Universität Stuttgart
Permanent URI for this communityhttps://elib.uni-stuttgart.de/handle/11682/1
Browse
13 results
Search Results
Item Open Access Linking cortex and contraction : integrating models along the corticomuscular pathway(2023) Haggie, Lysea; Schmid, Laura; Röhrle, Oliver; Besier, Thor; McMorland, Angus; Saini, HarnoorComputational models of the neuromusculoskeletal system provide a deterministic approach to investigate input-output relationships in the human motor system. Neuromusculoskeletal models are typically used to estimate muscle activations and forces that are consistent with observed motion under healthy and pathological conditions. However, many movement pathologies originate in the brain, including stroke, cerebral palsy, and Parkinson’s disease, while most neuromusculoskeletal models deal exclusively with the peripheral nervous system and do not incorporate models of the motor cortex, cerebellum, or spinal cord. An integrated understanding of motor control is necessary to reveal underlying neural-input and motor-output relationships. To facilitate the development of integrated corticomuscular motor pathway models, we provide an overview of the neuromusculoskeletal modelling landscape with a focus on integrating computational models of the motor cortex, spinal cord circuitry, α-motoneurons and skeletal muscle in regard to their role in generating voluntary muscle contraction. Further, we highlight the challenges and opportunities associated with an integrated corticomuscular pathway model, such as challenges in defining neuron connectivities, modelling standardisation, and opportunities in applying models to study emergent behaviour. Integrated corticomuscular pathway models have applications in brain-machine-interaction, education, and our understanding of neurological disease.Item Open Access Autonomous adaption of intelligent humidity‐programmed hydrogel patches for tunable stiffness and drug release(2023) Pflumm, Stephan; Wiedemann, Yvonne; Fauser, Dominik; Safaraliyev, Javidan; Lunter, Dominique; Steeb, Holger; Ludwigs, SabineIntelligent humidity‐programmed hydrogel patches with high stretchability and tunable water‐uptake and ‐release are prepared by copolymerization and crosslinking of N‐isopropylacrylamide and oligo(ethylene glycol) comonomers. These intelligent elastomeric patches strongly respond to different humidities and temperatures in terms of mechanical properties which makes them applicable for soft robotics and smart skin applications where autonomous adaption to environmental conditions is a key requirement. It is shown that beyond using the hydrogel in the conventional state in aqueous media, new patches can be controlled by relative humidity. This humidity programming of the patches allows to tune drug release kinetics, opening potential application fields such as skin wound therapy and personalized medication. In situ dynamic‐mechanical measurements show a huge dependence on temperature and humidity. The glass transition temperature Tg shifts from around 60 °C at dry conditions to below 0 °C for 75% r.h. and higher. The storage modulus is tunable over more than four orders of magnitude from 0.6 up to 400 MPa. Time‐temperature superposition in master curves allows to extract relaxation times over 14 orders of magnitude. With strains at break of over 200% the patches are compliant with human skin and therefore patient‐friendly in terms of adapting to movements.Item Open Access Patient‐specific simulation of brain tumour growth and regression(2023) Suditsch, Marlon; Ricken, Tim; Wagner, ArndtThe medical relevance of brain tumours is characterised by its locally invasive and destructive growth. With a high mortality rate combined with a short remaining life expectancy, brain tumours are identified as highly malignant. A continuum‐mechanical model for the description of the governing processes of growth and regression is derived in the framework of the Theory of Porous Media (TPM). The model is based on medical multi‐modal magnetic resonance imaging (MRI) scans, which represent the gold standard in diagnosis. The multi‐phase model is described mathematically via strongly coupled partial differential equations. This set of governing equations is transformed into their weak formulation and is solved with the software package FEniCS. A proof‐of‐concept simulation based on one patient geometry and tumour pathology shows the relevant processes of tumour growth and the results are discussed.Item Open Access Improving the accuracy of musculotendon models for the simulation of active lengthening(2023) Millard, Matthew; Kempter, Fabian; Stutzig, Norman; Siebert, Tobias; Fehr, JörgVehicle accidents can cause neck injuries which are costly for individuals and society. Safety systems could be designed to reduce the risk of neck injury if it were possible to accurately simulate the tissue-level injuries that later lead to chronic pain. During a crash, reflexes cause the muscles of the neck to be actively lengthened. Although the muscles of the neck are often only mildly injured, the forces developed by the neck’s musculature affect the tissues that are more severely injured. In this work, we compare the forces developed by MAT_156, LS-DYNA’s Hill-type model, and the newly proposed VEXAT muscle model during active lengthening. The results show that Hill-type muscle models underestimate forces developed during active lengthening, while the VEXAT model can more faithfully reproduce experimental measurements.Item Open Access Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol(2021) Hellwig, Christian T.; Delgado, M. Eugenia; Skoko, Josip; Dyck, Lydia; Hanna, Carol; Wentges, Alexa; Langlais, Claudia; Hagenlocher, Cathrin; Mack, Alexandra; Dinsdale, David; Cain, Kelvin; MacFarlane, Marion; Rehm, MarkusCancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.Item Open Access Analysing the bone cement flow in the injection apparatus during vertebroplasty(2023) Trivedi, Zubin; Gehweiler, Dominic; Wychowaniec, Jacek K.; Ricken, Tim; Gueorguiev-Rüegg, Boyko; Wagner, Arndt; Röhrle, OliverVertebroplasty, a medical procedure for treating vertebral fractures, requires medical practitioners to inject bone cement inside the vertebra using a cannula attached to a syringe. The required injection force must be small enough for the practitioner to apply it by hand while remaining stable for a controlled injection. Several factors could make the injection force unintuitive for the practitioners, one of them being the non‐Newtonian nature of the bone cement. The viscosity of the bone cement varies as it flows through the different parts of the injection apparatus and the porous cancellous interior of the vertebra. Therefore, it is important to study the flow of bone cement through these parts. This work is a preliminary study on the flow of bone cement through the injection apparatus. Firstly, we obtained the rheological parameters for the power law model of bone cement using experiments using standard clinical equipment. These parameters were then used to obtain the shear rate, viscosity, and velocity profiles of the bone cement flow through the cannula. Lastly, an analysis was carried out to understand the influence of various geometrical parameters of the injection apparatus, in which the radius of the cannula was found to be the most influential parameter.Item Open Access An investigation of tendon strains in jersey finger injury load cases using a finite element neuromuscular human body model(2023) Nölle, Lennart V.; Alfaro, Eduardo Herrera; Martynenko, Oleksandr V.; Schmitt, SynIntroduction: A common hand injury in American football, rugby and basketball is the so-called jersey finger injury (JFI), in which an eccentric overextension of the distal interphalangeal joint leads to an avulsion of the connected musculus flexor digitorum profundus (FDP) tendon. In the field of automotive safety assessment, finite element (FE) neuromuscular human body models (NHBMs) have been validated and are employed to evaluate different injury types related to car crash scenarios. The goal of this study is to show, how such a model can be modified to assess JFIs by adapting the hand of an FE-NHBM for the computational analysis of tendon strains during a generalized JFI load case. Methods: A jersey finger injury criterion (JFIC) covering the injury mechanisms of tendon straining and avulsion was defined based on biomechanical experiments found in the literature. The hand of the Total Human Model for Safety (THUMS) version 3.0 was combined with the musculature of THUMS version 5.03 to create a model with appropriate finger mobility. Muscle routing paths of FDP and musculus flexor digitorum superficialis (FDS) as well as tendon material parameters were optimized using literature data. A simplified JFI load case was simulated as the gripping of a cylindrical rod with finger flexor activation levels between 0% and 100%, which was then retracted with the velocity of a sprinting college football player to forcefully open the closed hand. Results: The optimization of the muscle routing node positions and tendon material parameters yielded good results with minimum normalized mean absolute error values of 0.79% and 7.16% respectively. Tendon avulsion injuries were detected in the middle and little finger for muscle activation levels of 80% and above, while no tendon or muscle strain injuries of any kind occurred. Discussion: The presented work outlines the steps necessary to adapt the hand model of a FE-NHBM for the assessment of JFIs using a newly defined injury criterion called the JFIC. The injury assessment results are in good agreement with documented JFI symptoms. At the same time, the need to rethink commonly asserted paradigms concerning the choice of muscle material parameters is highlighted.Item Open Access Multi-scale mechanobiological model for skeletal muscle hypertrophy(2022) Villota Narvaez, Yesid Alexis; Garzón-Alvarado, Diego A.; Röhrle, Oliver; Ramírez-Martínez, Angelica M.Skeletal muscle adaptation is correlated to training exercise by triggering different signaling pathways that target many functions; in particular, the IGF1-AKT pathway controls protein synthesis and degradation. These two functions regulate the adaptation in size and strength of muscles. Computational models for muscle adaptation have focused on: the biochemical description of signaling pathways or the mechanical description of muscle function at organ scale; however, an interrelation between these two models should be considered to understand how an adaptation in muscle size affects the protein synthesis rate. In this research, a dynamical model for the IGF1-AKT signaling pathway is linked to a continuum-mechanical model describing the active and passive mechanical response of a muscle; this model is used to study the impact of the adaptive muscle geometry on the protein synthesis at the fiber scale. This new computational model links the signaling pathway to the mechanical response by introducing a growth tensor, and links the mechanical response to the signaling pathway through the evolution of the protein synthesis rate. The predicted increase in cross sectional area (CSA) due to an 8 weeks training protocol excellently agreed with experimental data. Further, our results show that muscle growth rate decreases, if the correlation between protein synthesis and CSA is negative. The outcome of this study suggests that multi-scale models coupling continuum mechanical properties and molecular functions may improve muscular therapies and training protocols.Item Open Access Active exoskeleton reduces erector spinae muscle activity during lifting(2023) Walter, Tobias; Stutzig, Norman; Siebert, TobiasMusculoskeletal disorders (MSD) are a widespread problem, often regarding the lumbar region. Exoskeletons designed to support the lower back could be used in physically demanding professions with the intention of reducing the strain on the musculoskeletal system, e.g., by lowering task-related muscle activation. The present study aims to investigate the effect of an active exoskeleton on back muscle activity when lifting weights. Within the framework of the study, 14 subjects were asked to lift a 15 kg box with and without an active exoskeleton which allows the adjustment of different levels of support, while the activity of their M. erector spinae (MES) was measured using surface electromyography. Additionally, the subjects were asked about their overall rating of perceived exertion (RPE) during lifting under various conditions. Using the exoskeleton with the maximum level of support, the muscle activity was significantly lower than without exoskeleton. A significant correlation was found between the exoskeleton’s support level and the reduction of MES activity. The higher the support level, the lower the observed muscle activity. Furthermore, when lifting with the maximum level of support, RPE was found to be significantly lower than without exoskeleton too. A reduction in the MES activity indicates actual support for the movement task and might indicate lower compression forces in the lumbar region. It is concluded that the active exoskeleton supports people noticeably when lifting heavy weights. Exoskeletons seem to be a powerful tool for reducing load during physically demanding jobs and thus, their use might be helpful in lowering the risk of MSD.Item Open Access Convergence of pathway analysis and pattern recognition predicts sensitization to latest generation TRAIL therapeutics by IAP antagonism(2020) Vetma, Vesna; Guttà, Cristiano; Peters, Nathalie; Praetorius, Christian; Hutt, Meike; Seifert, Oliver; Meier, Friedegund; Kontermann, Roland; Kulms, Dagmar; Rehm, MarkusSecond generation TRAIL-based therapeutics, combined with sensitising co-treatments, have recently entered clinical trials. However, reliable response predictors for optimal patient selection are not yet available. Here, we demonstrate that a novel and translationally relevant hexavalent TRAIL receptor agonist, IZI1551, in combination with Birinapant, a clinically tested IAP antagonist, efficiently induces cell death in various melanoma models, and that responsiveness can be predicted by combining pathway analysis, data-driven modelling and pattern recognition. Across a panel of 16 melanoma cell lines, responsiveness to IZI1551/Birinapant was heterogeneous, with complete resistance and pronounced synergies observed. Expression patterns of TRAIL pathway regulators allowed us to develop a combinatorial marker that predicts potent cell killing with high accuracy. IZI1551/Birinapant responsiveness could be predicted not only for cell lines, but also for 3D tumour cell spheroids and for cells directly isolated from patient melanoma metastases (80-100% prediction accuracies). Mathematical parameter reduction identified 11 proteins crucial to ensure prediction accuracy, with x-linked inhibitor of apoptosis protein (XIAP) and procaspase-3 scoring highest, and Bcl-2 family members strongly represented. Applied to expression data of a cohort of n = 365 metastatic melanoma patients in a proof of concept in silico trial, the predictor suggested that IZI1551/Birinapant responsiveness could be expected for up to 30% of patient tumours. Overall, response frequencies in melanoma models were very encouraging, and the capability to predict melanoma sensitivity to combinations of latest generation TRAIL-based therapeutics and IAP antagonists can address the need for patient selection strategies in clinical trials based on these novel drugs.