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Item Accurate simulation of cuff electrode stimulation predicting in-vivo strength-duration thresholds(Wiley, 2022) Lazorchak, Nathaniel; Horn, M. Ryne; Muzquiz, M. Ivette; Mintch, Landan M.; Yoshida, Ken; Biomedical Engineering, School of Engineering and TechnologyBackground: In-silico experiments used to optimize and inform how peripheral nerve based electrode designs perform hold the promise of greatly reducing the guesswork with new designs as well as the number of animals used to identify and prove promising designs. Given adequate realism, in-silico experiments offer the promise of identifying putative mechanisms that further inform exploration of novel stimulation and recording techniques and their interactions with bioelectric phenomena. However, despite using validated nerve fiber models, when applied to the more complex case of an implanted extracellular electrode, the in-silico experiments often do not compare quantitatively with the results of experiments conducted in in-vivo experiments. This suggests that the accuracy/realism of the environment and the lamination of the nerve bundle plays an important role in this discrepancy. This paper describes the sensitivity of in-silico models to the electrical parameter estimates and volume conductor type used. Methods: In-vivo work was performed on rat vagus nerves (N = 2) to characterize the strength-duration curve for various peaks identified in a compound nerve action potential (CAP) measured via a needle electrode. The vagus nerve has several distinct populations of nerve fiber calibers and types. Recruitment of a fiber caliber/type generates distinct peaks that can be identified, and whose conduction delay correlates to a conduction velocity. Peaks were identified by their recruitment thresholds and associated to their conduction velocities by the conduction delays of their peaks. An in-silico analog of the in-vivo experiment was constructed and experiments were run at the two extreme volume conductor cases: (1) The nerve in-saline, and (2) the nerve in-air. The specifically targeted electrical parameters were extraneural environment (in-air versus saline submersion), the resistivity (ρ) of the epineurium and perineurium, and the relative permittivity (εr ) of those same tissues. A time varying finite element method (FEM) model of the potential distribution vs time was quantified and projected onto a modified McIntyre, Richardson, and Grill (MRG), myelinated spinal nerve, active fiber model in NEURON to identify the threshold of activation as a function of stimulus pulse amplitude versus pulse width versus fiber diameter. The in-silico results were then compared to the in-vivo results. Results: The finite element method simulations spanned two macro environments: in-saline and in-air. For these environments, the resistivities for low and high frequencies as well as two different permittivity cases were used. Between these 8 cases unique cases it was found that the most accurate combination of those variables was the in-air environment for low-frequency resistivity (ρ0 ) and ex-vivo a measured permittivity (εr,measured ) from unpublished ex-vivo experiments in canine vagal nerve, achieving a high degree of convergence (r2 = 0.96). As the in-vivo work was conducted in in-air, the in-air boundary condition test case was convergent with the in-silico results. Conclusions: The results of this investigation suggest that increasing realism in simulations begets more accurate predictions. Of particular importance are (ρ) and extraneural environment, with reactive electrical parameters becoming important for input waveforms with energy in higher frequencies.Item Cellular Helmet Liner Design through Bio-inspired Structures and Topology Optimization of Compliant Mechanism Lattices(SAE International, 2018-12-28) Najmon, Joel; DeHart, Jacob; Wood, Zebulun; Tovar, Andres; Department of Mechanical Engineering, School of Engineering and TechnologyThe continuous development of sport technologies constantly demands advancements in protective headgear to reduce the risk of head injuries. This article introduces new cellular helmet liner designs through two approaches. The first approach is the study of energy-absorbing biological materials. The second approach is the study of lattices comprised of force-diverting compliant mechanisms. On the one hand, bio-inspired liners are generated through the study of biological, hierarchical materials. An emphasis is given on structures in nature that serve similar concussion-reducing functions as a helmet liner. Inspiration is drawn from organic and skeletal structures. On the other hand, compliant mechanism lattice (CML)-based liners use topology optimization to synthesize rubber cellular unit cells with effective positive and negative Poisson's ratios. Three lattices are designed using different cellular unit cell arrangements, namely, all positive, all negative, and alternating effective Poisson's ratios. The proposed cellular (bio-inspired and CML-based) liners are embedded between two polycarbonate shells, thereby, replacing the traditional expanded polypropylene foam liner used in standard sport helmets. The cellular liners are analyzed through a series of 2D extruded ballistic impact simulations to determine the best performing liner topology and its corresponding rubber hardness. The cellular design with the best performance is compared against an expanded polypropylene foam liner in a 3D simulation to appraise its protection capabilities and verify that the 2D extruded design simulations scale to an effective 3D design.Item Computational fluid dynamics analysis of the upper airway after rapid maxillary expansion: a case report(SpringerOpen, 2015-05-24) Ghoneima, Ahmed; AlBarakati, Sahar; Jiang, Feifei; Kula, Katherine; Wasfy, Tamer; Department of Orthodontics and Oral Facial Genetics, IU School of DentistryBACKGROUND: Assessment of the upper airway volume, morphology, and mechanics is of great importance for the orthodontic patient. We hypothesize that upper airway dimensions have significant effects on the dynamics of the airway flow and that both the dimensions and mechanics of the upper airway are greatly affected by orthodontic and orthopedic procedures such as rapid maxillary expansion (RME). The aim of the current study was to assess the effect of RME on the airway flow rate and pattern by comparing the fluid dynamics results of pre- and post-treatment finite element models. METHODS: Customized pre- and post-treatment computational fluid dynamics models of the patient's upper airway were built for comparison based on three-dimensional computed tomogram. The inhalation process was simulated using a constant volume flow rate for both models, and the wall was set to be rigid and stationary. Laminar and turbulent analyses were applied. RESULTS: Comparisons between before and after RME airway volume measurements showed that increases were only detected in nasal cavity volume, nasopharynx volume, and the most constricted area of the airway. Pressure, velocity, and turbulent kinetic energy decreased after dental expansion for laminar and turbulent flow. Turbulent flow shows relatively larger velocity and pressure than laminar flow. CONCLUSIONS: RME showed positive effects that may help understand the key reasons behind relieving the symptom of breathing disorders in this patient. Turbulence occurs at both nasal and oropharynx areas, and it showed relatively larger pressure and velocity compared to laminar flow.Item Finite Element Analysis as an Iterative Design Tool for Students in an Introductory Biomechanics Course(ASME, 2021-12) Higbee, Steven; Miller, Sharon; Biomedical Engineering, School of Engineering and TechnologyInsufficient engineering analysis is a common weakness of student capstone design projects. Efforts made earlier in a curriculum to introduce analysis techniques should improve student confidence in applying these important skills toward design. To address student shortcomings in design, we implemented a new design project assignment for second-year undergraduate biomedical engineering students. The project involves the iterative design of a fracture fixation plate and is part of a broader effort to integrate relevant hands-on projects throughout our curriculum. Students are tasked with (1) using computer-aided design (CAD) software to make design changes to a fixation plate, (2) creating and executing finite element models to assess performance after each change, (3) iterating through three design changes, and (4) performing mechanical testing of the final device to verify model results. Quantitative and qualitative methods were used to assess student knowledge, confidence, and achievement in design. Students exhibited design knowledge gains and cognizance of prior coursework knowledge integration into their designs. Further, student's self-reported confidence gains in approaching design, working with hardware and software, and communicating results. Finally, student self-assessments exceeded instructor assessment of student design reports, indicating that students have significant room for growth as they progress through the curriculum. Beyond the gains observed in design knowledge, confidence, and achievement, the fracture fixation project described here builds student experience with CAD, finite element analysis, three-dimensional printing, mechanical testing, and design communication. These skills contribute to the growing toolbox that students ultimately bring to capstone design.Item Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading(Medip Academy, 2018) Jiang, Feifei; Liu, Shengzhi; Chen, Andy; Li, Bai-Yan; Robling, Alexander G.; Chen, Jie; Yokota, Hiroki; Mechanical and Energy Engineering, School of Engineering and TechnologyBreast cancer-associated bone metastasis induces bone loss, followed by an increased risk of bone fracture. To develop a strategy for preventing tumor growth and protecting bone, an understanding of the mechanical properties of bone under tumor burden is indispensable. Using a mouse model of mammary tumor, we conducted finite element analysis (FEA) of two bone samples from the distal femur. One sample was from a placebo-treated mouse, and the other was from a mouse treated with the investigational drug candidate, PD407824, an inhibitor of checkpoint kinases. Mechanical testing and microCT images revealed that bone strength is improved by administration of PD407824. In response to loading to the knee, FEA predicted that the peaks of von Mises stress, an indicator of fracture yielding, as well as the third principal compressive stress, were higher in the placebo-treated femur than the drug-treated femur. Higher peak stresses in trabecular segments were observed in the lateral condyle, a critical region for integrity of the knee joint. Collectively, this FE study supports the notion that mechanical weakening of the femur was observed in the tumor-invaded trabecular bone, and chemical agents such as PD407824 may potentially assist in preventing bone loss and bone fracture.Item Mechanobiological wound model for improved design and evaluation of collagen dermal replacement scaffolds(Elsevier, 2021) Sohutskay, David O.; Buganza Tepole, Adrian; Voytik-Harbin, Sherry L.; Medicine, School of MedicineSkin wounds are among the most common and costly medical problems experienced. Despite the myriad of treatment options, such wounds continue to lead to displeasing cosmetic outcomes and also carry a high burden of loss-of-function, scarring, contraction, or nonhealing. As a result, the need exists for new therapeutic options that rapidly and reliably restore skin cosmesis and function. Here we present a new mechanobiological computational model to further the design and evaluation of next-generation regenerative dermal scaffolds fabricated from polymerizable collagen. A Bayesian framework, along with microstructure and mechanical property data from engineered dermal scaffolds and autograft skin, were used to calibrate constitutive models for collagen density, fiber alignment and dispersion, and stiffness. A chemo-bio-mechanical finite element model including collagen, cells, and representative cytokine signaling was adapted to simulate no-fill, dermal scaffold, and autograft skin outcomes observed in a preclinical animal model of full-thickness skin wounds, with a focus on permanent contraction, collagen realignment, and cellularization. Finite element model simulations demonstrated wound cellularization and contraction behavior that was similar to that observed experimentally. A sensitivity analysis suggested collagen fiber stiffness and density are important scaffold design features for predictably controlling wound contraction. Finally, prospective simulations indicated that scaffolds with increased fiber dispersion (isotropy) exhibited reduced and more uniform wound contraction while supporting cell infiltration. By capturing the link between multi-scale scaffold biomechanics and cell-scaffold mechanochemical interactions, simulated healing outcomes aligned well with preclinical animal model data. STATEMENT OF SIGNIFICANCE: Skin wounds continue to be a significant burden to patients, physicians, and the healthcare system. Advancing the mechanistic understanding of the wound healing process, including multi-scale mechanobiological interactions amongst cells, the collagen scaffolding, and signaling molecules, will aide in the design of new skin restoration therapies. This work represents the first step towards integrating mechanobiology-based computational tools with in vitro and in vivo preclinical testing data for improving the design and evaluation of custom-fabricated collagen scaffolds for dermal replacement. Such an approach has potential to expedite development of new and more effective skin restoration therapies as well as improve patient-centered wound treatment.Item Physical activity induced adaptation can increase proximal femur strength under loading from a fall onto the greater trochanter(Elsevier, 2021) Fuchs, Robyn K.; Carballido-Gamio, Julio; Keyak, Joyce H.; Kersh, Mariana E.; Warden, Stuart J.; Physical Therapy, School of Health and Human SciencesPhysical activity enhances proximal femur bone mass, but it remains unclear whether the benefits translate into an enhanced ability to resist fracture related loading. We recently used baseball pitchers as a within-subject controlled model to demonstrate physical activity induced proximal femur adaptation in regions associated with weight bearing and increased strength under single-leg stance loading. However, there was no measurable benefit to resisting common injurious loading (e.g. a fall onto the greater trochanter). A lack of power and a small physical activity effect size may have contributed to the latter null finding. Softball pitchers represent an alternative within-subject controlled model to explore adaptation of the proximal femur to physical activity, exhibiting greater dominant-to-nondominant (D-to-ND) leg differences than baseball pitchers. The current study used quantitative computed tomography, statistical parametric mapping, and subject-specific finite element (FE) modeling to explore adaptation of the proximal femur to physical activity in female softball pitchers (n = 25). Female cross-country runners (n = 15) were included as symmetrically loaded controls, showing very limited D-to-ND leg differences. Softball pitchers had D-to-ND leg differences in proximal femur, femoral neck, and trochanteric volumetric bone mineral density and content, and femoral neck volume. Voxel-based morphometry analyses and cortical bone mapping showed D-to-ND leg differences within a large region connecting the superior femoral head, inferior femoral neck and medial intertrochanteric region, and within the greater trochanter. FE modeling revealed pitchers had 19.4% (95%CI, 15.0 to 23.9%) and 4.9% (95%CI, 1.7 to 8.2%) D-to-ND leg differences in predicted ultimate strength under single-leg stance loading and a fall onto the greater trochanter, respectively. These data affirm the spatial and strength adaptation of the proximal femur to weight bearing directed loading and demonstrate that the changes can also have benefits, albeit smaller, on resisting loads associated with a sideways fall onto the greater trochanter.Item Resonance in the mouse tibia as a predictor of frequencies and locations of loading-induced bone formation(Springer, 2014-01) Zhao, Liming; Dodge, Todd; Nemani, Arun; Yokota, Hiroki; Biomedical Engineering, School of Engineering and TechnologyTo enhance new bone formation for the treating of patients with osteopenia and osteoporosis, various mechanical loading regimens have been developed. Although a wide spectrum of loading frequencies is proposed in those regimens, a potential linkage between loading frequencies and locations of loading-induced bone formation is not well understood. In this study, we addressed a question: Does mechanical resonance play a role in frequency-dependent bone formation? If so, can the locations of enhanced bone formation be predicted through the modes of vibration? Our hypothesis is that mechanical loads applied at a frequency near the resonant frequencies enhance bone formation, specifically in areas that experience high principal strains. To test the hypothesis, we conducted axial tibia loading using low, medium, or high frequency to the mouse tibia, as well as finite element analysis. The experimental data demonstrated dependence of the maximum bone formation on location and frequency of loading. Samples loaded with the low-frequency waveform exhibited peak enhancement of bone formation in the proximal tibia, while the high-frequency waveform offered the greatest enhancement in the midshaft and distal sections. Furthermore, the observed dependence on loading frequencies was correlated to the principal strains in the first five resonance modes at 8.0-42.9 Hz. Collectively, the results suggest that resonance is a contributor to the frequencies and locations of maximum bone formation. Further investigation of the observed effects of resonance may lead to the prescribing of personalized mechanical loading treatments.Item Simulation of mechanical environment in active lead fixation: effect of fixation helix size(The American Society of Mechanical Engineers, 2011-06) Zhao, Xuefeng; Wenk, Jonathan F.; Burger, Mike; Liu, Yi; Das, Mithilesh K.; Combs, William; Ge, Liang; Guccione, Julius M.; Kassab, Ghassan S.; Biomedical Engineering, School of Engineering and TechnologyThe risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance.Item Surrogate-based global optimization of composite material parts under dynamic loading(2017-08) Valladares Guerra, Homero Santiago; Tovar, Andres; Jones, Alan; Anwar, SohelThe design optimization of laminated composite structures is of relevance in automobile, naval, aerospace, construction and energy industry. While several optimization methods have been applied in the design of laminated composites, the majority of those methods are only applicable to linear or simplified nonlinear models that are unable to capture multi-body contact. Furthermore, approaches that consider composite failure still remain scarce. This work presents an optimization approach based on design and analysis of computer experiments (DACE) in which smart sampling and continuous metamodel enhancement drive the design process towards a global optimum. Kriging metamodel is used in the optimization algorithm. This metamodel enables the definition of an expected improvement function that is maximized at each iteration in order to locate new designs to update the metamodel and find optimal designs. This work uses explicit finite element analysis to study the crash behavior of composite parts that is available in the commercial code LS-DYNA. The optimization algorithm is implemented in MATLAB. Single and multi-objective optimization problems are solved in this work. The design variables considered in the optimization include the orientation of the plies as well as the size of zones that control the collapse of the composite parts. For the ease of manufacturing, the fiber orientation is defined as a discrete variable. Objective functions such as penetration, maximum displacement and maximum acceleration are defined in the optimization problems. Constraints are included in the optimization problem to guarantee the feasibility of the solutions provided by the optimization algorithm. The results of this study show that despite the brittle behavior of composite parts, they can be optimized to resist and absorb impact. In the case of single objective problems, the algorithm is able to find the global solution. When working with multi-objective problems, an enhanced Pareto is provided by the algorithm.