O domínio da locomoção é essencial para a execução adequada de diferentes atividades da vida diária. Atualmente, utiliza-se de vários instrumentos de treinamento para o retorno às atividades funcionais, como a esteira rolante e o elíptico. O problema desta pesquisa está baseado na pergunta: Qual é o padrão de ativação dos músculos do membro durante o exercício no elíptico? O objetivo principal é analisar e descrever as características biomecânicas da aceleração e da atividade eletromiográfica do andar em um elíptico. Participaram 42 adultos divididos em três grupos: grupo adulto jovem, constituído por 20 adultos jovens, grupo adulto idoso, constituído por 12 adultos idosos, ambos praticantes de atividade física regular e sem lesões ou problemas no aparelho locomotor, e grupo de adultos pós acidente vascular encefálico, constituído por 10 indivíduos. O questionário internacional de atividade física e os testes para a avaliação qualitativa da marcha, o teste de categoria de ambulação funcional e teste de equilíbrio em pé foram aplicados. Foram utilizados um acelerômetro tridimensional e um eletromiógrafo de superfície com 16 canais, além de uma esteira ergométrica e um elíptico. Após a familiarização com os equipamentos, os sujeitos andaram no elíptico e na esteira enquanto que a atividade miolétrica e a aceleração tibial foram coletadas. O tempo de coleta foi de 20s e a frequência de aquisição foi 2kHz. As curvas do envoltório linear foram geradas e normalizadas pela base do tempo. Resultados: A amplitude da ativação muscular foi maior durante a marcha na esteira, na fase de propulsão, no grupo de pessoas com AVE e idosos e nos músculos tibial anterior e bíceps femoral (p<0,0001). A menor ativação muscular foi observada no músculo reto abdominal, no grupo de adultos jovens, na fase pré-balanço (p<0,0001). Na análise qualitativa a aceleração da tíbia foi menor para o equipamento elíptico em comparação com a esteira. Os resultados favorecem a indicação do elíptico para o processo de recuperação da locomoção de pessoas com dificuldade para andar com limitações neurológicas ou ortopédicas / The achievement of the locomotion is essential for the adequate performance of different daily life activities. Several training instruments for the return to the functional activities exist, such as the treadmill and the elliptical. The research problem is: What is the lower limb muscle activation pattern during exercising in an elliptical trainer? The aim of this study is to analyze and describe the biomechanical characteristics of the acceleration and myoeletrical activity during walking in an elliptical trainer. The participants were 42 adults divided into three groups: young adult group (n=20), old adult group (n=12), both physically active and without any chronic pain or orthopedic conditions that could alter gait patterning, and chronic stroke adults (n=10). The international questionnaire of physical activity, the gait functional test and balance test were applied. We used one accelerometer and 16-channels electromyography system, a treadmill and an elliptical trainer. They walked on the elliptical and on the treadmill while the myoelectrical activity of 8 muscles and the tibial acceleration were recorded. The recording time was 20 s and sampling frequency was 2 kHz. The ensemble average was calculated for each variable. Results: The muscle activation was the highest at the treadmill, for propulsion phase, for the people with stroke and elderly and for the muscles Tibialis Anterior and Biceps Femoris (p<0.0001). The smallest muscle activity was observed on the Rectus Abdominus muscle, for the young adults, for pre contact phase (p<0.0001). The tibial acceleration was smaller for the elliptical than the treadmill. The results support the use of the elliptical for the rehabilitation of gait impairments related to neurological or orthopedic limitations

In the classic Hill model for muscle contraction, the split between the muscle and tendon is arbitrary and the problem lacks a unique solution. Instead of reformulating the problem to a differential-algebraic equation and solving for a set of initial conditions, a constant tendon length is commonly assumed in musculoskeletal simulation tools. This assumption has not been thoroughly tested and introduces errors of unknown magnitude to the simulations. In this thesis, the contractile element of the Hill model is modelled as a friction clutch in parallel to a viscous damper. This provides an evolution law for the muscle length by which the muscle speed is numerically calculated taking into account a non-zero tendon speed. A simple biceps curl is simulated with the friction clutch model and compared to corresponding commercial musculoskeletal simulations. Overall, the results are similar, in particular for the muscle lengths which are almost identical in every simulation (0.00-0.42% difference). The difference in tendon speed is 0.00-3.26%, with upwards tendencies. In general, the error percentage of the tendon speed appears to decrease by the same amount that the contraction speed is reduced. Conclusively, it can be said that the introduced friction clutch model delivers comparative outcomes to a commercial musculoskeletal simulation software, while not assuming a constant tendon length. However, while presenting a relatively simple solution, an increased computation time is to be expected due to the need of a differential equation solver. Further investigation regarding implementation and computing times in more complex simulations may provide an alternative approach to conventional musculoskeletal simulations.

Following a spinal cord injury (SCI), the paralyzed extremities undergo muscle atrophy and decrease in bone mineral density (BMD) due in part to the loss of physiological loading. It is crucial to prevent musculoskeletal deterioration so the population is less susceptible to fractures, and could take advantage of stem cell treatment if it becomes available. Functional electrical stimulation (FES) has been shown to advantageously train the paralyzed extremities. However, there is a risk of fracture during FES due to low BMD of individuals with SCI. Therefore, the forces generated during FES need to be modeled so researchers and clinicians safely administer this intervention. The purpose of this project was to develop a biomechanical or mathematical model to estimate the internal compressive and shear forces at the distal femur, a common fracture site for individuals with SCI during FES. Therefore, a two-dimensional static model was created of the lower extremity in the supine and seated positions. The compressive and shear forces at the distal femur were estimated for both positions during FES. These internal compressive and shear forces estimated at the distal femur by the supine model were compared to those estimated by the standing model. Also, for the seated model, the compressive and shear forces at the distal femur estimated by a tetanic muscle contraction were compared to those estimated by a doublet muscle contraction. Finally, the supine model was validated using experimental testing. The primary findings are 1) the standing model estimated more compressive force and less shear force at the distal femur compared to the supine model when position and quadriceps muscle force remain constant and 2) for the seated model, a tetanic quadriceps muscle contraction predicts greater compressive and shear at the distal femur compared to a doublet muscle contraction. Also the validation testing revealed a 3.4% error between the supine model and the experimental testing. These models provide valuable insights into the internal forces at the distal femur during FES for those with SCI.

<div><p>The cellular protein pool exists in a state of dynamic equilibrium, such that a balance between protein synthesis and degradation is maintained to sustain protein homeostasis. This equilibrium is essential for normal cellular functions and hence alteration in protein dynamics has several pathological implications in developing and adult tissues. Recent progress in mass spectrometry (MS) and metabolic labeling techniques has advanced our understanding of the mechanisms of protein regulation in cultured cells and less complicated multicellular organisms. However, methods for the analysis of the dynamics of intra- and extra-cellular proteins in embryonic and adult tissues remain lacking.</p><p>To address this gap, we developed a metabolic labeling technique that enables labeling the nascent murine proteome via injection of non-canonical amino acids (ncAAs), which can be selectively enriched by “clickable” tags for identification and quantification. Using this technique, we developed a MS-based method for the selective identification and quantification of the intra- and extra-cellular newly synthesized proteins in developing murine tissues. We then applied this technique to study the dynamic regulation of extracellular matrix (ECM) proteins during embryonic and adolescent musculoskeletal development. We show that the applied technique enables resolving differences in the nascent proteome of different developmental time points with high temporal resolution. The technique can also reveal protein dynamic information that cannot be captured by the traditional proteomic techniques. Additionally, we identified key ECM components that play roles in musculoskeletal development to provide insights into the mechanisms of musculoskeletal tissue regeneration.</p><p>To fully characterize our labeling technique, we developed a mathematical model to describe the biodistribution kinetics of azidohomoalanine (Aha), the most widely used ncAA, in murine tissues. The model enabled measuring the relative rates of protein synthesis and turnover in different tissues and predicting the effect of different dosing regimens of Aha on the degree of protein labeling. Finally, we analyzed the plasma metabolome of Aha-injected mice to investigate the impact of Aha incorporation on normal physiology. The analysis revealed that Aha administration into mice does not significantly perturb metabolic functions. Taken together, the findings presented in this dissertation demonstrate the utility of the ncAA labeling technique in mapping protein dynamics in mammalian tissues. This will ultimately have a significant impact on our understanding of protein regulation in health and disease. </p></div><br>

Osteoarthritis (OA) is a debilitating disease affecting roughly 31 million Americans. The incidence of OA is significantly higher for persons who have suffered a transtibial amputation. Abnormal cartilage stress can cause higher OA risk, however it is unknown if there is a connection between exercise type and cartilage stress. To help answer this, a tibiofemoral FEA model was created. Utilizing linear elastic isotropic materials and non-linear springs, the model was validated to experimental cadaveric data. In a previous study, 6 control and 6 amputee subjects underwent gait and cycling experiments. The resultant knee loads were analyzed to find the maximum compressive load and the respective shear forces and rotation moments for each trial, which were then applied to the model. Maximum tibial contact stress values were extracted for both the medial and lateral compartments. Only exercise choice in the lateral compartment was found to be a significant interaction (p<0.0001). No other interactions in either compartment were significant. This suggests that cycling reduces the risk for lateral OA regardless of amputation status and medial OA risk is unaffected. This study also developed a process for creating subject-specific FEA models.

This project concerns the computational solution of inverse problems formulated as partial differential equation (PDE)-constrained optimization problems with interior data. The areas addressed are twofold. First, we present a novel software architecture designed to solve inverse problems constrained by an elliptic system of PDEs. These generally require the solution of forward and adjoint problems, evaluation of the objective function, and computation of its gradient, all of which are approximated numerically using finite elements. The creation of specialized "layered"' elements to perform these tasks leads to a modular software structure that improves code maintainability and promotes functional interoperability between different software components. Second, we address issues related to forward model definition in the presence of boundary condition (BC) uncertainty. We propose two variational formulations to accommodate that uncertainty: (a) a Bayesian formulation that assumes Gaussian measurement noise and a minimum strain energy prior, and (b) a Lagrangian formulation that is completely free of displacement and traction BCs. This work is motivated by applications in the field of biomechanical imaging, where the mechanical properties within soft tissues are inferred from observations of tissue motion. In this context, the constraint PDE is well accepted, but considerable uncertainty exists in the BCs. The approaches developed here are demonstrated on a variety of applications, including simulated and experimental data. We present modulus reconstructions of individual cells, tissue-mimicking phantoms, and breast tumors.

A polyconvex continuum-level proteoglycan Cauchy stress function was developed based on the continuum electromechanical Poisson-Boltzmann unit cell model for proteoglycan interactions. The resulting proteoglycan model was combined with a novel collagen fibril model and a ground substance matrix material to create a polyconvex constitutive finite element model of articular cartilage. The true collagen fibril modulus , and the ground substance matrix shear modulus , were varied to obtain the best fit to experimental tension, confined compression, and unconfined compression data for native explants and explants cultured in insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Results indicate that culture in IGF-1 results in a weakening of the COL fibers compared to native explants, and culture in TGF-β1 results in a strengthening of the COL fibers compared to native explants. These results elucidate the biomechanical changes in collagen fibril modulus, and ground matrix shear modulus following in vitro culture with IGF-1 and TGF-β1. Understanding the constitutive effects of growth factor stimulated culture may have applications in AC repair and tissue engineering.

A poroelastic finite element model of a heterogeneous articular cartilage disc was created to examine the tissue response to low amplitude (± 2% strain), low frequency (0.1 Hz) dynamic unconfined compression (UCC). A strong correlation has been made between the relative fluid velocity and stimulation of glycosaminoglycan synthesis. A contour plot of the model shows the relative fluid velocity during compression exceeds a trigger value of 0.25 μm/s at the radial periphery. Dynamic UCC biochemical results have also reported a higher glycosaminoglycan content in this region versus that of day 0 specimens. Fluid velocity was also found not to be the dominant physical mechanism that stimulates collagen synthesis; the heterogeneity of the fluid velocity contour plot conflicts with the homogeneous collagen content from the biochemical results. It was also found that a Tresca (shear) stress trigger of 0.07 MPa could provide minor stimulation of glycosaminoglycan synthesis. A feasibility study on modeling a heterogeneous disc was conducted and found convergence issues with the jump in properties from the superficial to middle layers of the disc. It is believed that the superficial layer contains material properties that allow the tissue to absorb much of the compressive strain, which in turn increases pressure and causes convergence issues in ABAQUS. The findings in this thesis may help guide the development of a growth and remodeling routine for articular cartilage.

Transtibial amputees are at increased risk of contralateral hip and knee joint osteoarthritis, likely due to abnormal biomechanics. Biomechanical challenges exist for transtibial amputees in gait and cycling; particularly, asymmetry in ground/pedal reaction forces and joint kinetics is well documented and state-of-the-art passive and powered prostheses do not fully restore natural biomechanics. Elliptical training has not been studied as a potential exercise for rehabilitation, nor have any studies been published that compare joint kinematics and kinetics and ground/pedal reaction forces for the same group of transtibial amputees in gait, cycling, and elliptical training. The hypothesis was that hip and knee joint kinematics and kinetics and ground and pedal reaction forces would differ due to exercise (gait, cycling, elliptical) amputee status (amputated, control [non-amputated]), and leg (dominant [intact], non-dominant [amputated]). Ten unilateral transtibial amputees and ten control participants performed the three exercises while kinematic and kinetic data were collected. Hip and knee joint flexion angle, resultant forces, and resultant moments were calculated by inverse dynamics for the dominant and non-dominant legs of both participant groups. Joint biomechanics and measured ground/pedal reaction forces were then compared between exercises, between the dominant and non-dominant legs within each participant group, and across participant groups. Significant differences in hip and knee joint flexion angles and timing, compressive forces, extension-flexion (EF) and adduction-abduction (AddAbd) moments, and anterior-posterior (AP) and lateral-medial (LM) reaction forces were found. Particularly, transtibial amputees showed maximum knee flexion angle asymmetry as compared to controls in all three exercises. Maximum hip and knee compressive forces, EF moments, and AddAbd moments were lowest in cycling and highest in gait. Asymmetry in amputee midstance knee flexion and timing in v gait, coupled with low maximum EF moment for the non-dominant leg, suggests that amputees avoid contraction of the non-dominant quadriceps muscle. Knee flexion angle and EF moment asymmetry in elliptical training suggests that a similar phenomenon occurs. Asymmetry in AP and LM reaction forces in gait, but not other exercises, suggests that exercises that constrain kinematics reduce loading imbalances. The results suggest that cycling and elliptical training should be recommended to transtibial amputees for rehabilitation due to reduced hip and knee joint forces and moments. Elliptical training may be preferred over gait due to decreased joint loading and loading asymmetry, but some asymmetry and differences from control participants still exist. Non-weight bearing exercises such as cycling may be best at reducing overall joint loading and joint load asymmetry but do not eliminate all kinematic and temporal asymmetries. Current state-of-the-art prosthetic leg design is insufficient in restoring natural biomechanics not only in gait but also in cycling and elliptical training. Improved prosthesis kinematics that restore non-dominant knee flexion in amputees to normal levels could help reprogram quadriceps muscle patterns in gait and elliptical training and hip and knee joint biomechanical asymmetries. Further work in comparing contralateral and prosthesis ankle joint biomechanics would help to elucidate the relationship between prosthesis design and its impact on lower limb joint biomechanics.

Here we describe a finite element model of the mechanical stresses and strains involved in the growth and development of epithelial cancers, specifically pancreatic ductal adenocarcinoma (PDAC). We model a growing tumor swelling over time, modeled as fluid influx in response to changing solute concentrations. Stresses and strains are computed in surrounding material regions in response to this swelling. Further studies are conducted into the relative impacts of factors such as basement membrane thickness, stiffness, and duct radius. We observe that normal stresses are confined mostly to the basement membrane layer and hypothesize that there exists some threshold for axial stress beyond which the basement membrane ruptures and cancer is able to invade into the surrounding tissue.