A cross species thermoelectric and spatiotemporal analysis of alternans in live explanted hearts using dual voltage-calcium fluorescence optical mapping.

Objective.Temperature plays a crucial role in influencing the spatiotemporal dynamics of the heart. Electrical instabilities due to specific thermal conditions typically lead to early period-doubling bifurcations and beat-to-beat alternans. These pro-arrhythmic phenomena manifest in voltage and calcium traces, resulting in compromised contractile behaviors. In such intricate scenario, dual optical mapping technique was used to uncover unexplored multi-scale and nonlinear couplings, essential for early detection and understanding of cardiac arrhythmia.Approach.We propose a methodological analysis of synchronized voltage-calcium signals for detecting alternans, restitution curves, and spatiotemporal alternans patterns under different thermal conditions, based on integral features calculation. To validate our approach, we conducted a cross-species investigation involving rabbit and guinea pig epicardial ventricular surfaces and human endocardial tissue under pacing-down protocols.Main results.We show that the proposed integral feature, as the area under the curve, could be an easily applicable indicator that may enhance the predictability of the onset and progression of cardiac alternans. Insights into spatiotemporal correlation analysis of characteristic spatial lengths across different heart species were further provided.Significance.Exploring cross-species thermoelectric features contributes to understanding temperature-dependent proarrhythmic regimes and their implications on coupled spatiotemporal voltage-calcium dynamics. The findings provide preliminary insights and potential strategies for enhancing arrhythmia detection and treatment.

Innovative Characterization of Alternans Onset and Development in Dual Voltage-Calcium Whole-Heart Optical Mapping Signals at Multiple Thermal States.

Cardiac electrical dynamics show complex space-time instabilities, like period-doubling bifurcation and beat-to-beat alternans, known to occur as pro-arrhythmic phenomena and linked to membrane voltage and intracellular calcium kinetics. Besides, cellular ionic dynamics are critically affected by temperature oscillations, further enhancing the complexity of such arrhythmias precursors that lead to irregular cardiac contraction. In this complex scenario, fluorescence dual optical mapping techniques allow the unveiling of nonlinear and multi-scale couplings. In this contribution, we propose a novel methodological analysis of synchronous dual voltage-calcium traces obtained from whole rabbit hearts for (i) detecting alternans onset and evolution, (ii) characterizing novel restitution curves, and (iii) defining spatio-temporal alternans patterns at four thermal states. We validate our approach against well-accepted analyses considering complete pacing-down restitution protocols. The proposed methodology computes integral features, e.g., area under the curve, suggesting that a novel, easy-to-use indicator, may advance predictability on alternans onset and evolution, further providing insights into spatio-temporal cardiac analyses.Clinical Relevance- This work introduces new methods for the early detection of cardiac alternans onset and development as precursors of arrhythmias and fibrillation at different temperatures.

A Simulation Study of the Effects of His Bundle Pacing in Left Bundle Branch Block.

His bundle pacing (HBP) has emerged as a feasible alternative to right (RVP) and biventricular pacing (BVP) for Cardiac Resynchronization Therapy (CRT). This study sought to assess, in ex-vivo experimental models, the optimal setup for HBP in terms of electrode placement and pacing protocol to achieve superior electrical synchrony in the case of complete His-Purkinje block and left bundle branch block (LBBB). We developed a 3D model of His bundle and bundle branches, embedded in a patient-specific biventricular heart model reconstructed from CT images. A monodomain reaction-diffusion model was adopted to describe the propagation of cardiac action potential, and a custom procedure was developed to compute pseudo-ECGs. Experimental measurements of tip electrode potential waveforms have been performed on ex-vivo swine myocardium to determine the appropriate boundary condition for delivering the electrical stimulus in the numerical model. An extended parametric analysis, investigating the effect of the electrode orientation and helix length, pacing protocol, and atrioventricular delay, allowed us to determine the optimal setup for HBP therapy. Both selective (S-HBP) and non-selective (NS-HBP) His bundle pacing were tested, as the variable anatomical location of the His bundle can result in the activation of the surrounding myocardium. Our study indicates a perpendicular placement of the electrode as the most advantageous for restoring the physiological function of the His-Purkinje system. We found that higher-energy protocols can compensate for the effects of an angled placement though concurring to potential tip fibrosis. Promisingly, we also revealed that an increased electrode helix length can provide optimal resynchronization even with low-energy pacing protocols. Our results provide informative guidance for implant procedure and therapy optimization, which will hopefully have clinical implications further improving the procedural success rates and patients' quality of life, due to reduced incidence of lead revision and onset of complications.

Biomechanical constitutive modeling of the gastrointestinal tissues: a systematic review.

The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are characterized by a biomechanical constitutive model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract. Here, a systematic review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies.

A Soft and Skin-Interfaced Smart Patch Based on Fiber Optics for Cardiorespiratory Monitoring.

Wearables are valuable solutions for monitoring a variety of physiological parameters. Their application in cardiorespiratory monitoring may significantly impact global health problems and the economic burden related to cardiovascular and respiratory diseases. Here, we describe a soft biosensor capable of monitoring heart (HR) and respiratory (RR) rates simultaneously. We show that a skin-interfaced biosensor based on fiber optics (i.e., the smart patch) is capable of estimating HR and RR by detecting local ribcage strain caused by breathing and heart beating. The system addresses some of the main technical challenges that limit the wide-scale use of wearables, such as the simultaneous monitoring of HR and RR via single sensing modalities, their limited skin compliance, and low sensitivity. We demonstrate that the smart patch estimates HR and RR with high fidelity under different respiratory conditions and common daily body positions. We highlight the system potentiality of real-time cardiorespiratory monitoring in a broad range of home settings.

Osteolytic vs. Osteoblastic Metastatic Lesion: Computational Modeling of the Mechanical Behavior in the Human Vertebra after Screws Fixation Procedure.

Metastatic lesions compromise the mechanical integrity of vertebrae, increasing the fracture risk. Screw fixation is usually performed to guarantee spinal stability and prevent dramatic fracture events. Accordingly, predicting the overall mechanical response in such conditions is critical to planning and optimizing surgical treatment. This work proposes an image-based finite element computational approach describing the mechanical behavior of a patient-specific instrumented metastatic vertebra by assessing the effect of lesion size, location, type, and shape on the fracture load and fracture patterns under physiological loading conditions. A specific constitutive model for metastasis is integrated to account for the effect of the diseased tissue on the bone material properties. Computational results demonstrate that size, location, and type of metastasis significantly affect the overall vertebral mechanical response and suggest a better way to account for these parameters in estimating the fracture risk. Combining multiple osteolytic lesions to account for the irregular shape of the overall metastatic tissue does not significantly affect the vertebra fracture load. In addition, the combination of loading mode and metastasis type is shown for the first time as a critical modeling parameter in determining fracture risk. The proposed computational approach moves toward defining a clinically integrated tool to improve the management of metastatic vertebrae and quantitatively evaluate fracture risk.

Multiscale and Multiphysics Modeling of Anisotropic Cardiac RFCA: Experimental-Based Model Calibration via Multi-Point Temperature Measurements.

Radiofrequency catheter ablation (RFCA) is the mainstream treatment for drug-refractory cardiac fibrillation. Multiple studies demonstrated that incorrect dosage of radiofrequency energy to the myocardium could lead to uncontrolled tissue damage or treatment failure, with the consequent need for unplanned reoperations. Monitoring tissue temperature during thermal therapy and predicting the extent of lesions may improve treatment efficacy. Cardiac computational modeling represents a viable tool for identifying optimal RFCA settings, though predictability issues still limit a widespread usage of such a technology in clinical scenarios. We aim to fill this gap by assessing the influence of the intrinsic myocardial microstructure on the thermo-electric behavior at the tissue level. By performing multi-point temperature measurements on ex-vivo swine cardiac tissue samples, the experimental characterization of myocardial thermal anisotropy allowed us to assemble a fine-tuned thermo-electric material model of the cardiac tissue. We implemented a multiphysics and multiscale computational framework, encompassing thermo-electric anisotropic conduction, phase-lagging for heat transfer, and a three-state dynamical system for cellular death and lesion estimation. Our analysis resulted in a remarkable agreement between ex-vivo measurements and numerical results. Accordingly, we identified myocardium anisotropy as the driving effect on the outcomes of hyperthermic treatments. Furthermore, we characterized the complex nonlinear couplings regulating tissue behavior during RFCA, discussing model calibration, limitations, and perspectives.

Optical Ultrastructure of Large Mammalian Hearts Recovers Discordant Alternans by In Silico Data Assimilation.

Understanding and predicting the mechanisms promoting the onset and sustainability of cardiac arrhythmias represent a primary concern in the scientific and medical communities still today. Despite the long-lasting effort in clinical and physico-mathematical research, a critical aspect to be fully characterized and unveiled is represented by spatiotemporal alternans patterns of cardiac excitation. The identification of discordant alternans and higher-order alternating rhythms by advanced data analyses as well as their prediction by reliable mathematical models represents a major avenue of research for a broad and multidisciplinary scientific community. Current limitations concern two primary aspects: 1) robust and general-purpose feature extraction techniques and 2) in silico data assimilation within reliable and predictive mathematical models. Here, we address both aspects. At first, we extend our previous works on Fourier transformation imaging (FFI), applying the technique to whole-ventricle fluorescence optical mapping. Overall, we identify complex spatial patterns of voltage alternans and characterize higher-order rhythms by a frequency-series analysis. Then, we integrate the optical ultrastructure obtained by FFI analysis within a fine-tuned electrophysiological mathematical model of the cardiac action potential. We build up a novel data assimilation procedure demonstrating its reliability in reproducing complex alternans patterns in two-dimensional computational domains. Finally, we prove that the FFI approach applied to both experimental and simulated signals recovers the same information, thus closing the loop between the experiment, data analysis, and numerical simulations.

A space-fractional bidomain framework for cardiac electrophysiology: 1D alternans dynamics.

Cardiac electrophysiology modeling deals with a complex network of excitable cells forming an intricate syncytium: the heart. The electrical activity of the heart shows recurrent spatial patterns of activation, known as cardiac alternans, featuring multiscale emerging behavior. On these grounds, we propose a novel mathematical formulation for cardiac electrophysiology modeling and simulation incorporating spatially non-local couplings within a physiological reaction-diffusion scenario. In particular, we formulate, a space-fractional electrophysiological framework, extending and generalizing similar works conducted for the monodomain model. We characterize one-dimensional excitation patterns by performing an extended numerical analysis encompassing a broad spectrum of space-fractional derivative powers and various intra- and extracellular conductivity combinations. Our numerical study demonstrates that (i) symmetric properties occur in the conductivity parameters' space following the proposed theoretical framework, (ii) the degree of non-local coupling affects the onset and evolution of discordant alternans dynamics, and (iii) the theoretical framework fully recovers classical formulations and is amenable for parametric tuning relying on experimental conduction velocity and action potential morphology.

Thermal effects on cardiac alternans onset and development: A spatiotemporal correlation analysis.

Alternans of cardiac action potential duration represent critical precursors for the development of life-threatening arrhythmias and sudden cardiac death. The system's thermal state affects these electrical disorders requiring additional theoretical and experimental efforts to improve a patient-specific clinical understanding. In such a scenario, we generalize a recent work from Loppini et al. [Phys. Rev. E 100, 020201(R) (2019)PREHBM2470-004510.1103/PhysRevE.100.020201] by performing an extended spatiotemporal correlation study. We consider high-resolution optical mapping recordings of canine ventricular wedges' electrical activity at different temperatures and pacing frequencies. We aim to recommend the extracted characteristic length as a potential predictive index of cardiac alternans onset and evolution within a wide range of system states. In particular, we show that a reduction of temperature results in a drop of the characteristic length, confirming the impact of thermal instabilities on cardiac dynamics. Moreover, we theoretically investigate the use of such an index to identify and predict different alternans regimes. Finally, we propose a constitutive phenomenological law linking conduction velocity, characteristic length, and temperature in view of future numerical investigations.

Effect of pedicle screw angles on the fracture risk of the human vertebra: A patient-specific computational model.

The assessment of a human vertebra's stability after a screws fixation procedure and its fracture risk is still an open clinical problem. The accurate evaluation of fracture risk requires that all fracture mechanical determinants such as geometry, constitutive behavior, loading modes, and screws angulation are accounted for, which requires biomechanics-based analyses. As such, in the present work we investigate the effect of pedicle screws angulation on a patient-specific model of non osteoporotic lumbar vertebra, derived from clinical CT images. We propose a novel computational approach of fracture analysis and compare the effects of fixation stability in the lumbar spine. We considered a CT-based three-dimensional FE model of bilaterally instrumented L4 vertebra virtually implanting pedicle screws according to clinical guidelines. Nine screws trajectories were selected combining three craniocaudal and mediolateral angles, thus investigated through a parametric computational analysis. Bone was modeled as an elastic material with element-wise inhomogeneous properties fine-tuned on CT data. We implemented a custom algorithm to identify the thin cortical layer correctly from CT images ensuring reliable material properties in the computational model. Physiological motion (i.e., flexion, extension, axial rotation, lateral bending) was further accomplished by simultaneously loading the vertebra and the implant. We simulated local progressive damage of the bone by using a quasi-static force-driven incremental approach and considering a stress-based fracture criterion. Ductile-like and brittle-like fractures were found. Statistical analyses show significant differences comparing screws trajectories and averaging the results among six loading modes. In particular, we identified the caudomedial trajectory as the least critical case, thus safer from a clinical perspective. Instead, medial and craniolaterally oriented screws entailed higher peak and average stresses, though no statistical evidence classified such loads as the most critical scenarios. A quantitative validation procedure will be required in the future to translate our findings into clinical practice. Besides, to apply the results to the target osteoporotic population, new studies will be needed, including a specimen from an osteoporotic patient and the effect of osteoporosis on the constitutive model of bone.

In-silico study of the cardiac arrhythmogenic potential of biomaterial injection therapy.

Biomaterial injection is a novel therapy to treat ischemic heart failure (HF) that has shown to reduce remodeling and restore cardiac function in recent preclinical studies. While the effect of biomaterial injection in reducing mechanical wall stress has been recently demonstrated, the influence of biomaterials on the electrical behavior of treated hearts has not been elucidated. In this work, we developed computational models of swine hearts to study the electrophysiological vulnerability associated with biomaterial injection therapy. The propagation of action potentials on realistic biventricular geometries was simulated by numerically solving the monodomain electrophysiology equations on anatomically-detailed models of normal, HF untreated, and HF treated hearts. Heart geometries were constructed from high-resolution magnetic resonance images (MRI) where the healthy, peri-infarcted, infarcted and gel regions were identified, and the orientation of cardiac fibers was informed from diffusion-tensor MRI. Regional restitution properties in each case were evaluated by constructing a probability density function of the action potential duration (APD) at different cycle lengths. A comparative analysis of the ventricular fibrillation (VF) dynamics for every heart was carried out by measuring the number of filaments formed after wave braking. Our results suggest that biomaterial injection therapy does not affect the regional dispersion of repolarization when comparing untreated and treated failing hearts. Further, we found that the treated failing heart is more prone to sustain VF than the normal heart, and is at least as susceptible to sustained VF as the untreated failing heart. Moreover, we show that the main features of VF dynamics in a treated failing heart are not affected by the level of electrical conductivity of the biogel injectates. This work represents a novel proof-of-concept study demonstrating the feasibility of computer simulations of the heart in understanding the arrhythmic behavior in novel therapies for HF.

An orthotropic electro-viscoelastic model for the heart with stress-assisted diffusion.

We propose and analyse the properties of a new class of models for the electromechanics of cardiac tissue. The set of governing equations consists of nonlinear elasticity using a viscoelastic and orthotropic exponential constitutive law, for both active stress and active strain formulations of active mechanics, coupled with a four-variable phenomenological model for human cardiac cell electrophysiology, which produces an accurate description of the action potential. The conductivities in the model of electric propagation are modified according to stress, inducing an additional degree of nonlinearity and anisotropy in the coupling mechanisms, and the activation model assumes a simplified stretch-calcium interaction generating active tension or active strain. The influence of the new terms in the electromechanical model is evaluated through a sensitivity analysis, and we provide numerical validation through a set of computational tests using a novel mixed-primal finite element scheme.

Spatiotemporal correlation uncovers characteristic lengths in cardiac tissue.

Complex spatiotemporal patterns of action potential duration have been shown to occur in many mammalian hearts due to period-doubling bifurcations that develop with increasing frequency of stimulation. Here, through high-resolution optical mapping experiments and mathematical modeling, we introduce a characteristic spatial length of cardiac activity in canine ventricular wedges via a spatiotemporal correlation analysis, at different stimulation frequencies and during fibrillation. We show that the characteristic length ranges from 40 to 20 cm during one-to-one responses and it decreases to a specific value of about 3 cm at the transition from period-doubling bifurcation to fibrillation. We further show that during fibrillation, the characteristic length is about 1 cm. Another significant outcome of our analysis is the finding of a constitutive phenomenological law obtained from a nonlinear fitting of experimental data which relates the conduction velocity restitution curve with the characteristic length of the system. The fractional exponent of 3/2 in our phenomenological law is in agreement with the domain size remapping required to reproduce experimental fibrillation dynamics within a realistic cardiac domain via accurate mathematical models.

Mechanical behavior of metastatic femurs through patient-specific computational models accounting for bone-metastasis interaction.

This paper proposes a computational model based on a finite-element formulation for describing the mechanical behavior of femurs affected by metastatic lesions. A novel geometric/constitutive description is introduced by modelling healthy bone and metastases via a linearly poroelastic constitutive approach. A Gaussian-shaped graded transition of material properties between healthy and metastatic tissues is prescribed, in order to account for the bone-metastasis interaction. Loading-induced failure processes are simulated by implementing a progressive damage procedure, formulated via a quasi-static displacement-driven incremental approach, and considering both a stress- and a strain-based failure criterion. By addressing a real clinical case, left and right patient-specific femur models are geometrically reconstructed via an ad-hoc imaging procedure and embedding multiple distributions of metastatic lesions along femurs. Significant differences in fracture loads, fracture mechanisms, and damage patterns, are highlighted by comparing the proposed constitutive description with a purely elastic formulation, where the metastasis is treated as a pseudo-healthy tissue or as a void region. Proposed constitutive description allows to capture stress/strain localization mechanisms within the metastatic tissue, revealing the model capability in describing possible strain-induced mechano-biological stimuli driving onset and evolution of the lesion. The proposed approach opens towards the definition of effective computational strategies for supporting clinical decision and treatments regarding metastatic femurs, contributing also to overcome some limitations of actual standards and procedures.

Competing Mechanisms of Stress-Assisted Diffusivity and Stretch-Activated Currents in Cardiac Electromechanics.

We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

Postbariatric Brachioplasty with Posteromedial Scar: Physical Model, Technical Refinements, and Clinical Outcomes.

BACKGROUND: Brachioplasty is an increasingly performed procedure following massive weight loss. A visible scar is the main hindrance to this surgery. The aims of the study were to develop a physical model to investigate the ideal location of the surgical incision and to present the authors' technical refinements with the posteromedial scar approach. METHODS: Twenty-four postbariatric patients underwent brachioplasty with posteromedial scar placement, concomitant liposuction, fascial plication, and axillary Z-plasty. Skin specimens were tested and a physical model of the arm was set up to investigate the difference in mechanical stress on the posteromedial and medial scars. The validated Patient and Observer Scar Assessment Scale, the Vancouver Scar Scale, and a questionnaire assessing subjective improvements were administered to patients. Preoperative and postoperative photographs were assessed by three independent plastic surgeons. RESULTS: The physical model showed that stress intensity and distribution along the scar were reduced in the posteromedial location, with smaller scar displacement in the loading simulations. Twenty-three patients healed uneventfully. One (4.1 percent) had a 2-cm dehiscence. Mean Patient and Observer Scar Assessment Scale scores were, respectively, 2 ± 0.76 and 2.13 ± 0.64 in the patients' and observers' questionnaires. The mean Vancouver Scar Scale value was 3.5 ± 1.7. Questionnaires assessing the subjective outcomes showed a mean value of 3.45 ± 0.63 of 4. The surgeons' assessment resulted in a score of 4.5 ± 0.4 of 5. CONCLUSIONS: The physical model demonstrated that the posteromedial scar was subjected to lower mechanical stress and displacement. The reported technical refinements allowed pleasant arm recontouring to be achieved with acceptable scarring and a low incidence of complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A note on stress-driven anisotropic diffusion and its role in active deformable media.

We introduce a new model to describe diffusion processes within active deformable media. Our general theoretical framework is based on physical and mathematical considerations, and it suggests to employ diffusion tensors directly influenced by the coupling with mechanical stress. The proposed generalised reaction-diffusion-mechanics model reveals that initially isotropic and homogeneous diffusion tensors turn into inhomogeneous and anisotropic quantities due to the intrinsic structure of the nonlinear coupling. We study the physical properties leading to these effects, and investigate mathematical conditions for its occurrence. Together, the mathematical model and the numerical results obtained using a mixed-primal finite element method, clearly support relevant consequences of stress-driven diffusion into anisotropy patterns, drifting, and conduction velocity of the resulting excitation waves. Our findings also indicate the applicability of this novel approach in the description of mechano-electric feedback in actively deforming bio-materials such as the cardiac tissue.

A FSI computational framework for vascular physiopathology: A novel flow-tissue multiscale strategy.

A novel fluid-structure computational framework for vascular applications is herein presented. It is developed by combining the double multi-scale nature of vascular physiopathology in terms of both tissue properties and blood flow. Addressing arterial tissues, they are modelled via a nonlinear multiscale constitutive rationale, based only on parameters having a clear histological and biochemical meaning. Moreover, blood flow is described by coupling a three-dimensional fluid domain (undergoing physiological inflow conditions) with a zero-dimensional model, which allows to reproduce the influence of the downstream vasculature, furnishing a realistic description of the outflow proximal pressure. The fluid-structure interaction is managed through an explicit time-marching approach, able to accurately describe tissue nonlinearities within each computational step for the fluid problem. A case study associated to a patient-specific aortic abdominal aneurysmatic geometry is numerically investigated, highlighting advantages gained from the proposed multiscale strategy, as well as showing soundness and effectiveness of the established framework for assessing useful clinical quantities and risk indexes.

Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device.

This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.