gastric ICC pacemaker activity that aims to simulate stable entrainment and physiological conduction velocities of the electrical slow waves. Together with the simulation of concomitant gastric contractions and the inclusion of a mechanical feedback mechanism, the model is used to study dysrhythmias of gastric slow waves induced by abnormal stretching of the antral SW. The model is able to predict the formation of stretch-induced gastric arrhythmias, such as the emergence of an ectopic pacemaker in the gastric antrum. The results show that the ectopic event is accompanied by smooth muscle contraction and, although it disrupts the normal propagation pattern of gastric slow electrical waves, it can also catalyse the process of handling indigestible materials that might otherwise injure the gastric SW.

On a three-dimensional model for the description of the passive characteristics of skeletal muscle tissue.

In this work, a three-dimensional model was developed to describe the passive mechanical behaviour of anisotropic skeletal muscle tissue. To validate the model, orientation-dependent axial ([Formula: see text], [Formula: see text], [Formula: see text]) and semi-confined compression experiments (mode I, II, III) were performed on soleus muscle tissue from rabbits. In the latter experiments, specimen deformation is prescribed in the loading direction and prevented in an additional spatial direction, fibre compression at [Formula: see text] (mode I), fibre elongation at [Formula: see text] (mode II) and a neutral state of the fibres at [Formula: see text] where their length is kept constant (mode III). Overall, the model can adequately describe the mechanical behaviour with a relatively small number of model parameters. The stiffest tissue response during orientation-dependent axial compression ([Formula: see text] kPa) occurs when the fibres are oriented perpendicular to the loading direction ([Formula: see text]) and are thus stretched during loading. Semi-confined compression experiments yielded the stiffest tissue ([Formula: see text] kPa) in mode II when the muscle fibres are stretched. The extensive data set collected in this study allows to study the different error measures depending on the deformation state or the combination of deformation states.

Correlating the microstructural architecture and macrostructural behaviour of the brain.

The computational simulation of pathological conditions and surgical procedures, for example the removal of cancerous tissue, can contribute crucially to the future of medicine. Especially for brain surgery, these methods can be important, as the ultra-soft tissue controls vital functions of the body. However, the microstructural interactions and their effects on macroscopic material properties remain incompletely understood. Therefore, we investigated the mechanical behaviour of brain tissue under three different deformation modes, axial tension, compression, and semi-confined compression, in different anatomical regions, and for varying axon orientation. In addition, we characterised the underlying microstructure in terms of myelin, cells, glial cells and neuron area fraction, and density. The correlation of these quantities with the material parameters of the anisotropic Ogden model reveals a decrease in shear modulus with increasing myelin area fraction. Strikingly, the tensile shear modulus correlates positively with cell and neuronal area fraction (Spearman's correlation coefficient of rs=0.40 and rs=0.33), whereas the compressive shear modulus decreases with increasing glial cell area (rs=-0.33). Our study finds that tissue non-linearity significantly depends on the myelin area fraction (rs=0.47), cell density (rs=0.41) and glial cell area (rs=0.49). Our results provide an important step towards understanding the micromechanical load transfer that leads to the non-linear macromechanical behaviour of the brain. STATEMENT OF SIGNIFICANCE: Within this article, we investigate the mechanical behaviour of brain tissue under three different deformation modes, in different anatomical regions, and for varying axon orientation. Further, we characterise the underlying microstructure in terms of various constituents. The correlation of these quantities with the material parameters of the anisotropic Ogden model reveals a decrease in shear modulus with increasing myelin area fraction. Strikingly, the tensile shear modulus correlates positively with cell and neuronal area fraction, whereas the compressive shear modulus decreases with increasing glial cell area. Our study finds that tissue non-linearity significantly depends on the myelin area fraction, cell density, and glial cell area. Our results provide an important step towards understanding the micromechanical load transfer that leads to the non-linear macromechanical behaviour of the brain.

A pilot study on active and passive ex vivo characterisation of the urinary bladder and its impact on three-dimensional modelling.

Insight into the global deformation of the urinary bladder during passive and active phases is crucial for understanding the biomechanics and function of the organ. Therefore, in the present study, the three-dimensional deformations of the porcine urinary bladder were investigated using 10 cameras in ex vivo experiments. Voltages between 20 V and 40 V were applied to induce contraction without outflow (isovolumetric) and against different back pressures (isobaric). The fluid volume in the bladder and the fluid volume pushed out of the bladder in the active state were measured. During filling, a roughly constant pressure of 2.5-4 cmH2O was measured for a large volume range, followed by a steep increase. Overall, the urinary bladder shape changes from elliptical to spherical in the active phase, resulting in a more homogeneous stress field. The active pressure decreases with increasing volume, while the actively generated stress increases up to 65 kPa at the maximum volume examined. Smaller filling volumes and lower back pressures allowed complete emptying, whereas higher back pressures prevent full emptying from larger filling states. Finally, a recently developed three-dimensional model was used to describe the active and passive bladder characteristics in order to qualitatively represent the mechanical properties. Overall, this study provides for the first time a comprehensive experimental data set at organ level that leads to an improved understanding of load transfer mechanisms within the urinary bladder and serves to validate corresponding models.

Poro-viscoelastic behaviour of the zona pellucida: Impact of three-dimensional modelling on material characterisation.

The development of objective biomarkers for the qualitative assessment of oocytes prior to in-vitro fertilisation procedures is crucial, and in this respect the mechanical response of cells has already emerged as a promising and valid measure. The test setups derived from this conceptual approach usually induce complex, partly asymmetric deformation states, so that the process of material parameter identification can only be realised via three-dimensional, mathematical models. In the present study, a three-dimensional model for oocytes is proposed and implemented in the form of the finite element method. In particular, the contribution of each cellular component to the overall mechanical response is considered by including an anisotropic poro-, viscoelastic approach for the zona pellucida and an incompressible neo-Hookean material for the ooplasm. The model is calibrated and validated using experiments on porcine oocytes under plate-plate compression and indentation during quasi-static cyclic and relaxation tests. In addition to investigating the influence of glycoprotein orientation on the shape and extent of deformation, the applicability of the model to identify mechanical properties is demonstrated and discussed in relation to real, complex testing devices.

On multiscale tension-compression asymmetry in skeletal muscle.

Skeletal muscle tissue shows a clear asymmetry with regard to the passive stresses under tensile and compressive deformation, referred to as tension-compression asymmetry (TCA). The present study is the first one reporting on TCA at different length scales, associated with muscle tissue and muscle fibres, respectively. This allows for the first time the comparison of TCA between the tissue and one of its individual components, and thus to identify the length scale at which this phenomenon originates. Not only the passive stress-stretch characteristics were recorded, but also the volume changes during the axial tension and compression experiments. The study reveals clear differences in the characteristics of TCA between fibres and tissue. At tissue level TCA increases non-linearly with increasing deformation and the ratio of tensile to compressive stresses at the same magnitude of strain reaches a value of approximately 130 at 13.5% deformation. At fibre level instead it initially drops to a value of 6 and then rises again to a TCA of 14. At a deformation of 13.5%, the tensile stress is about 6 times higher. Thus, TCA is about 22 times more expressed at tissue than fibre scale. Moreover, the analysis of volume changes revealed little compressibility at tissue scale whereas at fibre level, especially under compressive stress, the volume decreases significantly. The data collected in this study suggests that the extracellular matrix has a distinct role in amplifying the TCA, and leads to more incompressible tissue behaviour. STATEMENT OF SIGNIFICANCE: This article analyses and compares for the first time the tension-compression asymmetry (TCA) displayed by skeletal muscle at tissue and fibre scale. In addition, the volume changes of tissue and fibre specimens with application of passive tensile and compressive loads are studied. The study identifies a key role of the extracellular matrix in establishing the mechanical response of skeletal muscle tissue: It contributes significantly to the passive stress, it is responsible for the major part of tissue-scale TCA and, most probably, prevents/balances the volume changes of muscle fibres during deformation. These new results thus shed light on the origin of TCA and provide new information to be used in microstructure-based approaches to model and simulate skeletal muscle tissue.

Surrogate-based Bayesian calibration of biomechanical models with isotropic material behavior.

This work introduces a computational methodology to calibrate material models in biomechanical applications under uncertainty. We adopt a Bayesian approach, which estimates the probability distributions of hyperelastic material parameters, based on force-strain measurements. We approximate the parametric biomechanical model by combining a reduced order representation of the force response with a Polynomial Chaos expansion. The surrogate model allows to employ sampling-intensive Markov chain Monte Carlo methods and provides an efficient way to estimate (generalized) Sobol coefficients. We use a Sobol sensitivity analysis to assess the influence of material parameters and present an iterative procedure to quantify the accuracy of the surrogate model as additional uncertainty during Bayesian updating. The methodology is illustrated with three cases, tensile experiments on heat-induced whey protein gel, indentation experiments for oocytes and a manufactured example. Real experimental data are used for the calibration.

Age-dependent mechanical and microstructural properties of the rabbit soleus muscle.

During growth there are serious changes in the skeletal muscles to compensate for the changed requirements in terms of body weight and size. In this study, the age-dependent (between 21 and 100 days) mechanical and microstructural properties of rabbit soleus muscle tissue were investigated. For this purpose, morphological properties (animal mass, soleus muscle mass, tibial length) were measured at 5 different times during aging. On the other hand, fibre orientation-dependent axial and semi-confined compression experiments were realised. In addition, the essential components (muscle fibres, extracellular matrix, remaining components), dominating the microstructure of muscle tissue, were analysed. While the mechanical results show hardly any age-dependent differences, the morphological and microstructural results show clear age-dependent differences. All morphological parameters increase significantly (animal mass by 839.2%, muscle mass 1050.6%, tibial length 233.6%). In contrast, microstructural parameters change differently. The percentage of fibres (divided into slow-twitch (ST) and fast-twitch (FT) fibres) increases significantly (137.6%), while the proportions of the extracellular matrix and the remaining components (48.2% and 46.1%) decrease. At the same time, the cross-sectional area of the fibres increases significantly (697.9%). The totality of this age-dependent information provides a deeper understanding of age-related changes in muscle structure and function and may contribute to successful development and validation of growth models in the future. STATEMENT OF SIGNIFICANCE: This article reports the first comprehensive data set on age-dependent morphological (animal mass, soleus muscle mass, tibial length), mechanical (axial and semi-confined compression), and microstructural (muscle fibres, extracellular matrix, remaining components) properties of the rabbit soleus muscle. On the one hand, the results of this study contribute to the understanding of muscle mechanics and thus to understanding of load transfer mechanisms inside the muscle tissue during growth. On the other hand, these results are relevant to the fields of constitutive formulation of age-dependent muscle tissue.

Architectural model for muscle growth during maturation.

Muscle architecture, which includes parameters like fascicle length, pennation angle, and physiological cross-sectional area, strongly influences skeletal muscles' mechanical properties. During maturation, the muscle architecture has to adapt to a growing organism. This study aimed to develop an architectural model capable of predicting the complete 3D fascicle architecture for primarily unipennate muscles of an arbitrary age, based on fascicle data for an initial age. For model development, we collected novel data on 3D muscle architecture of the rabbit (Oryctolagus cuniculus) M. plantaris of eight animals ranging in age from 29 to 106 days. Experimental results show that plantaris muscle belly length increases by 73%, whereas mean fascicle length and mean pennation angle increases by 39 and 14%, respectively. Those changes were incorporated into the model. In addition to the data collected for M. plantaris the predictions of the model were compared to existing literature data of rabbit M. soleus and M. gastrocnemius medialis. With an error of -1.0 ± 8.6% for relative differences in aponeurosis length, aponeurosis width, muscle height, and muscle mass, the model delivered good results matching interindividual differences. For future studies, the model could be utilized to generate realistic architectural data sets for simulation studies.

On a phase-field approach to model fracture of small intestine walls.

We address anisotropic elasticity and fracture in small intestine walls (SIWs) with both experimental and computational methods. Uniaxial tension experiments are performed on porcine SIW samples with varying alignments and quantify their nonlinear elastic anisotropic behavior. Fracture experiments on notched SIW strips reveal a high sensitivity of the crack propagation direction and the failure stress on the tissue orientation. From a modeling point of view, the observed anisotropic elastic response is studied with a continuum mechanical model stemming from a strain energy density with a neo-Hookean component and an anisotropic component with four families of fibers. Fracture is addressed with the phase-field approach, featuring two-fold anisotropy in the fracture toughness. Elastic and fracture model parameters are calibrated based on the experimental data, using the maximum and minimum limits of the experimental stress-stretch data set. A very good agreement between experimental data and computational results is obtained, the role of anisotropy being effectively captured by the proposed model in both the elastic and the fracture behavior. STATEMENT OF SIGNIFICANCE: This article reports a comprehensive experimental data set on the mechanical failure behavior of small intestinal tissue, and presents the corresponding protocols for preparing and testing the samples. On the one hand, the results of this study contribute to the understanding of small intestine mechanics and thus to understanding of load transfer mechanisms inside the tissue. On the other hand, these results are used as input for a phase-field modelling approach, presented in this article. The presented model can reproduce the mechanical failure behavior of the small intestine in an excellent way and is thus a promising tool for the future mechanical description of diseased small intestinal tissue.

Influence of layer separation on the determination of stomach smooth muscle properties.

Uniaxial tensile experiments are a standard method to determine the contractile properties of smooth muscles. Smooth muscle strips from organs of the urogenital and gastrointestinal tract contain multiple muscle layers with different muscle fiber orientations, which are frequently not separated for the experiments. During strip activation, these muscle fibers contract in deviant orientations from the force-measuring axis, affecting the biomechanical characteristics of the tissue strips. This study aimed to investigate the influence of muscle layer separation on the determination of smooth muscle properties. Smooth muscle strips, consisting of longitudinal and circumferential muscle layers (whole-muscle strips [WMS]), and smooth muscle strips, consisting of only the circumferential muscle layer (separated layer strips [SLS]), have been prepared from the fundus of the porcine stomach. Strips were mounted with muscle fibers of the circumferential layer inline with the force-measuring axis of the uniaxial testing setup. The force-length (FLR) and force-velocity relationships (FVR) were determined through a series of isometric and isotonic contractions, respectively. Muscle layer separation revealed no changes in the FLR. However, the SLS exhibited a higher maximal shortening velocity and a lower curvature factor than WMS. During WMS activation, the transversally oriented muscle fibers of the longitudinal layer shortened, resulting in a narrowing of this layer. Expecting volume constancy of muscle tissue, this narrowing leads to a lengthening of the longitudinal layer, which counteracted the shortening of the circumferential layer during isotonic contractions. Consequently, the shortening velocities of the WMS were decreased significantly. This effect was stronger at high shortening velocities.

Challenges of influencing cellular morphology by morphology engineering techniques and mechanical induced stress on filamentous pellet systems-A critical review.

Filamentous microorganisms are main producers of organic acids, enzymes, and pharmaceutical agents such as antibiotics and other active pharmaceutical ingredients. With their complex cell morphology, ranging from dispersed mycelia to dense pellets, the cultivation is challenging. In recent years, various techniques for tailor-made cell morphologies of filamentous microorganisms have been developed to increase product formation and have been summarised under the term morphology engineering. These techniques, namely microparticle-enhanced cultivation, macroparticle-enhanced cultivation, and alteration of the osmolality of the culture medium by addition of inorganic salts, the salt-enhanced cultivation, are presented and discussed in this review. These techniques have already proven to be useful and now await further proof-of-concept. Furthermore, the mechanical behaviour of individual pellets is of special interest for a general understanding of pellet mechanics and the productivity of biotechnological processes with filamentous microorganisms. Correlating them with substrate uptake and finally with productivity would be a breakthrough not to be underestimated for the comprehensive characterisation of filamentous systems. So far, this research field is under-represented. First results on filamentous pellet mechanics are discussed and important future aspects, which the filamentous expert community should deal with, will be presented and critically discussed.

Visco- and poroelastic contributions of the zona pellucida to the mechanical response of oocytes.

Probing mechanical properties of cells has been identified as a means to infer information on their current state, e.g. with respect to diseases or differentiation. Oocytes have gained particular interest, since mechanical parameters are considered potential indicators of the success of in vitro fertilisation procedures. Established tests provide the structural response of the oocyte resulting from the material properties of the cell's components and their disposition. Based on dedicated experiments and numerical simulations, we here provide novel insights on the origin of this response. In particular, polarised light microscopy is used to characterise the anisotropy of the zona pellucida, the outermost layer of the oocyte composed of glycoproteins. This information is combined with data on volumetric changes and the force measured in relaxation/cyclic, compression/indentation experiments to calibrate a multi-phasic hyper-viscoelastic model through inverse finite element analysis. These simulations capture the oocyte's overall force response, the distinct volume changes observed in the zona pellucida, and the structural alterations interpreted as a realignment of the glycoproteins with applied load. The analysis reveals the presence of two distinct timescales, roughly separated by three orders of magnitude, and associated with a rapid outflow of fluid across the external boundaries and a long-term, progressive relaxation of the glycoproteins, respectively. The new results allow breaking the overall response down into the contributions from fluid transport and the mechanical properties of the zona pellucida and ooplasm. In addition to the gain in fundamental knowledge, the outcome of this study may therefore serve an improved interpretation of the data obtained with current methods for mechanical oocyte characterisation.

Predicting muscle tissue response from calibrated component models and histology-based finite element models.

Skeletal muscle is an anisotropic soft biological tissue composed of muscle fibres embedded in a structurally complex, hierarchically organised extracellular matrix. In a recent work (Kuravi et al., 2021) we have developed 3D finite element models from series of histological sections. Moreover, based on decellularisation of fresh tissue samples, a novel set of experimental data on the direction dependent mechanical properties of collagenous ECM was established (Kohn et al., 2021). Together with existing information on the material properties of single muscle fibres, the combination of these techniques allows computing predictions of the composite tissue response. To this end, an inverse finite element procedure is proposed in the present work to calibrate a constitutive model of the extracellular matrix, and supplementary biaxial tensile tests on fresh and decellularised tissues are performed for model validation. The results of this rigorously predictive and thus unforgiving strategy suggest that the prediction of the tissue response from the individual characteristics of muscle cells and decellularised tissue is only possible within clear limits. While orders of magnitude are well matched, and the qualitative behaviour in a wide range of load cases is largely captured, the existing deviations point at potentially missing components of the model and highlight the incomplete experimental information in bottom-up multiscale approaches to model skeletal muscle tissue.

Direct measurement of the direction-dependent mechanical behaviour of skeletal muscle extracellular matrix.

This paper reports the first comprehensive data set on the anisotropic mechanical properties of isolated endo- and perimysial extracellular matrix of skeletal muscle, and presents the corresponding protocols for preparing and testing the samples. In particular, decellularisation of porcine skeletal muscle is achieved with caustic soda solution, and mechanical parameters are defined based on compressive and tensile testing in order to identify the optimal treatment time such that muscle fibres are dissolved whereas the extracellular matrix remains largely intact and mechanically functional. At around 18 h, a time window was found and confirmed by histology, in which axial tensile experiments were performed to characterise the direction-dependent mechanical response of the extracellular matrix samples, and the effect of lateral pre-compression was studied. The typical, large variability in the experimental stress response could be largely reduced by varying a single scalar factor, which was attributed to the variation of the fraction of extracellular matrix within the tissue. While experimental results on the mechanical properties of intact muscle tissue and single muscle fibres are increasingly available in literature, there is a lack of information on the properties of the collagenous components of skeletal muscle. The present work aims at closing this gap and thus contributes to an improved understanding of the mechanics of skeletal muscle tissue and provides a missing piece of information for the development of corresponding constitutive and computational models.