T cells are key agents in the adaptive immune response, responsible for robust and selective protection of the body against foreign pathogens. T cells are activated through their interaction with antigen-presenting cells (APCs) via a dynamic cell-cell interface called the immune synapse (IS). Numerous studies in recent years have shown that T cell activation is a mechanoresponsive process. Modulation of substrate rigidity and topology are emerging as powerful tools for controlling T cell activation. However, the majority of systems used to investigate the IS have used substrates that lack the rigidities and topographical complexities inherent in the physiological T cell - APC interface. Circumventing these limitations, elastomer micropillar arrays can be fabricated with physiologically-relevant rigidities and provide a topographically-deformable activating substrate. In this thesis, we examine the mechanisms behind T cell mechanosensing in order to gain a more complete understanding of T cell activation. More specifically, we take advantage of micropillar substrate properties to examine the IS in both 2D and 3D, seeking new insights into how the structural and mechanical features of the IS modulate T cell activity. We first investigate the traditional paradigm of T cell force generation at the 2D IS by seeking to characterize the temporal relationship between TCR signaling and force generation. We find that in both mouse naive and preactivated CD4+ T cells, TCR signaling is robust, dynamic, and localized to the pillar features. However, no temporal correlation is found between signaling and force generation. A potential reason for this lack of correlation is recent research showing that the physiological IS is a 3D interface that is topographically dynamic. This phenomenon complicates our interpretation of the 2D IS, as our micropillar system is protrusion-inducing substrate. In order to investigate the implications of topographical cues, we then characterize T cell activation in the 3D IS with respect to force generation and cytoskeletal development over time. We demonstrate that preactivated CD4+ T cells exhibit a dynamic and robust penetration into micropillar arrays. In the 3D IS, actin polymerization is again not correlated with force generation, but we find that microtubules (MTs) have a critical role in 3D T cell mechanosensing. Namely, MT architecture is correlated with the spatial distribution of force generation in the 3D IS, the centralization of microtubule-organizing center (MTOC) to the 3D IS is a mechanosensitive process that is modulated by surface rigidity, and while MT polymerization is not necessary for force generation, it is critical for maintaining synaptic integrity over time. Together, this work reveals important aspects of the underlying dynamics of the T cell cytoskeleton in IS formation and maintenance. The conclusions will help advance the concept of mechanobiology in immunology, which may in turn be leveraged towards the development of biomaterials that enhance T cell manufacturing in adoptive cell therapy.

The synovium is a specialized connective tissue that encapsulates diarthrodial joints like the knee, maintaining a low-friction environment for the articulating surfaces within. This tissue plays a key role in homeostasis by regulating solute transport in and out of the joint, and secreting lubricating factors into the synovial fluid. The predominant cell type in the synovium is the fibroblast-like synoviocyte (FLS), which resides on the intimal surface of the tissue and produces lubricating molecules such as hyaluronan. Because these cells directly face the synovial fluid and apposing tissue surfaces within the joint, they are exposed to a dynamic environment of mechanical stimuli generated during daily activity. This dissertation addresses the global hypothesis that FLS are mechanosensitive to distinct modes of shear stress generated in the knee during articulation, and that modulation of this sensitivity by chemical and physical factors of the osteoarthritic (OA) environment contributes to disease progression. Previous work has demonstrated that fluid-induced shear stress, generated as synovial fluid redistributes within the capsule during articulation, is a relevant mechanical stimulus for FLS. Exposure of FLS to fluid shear has been shown to modulate downstream functions such as lubricant secretion and the release of degradative matrix-metalloproteinases as induced by the cytokine interleukin-1 (IL-1), the latter indicating a link between mechanotransduction and the inflammatory environment of OA. The first goal of this dissertation was to further elucidate FLS mechanotransduction by characterizing the upstream response of FLS to fluid shear and determine the influence of IL-1 thereupon. The work presented herein demonstrates for the first time a robust calcium signaling response of FLS to fluid shear, a key upstream event in the mechanotransduction of physical stimuli. Key aspects of this response were significantly altered by pre-exposure to IL-1, indicating a pathologic modulation of normal mechanosensing in the OA environment. This effect was observed across bovine and human models and was found to be potentiated by both increasing intercellular communication and modulation of cell primary cilia. In addition to chemical factors such as cytokines, the degradation of cartilage during OA produces a physical factor that perpetuates disease state in the form of cartilage wear particles (CWP). These particles are released into the synovial fluid and attach directly to the synovium. We have previously shown that CWP induce FLS monolayers to release pro-inflammatory mediators of OA. The second goal of this dissertation was to investigate the effect of CWP on both cell-level function and tissue-level properties. To this end we showed first that CWP modulate the calcium signaling response of FLS to fluid shear in a contact dependent manner, and that inhibition of intercellular communication is a potential mechanism of this effect. In areas of the articulating capsule where apposing tissues slide in direct contact with each other, contact-induced shear stress provides another relevant physical stimulus to FLS. In this case of direct interaction between surfaces, the tissue-level frictional properties may affect the magnitude of shear stress presented to the cells within the intimal layer and thus influence mechanotransduction. A novel bioreactor was developed to characterize the effect of sliding contact on downstream functions of FLS within explant tissues. An increase in metabolic activity with culture under these conditions suggests that contact shear is a relevant stimulus for FLS. While previous work has characterized synovium friction properties in sliding contact against glass, relatively little is known of synovium tribology in native tissue configurations, or the influence of pathologic conditions such as CWP attachment. This dissertation reports for the first time low friction properties for synovium against other tissues within the joint such as cartilage and demonstrates a significant deleterious effect of CWP on these properties. The research presented in this dissertation further elucidates the processes of normal synoviocyte mechanotransduction, and by demonstrating that key chemical and physical factors of the OA environment modulate both cell and tissue-level functional properties, sheds light on the mechanisms by which the synovium contributes to disease progression. This sets the foundation for future work into synovium mechanotransduction of distinct physical stimuli and the relationship with tissue-level mechanical properties, and points towards clinical interventions that seek to restore the normal mechanical environment of the joint.

No description available.

Peat et al (2001) identified that 25% of the UK population suffers from knee pain, with 50% of this group being affected by knee osteoarthritis. Of this 50% of the population it has been suggested that 27.4 out of every 1000 knees are deemed suitable for replacement (arthroplasty). This study aimed to investigate the biomechanical and patient reported changes following total knee arthroplasty. A sample of 14 patients were recruited from the Lancashire Teaching Hospitals NHS Foundation trust all of who were diagnosed with tricompartmental osteoarthritis of the knee (K-L grade 2-4) and scheduled for the Zimmer NexGen CR total knee arthroplasty. The patients attended 4 assessments; preoperatively (baseline), six weeks, three months and six months postoperatively. At all assessments the patients performed three tasks, which were steady state gait, gait initiation and quiet standing whilst their kinematics and kinetics were measured. At these assessments patients completed self-reported questionnaires. Only 10 completed all assessments and were therefore considered in the final analysis. The results indicated that during quiet standing the coronal plane knee angle shifted alignment from varus to valgus (pc0.05), there was an increase in the sagittal plane knee moments (p < 0.05), there was increased external rotation about the hip (pc0.05) and an increased flexion moment about the hip (pc0.05). In the gait initiation task the results indicated a shift in the coronal plane angle from varus to valgus (pc0.05) and an increase in the decouple vector between the centre of mass and the centre of pressure (pc0.05). Walking gait identified the greatest number of changes where the external rotation about the ankle increased (p < O.OS), the plantar and dorsiflexion moments about the ankle increased (pc0.05), the coronal plane angle about the knee shifted from varus to valgus (p.c0.05), the knee adduction moments decreased (pc0.05), the coronal plane range of motion about the hip decreased (pc0.05), the internal rotation moment about the knee decreased (pc0.05), the anterior and posterior ground reaction forces increased (pc0.05) and the walking velocity and step length both increased (pc0.05). The patient self-reported questionnaire identified subjective improvements in pain, a reduction of symptoms, improved ability to participate in activities of daily living, improved participation in sport and recreation and a general improvement in quality of life (pc0.05). In conclusion, when successful the Zimmer NexGen total knee arthroplasty appears to significantly improve joint pain and function up to six months following postoperatively. A plateau effect was identified between six weeks and three months postoperatively, which may be partially due to the removal of walking aids.

Orientador: Fellippo Ramos Verri / Banca: Aldiéris Alves Pesqueira / Banca: Pedro Yoshito Noritomi / Resumo: O objetivo desse estudo foi comparar os resultados de rigidez do ensaio mecânico de compressão axial com a rigidez da análise por elementos Finitos (FEA), gerar modelos biomecânicos que apresentem com precisão a geometria tridimensional do osso e realizar análise pelo Método dos Elementos Finitos propondo uma metodologia para a simulação computacional mecânica de estruturas ósseas de peças de fêmures e tíbias de coelhos cadáveres. Previamente ao ensaio mecânico de compressão, fez-se uma análise mecânica da estrutura óssea, reconstruindo 20 modelos a partir de tomografia computadorizada utilizando o software de processamento de imagem ScanIP. Em seguida, foi realizada a análise mecânica de rigidez da estrutura óssea simulada pelo método dos elementos finitos 3D no software Ansys. Após construção da malha de elementos finitos, ensaios mecânicos de compressão axial foram realizados nas amostras e seus resultados de rigidez foram então comparados com os resultados de rigidez do modelo biomecânico. Nessa comparação o menor desvio apresentado foi de 0,02% e o maior desvio foi de 8,68%. A diferença entre a média da rigidez extrínseca dos ensaios foi de 1,07%. A média dos resultados para a rigidez intrínseca dos modelos biomecânicos obtidas do pós processamento foi 25258,63 N⁄mm. Concluiu-se que o uso dessa metodologia nos permitiu uma validação experimental do método dos elementos finitos aplicados à biomecânica das amostras testadas. Além disso, foi possível predizer o comportament... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to compare the stiffness results of the axial compression mechanical test with the FEA stiffness, to generate biomechanical models that accurately present the three- dimensional bone geometry and to perform analysis by the Finite Element Method proposing a methodology for the mechanical computational simulation of bony structures using parts of femurs and tibiae from rabbits that were healthy. Prior to mechanical compression testing, it was made a mechanical analysis of the bone structure, rebuilding 20 models from computed tomography using image processing software ScanIP. Then, it was performed mechanical analysis of stiffness of the simulated bone structure by the 3D finite element method in Ansys software. After finite element mesh construction, axial compression tests were performed on the samples and their stiffness results were compared with the stiffness results of the biomechanical model. In this comparison, the lowest deviation was 0,02% and the highest deviation was 8,68%. The difference between the mean extrinsic stiffness of the tests was 1.07%. The average of the results for the intrinsic rigidity of the biomechanical models obtained from the post-processing was 25258,63 N⁄mm. It was concluded that the use of this methodology enabled experimental validation of finite element method applied to biomechanics. Moreover, it was possible to predict the behavior of the bone because the accuracy of the analysis is better the more the biomechani... (Complete abstract click electronic access below) / Mestre

Luk Tze Chung. / "August 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 79-105). / Available also through the Internet via Dissertations & theses @ Chinese University of Hong Kong. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / Luk Tze Chung.

The tapering distribution of segment masses in the human arm helps in the generation of high ball release speeds in overarm throwing. However, the masses of the individual arm segments might not be optimal; arm segment masses could be optimised in order to improve throwing performance. The aim of this project was to identify and understand the optimal upper arm mass that results in the highest ball release speed in overarm throwing. The first study was a theoretical study, using a simple two-segment model of the arm to determine the optimal combination of arm segment masses that maximises ball release speed. This simplified throw was chosen to identify the basic mechanism causing changes in ball release speed with a heavier upper arm mass. The study identified that there is an optimal upper arm mass, but this optimum depends on the forearm mass and the shoulder torque. Furthermore, the study showed that a heavier forearm mass produces a lower ball release speed. An experimental approach was used in the second study to analyse the effect of additional upper arm mass on ball release speed and throwing mechanics in an overarm throw similar to that used by baseball pitchers. However, group analysis of the ball release speed did not reveal an optimal upper arm mass, and most of the kinematic, kinetic, and temporal variables were not affected by additional upper arm mass. However, analysing the ball release speed of each participant individually revealed that most participants increased their ball release speed, although there was considerable variation in the optimal upper arm mass. As the optimal upper arm masses in this study did not agree with those predicted in the first theoretical study, a more realistic three-dimensional model is needed to simulate the effect of upper arm mass on ball release speed. The third study was a combination of a theoretical and experimental approach. A three-dimensional model of the throwing arm was used to predict the participant's optimal upper arm mass and to determine the kinematic and kinetic variables that determine the optimal upper arm mass in overarm throwing. Even though the simulations did not accurately predict an athlete's optimal upper arm mass, the results highlighted that throwing athletes can benefit from a heavier upper arm mass as long as their ability to produce a high internal shoulder rotation angular velocity is not restricted. In summary, the findings of this project highlight that some athletes can benefit from a heavier upper arm mass to maximise their ball release speed without increasing the risk of injuries. However, as the optimal upper arm varies between athletes it is important to analyse each athlete individually.

Orientador: Araildo Lima da Silva / Co-orientador: Luiz Alberto Batista / Banca: José Trani Brandão / Banca: Mauro Pedro Peres / Banca: Leandro Nogueira Salgado Filho / Banca: Daniel das Virgens Chagas / Resumo: No esporte Stand Up Paddle (SUP), o praticante posiciona-se em bipedestação sobre a prancha e utiliza o remo para deslocar-se no mar. Apesar do aumento do número de praticantes assim como da quantidade de competições desta modalidade esportiva no brasileiro, ainda não se sabe das características biomecânicas envolvidas na remada. Assim, este estudo objetivou caracterizar biomecanicamente a conduta motora remada básica de passeio do esporte SUP. Inicialmente foi realizado um ciclograma funcional da remada e interpretação cinesiológica por meio da ferramenta ADE®, mediante captura de imagem, no plano sagital, da remada de passeio. Em seguida, na análise videogramétrica 3D, as imagens foram capturadas a uma frequência de 30Hz, importadas para o computador e digitalizadas no software Skillspector. Na identificação do comportamento cinético da remada básica de passeio SUP, foram estimadas variáveis cinéticas e foram identificados os esforços gerados em cada mão durante a remada, através de extensômetros posicionados em cada pega do remo. Pode-se identificar que 65.8% do ciclo de remada correspondem ao período de propulsão, enquanto que os 34.2% restantes correspondem ao período de recuperação. Observou-se maior deslocamento angular do ombro e do cotovelo, em comparação as articulações da coluna, quadril, joelho e tornozelo. Em relação as características cinéticas, constatou-se que a Energia Cinética e a Quantidade de movimento aumentam durante a remada, assim como o Trabalho e o Impulso foram positivos. Deste modo, pode-se afirmar que a remada básica de passeio do SUP é uma conduta motora multiplanar e que as articulações do ombro e cotovelo são as responsáveis pelos movimentos da remada. Também pode-se observar que os maiores esforços gerados pelo executante são identificados na pega inferior / Abstract: In sport Stand Up Paddle (SUP), the practitioner stands in standing position on the board and use the paddle to move offshore. Despite the increasing number of practitioners as well as the amount of competitions of this sport throughout Brazil, it is not known biomechanical characteristics involved in rowing. This study aimed to characterize biomechanically paddling basic motor conduct SUP sport ride. In this study, 24 cycles of stroke were analyzed. Initially it performed a functional cyclegram of stroke and kinesiology interpretation by ADE® tool through image capture, in sagittal plane, rice paddle. Then in 3D videogrammetric analysis, the images were captured at a frequency of 30Hz, imported to the computer, edited by Virtualdub software and scanned in Skillspector software. In identifying the kinetic behavior of the basic stroke SUP ride kinetic variables were estimated, and the efforts were identified generated in each hand during the stroke, by strain gauges positioned on each handle. It can be identified that 65.8% of the stroke cycle corresponding to the period of propulsion, while the remaining 34.2% corresponding to the recovery period. A higher angular displacement of the shoulder and elbow compared the joints of the spine, hip, knee and ankle. Regarding the kinetic characteristics, it was found that the Kinetic Energy and Momentum increase during stroke, as well as the Work and Impulse were positive. Thus, it can be said that the basic paddling SUP tour is a motor behavior multiplane and the joints of the shoulder and elbow are responsible for rowing movements. It may also be noted that the greatest efforts generated by the performer are identified in the IP, mainly from the beginning to the end of the stroke / Doutor

Total hip arthroplasty (THA) is the treatment of choice to relieve joint pain and loss of mobility as a result of advanced stage osteoarthritis or other hip pathologies. Despite their general success, THAs do fail, with revision rates estimated near 5% per year. Instability, defined as the complete subluxation (dislocation) of the femoral head from the acetabular socket - which usually occurs due to implant impingement - has recently supplanted wear-induced osteolytic aseptic loosening as the leading cause of failure in THA. Soft tissue integrity has long been recognized as influencing joint stability, and therefore there has been great interest recently in improving soft tissue restoration following THA. However, there is little quantitative information related to the degree of soft tissue repair necessary to restore joint stability. Additionally, impingement events, besides their role in prelude to frank dislocation, hold potential to damage new-generation hard-on-hard bearings, due to the relatively unforgiving nature of the materials and designs. Despite the largely biomechanical nature of these impingement-related complications, they remain under-investigated relative to their burden of morbidity. In addition to impingement, failure modalities unique to hard-on-hard bearings merit careful biomechanical scrutiny. This includes investigation of catastrophic fracture in ceramic-on-ceramic bearings, as well as analysis of patient, implant and surgical variables associated with increased wear and adverse soft tissue engagement potential for metal-on-metal implants. Toward the goal of improving current biomechanical understanding of failure modalities in THA and to provide an objective basis for orthopaedic surgeons to choose the most favorable implants and to identify optimal intraoperative parameters which minimize failure propensity, a novel, anatomically-grounded finite element model was developed, and used to perform multiple parametric finite element investigations of these failure modes.

Introduction. L’objectif de cette étude est de déterminer la réponse mécanique du colon en traction uniaxiale jusqu’à la rupture et quels sont les facteurs la modifiant.Matériel et méthodes Nous avons réalisé des essais dynamiques uniaxiaux de spécimens coliques humains. Trois vitesses de sollicitation étaient testées : dynamique (1m/s), intermédiaire (10cm/s) et quasi-statique (1cm/s).Résultats Vingt-huit colons humains réfrigérés ont été testés avec un total de 344 spécimens. Le colon présente un comportement mécanique bicouche. Le comportement mécanique est variable en fonction de la localisation sur le cadre colique. Le sexe représente également un facteur responsable d’une modification de la réponse mécanique du colon. La durée de conservation des corps et le tænia coli ne représentaient pas un facteur influençant le comportement mécanique dynamique du colon.La réponse mécanique enregistrée est différente en fonction de l’orientation de la sollicitation : les niveaux de contrainte et de déformation étaient plus élevés sous sollicitation transversale.La vitesse de sollicitation modifie la réponse mécanique enregistrée avec des niveaux de rupture plus faibles sous sollicitation dynamique.Le type de conservation modifie la déformation et la force nécessaires pour obtenir des lésions coliques.ConclusionLe colon se comporte comme un matériau viscoélastique ductile et bicouche. Son comportement mécanique est dépendant de la localisation sur le cadre colique, du sexe, des méthodes de conservation et des vitesses de sollicitation. Cette étude permettra l’intégration de données biomécaniques dans des modèles de traumatologie virtuelle ou de simulation chirurgicale. / IntroductionThe objective of this study is to determine the mechanical response of the colon in uniaxial traction until rupture and what are the modifying factors.Material and methodsWe performed uniaxial dynamic tests of human colonic specimens. Three loading speeds were tested: dynamic (1m/s), intermediate (10cm/s) and static (1cm/s).ResultsTwenty-eight refrigerated human colons were tested with a total of 344 specimens. The colon exhibits a bi-layered mechanical behavior.The mechanical behavior is variable according to the localization on the colonic frame with a more elastic behavior of the right colon and the sigmoid colon. Gender is also a factor responsible for a change in the mechanical response of the colon. The shelf life of the body and tænia coli were not a factor influencing the mechanical behavior of the colon under dynamic solicitation.The recorded mechanical response is different depending on the orientation of the stress: the stress and strain levels were higher under circumferential stress.The loading speed changes the recorded mechanical response. The colon is more elastic in a quasi-static situation and has lower levels of rupture under dynamic stress. Under dynamic loading, the type of preservation does not modify the stiffness of the tissue but modifies the stress and strain necessary to obtain colonic lesions.ConclusionThe colon behaves like a ductile and bilayer viscoelastic material. Its mechanical behavior is dependent on the location on the colonic frame, gender, methods of conservation and rates of solicitation. This study will allow the integration of biomechanical data into models of virtual trauma or surgical simulation.