Tendon and ligament injuries are common orthopedic problems that have an enormous impact on the quality of life of affected patients. Despite the frequency at which these injuries occur, current treatments are unable to restore native function to the damaged tissue. Because of this, reinjury is common. It is well known that mechanical stimulation is beneficial for promoting tendon and ligament development and tissue homeostasis; however, the specific mechanisms remain unclear. The transcription factor scleraxis (Scx) is an interesting candidate for mediating the tendon and ligament mechanoresponse, as it has been shown that Scx expression is induced by cyclic mechanical strain in tenocytes and is required for mechanically-induced stem cell tenogenesis. Moreover, Scx expression is increased in adult tendons following exercise. The studies described in this dissertation therefore focus on the combined role of Scx and mechanical stimulation in two contexts: 1) influencing ligament cell differentiation and 2) regulating adult tenocyte behavior. In the first study, transient Scx overexpression combined with mechanical strain in a 3D collagen hydrogel model was investigated as a means of deriving mature ligament cells from stem cells for use in ligament tissue engineering. Scx overexpression in C3H10T1/2 cells cultured in collagen hydrogels under static strain resulted in increased construct contraction and cell elongation, but no concurrent increase in the expression of ligament-related genes or production of glycosaminoglycans (GAG). When combined with low levels of cyclic strain, Scx overexpression resulted in increased mechanical properties of the tissue constructs, increased GAG production, and increased expression of ligament-related genes compared to cyclic strain alone. Together, these results demonstrate that Scx overexpression combined with cyclic strain can induce ligament cell differentiation and suggest that Scx does so by improving the mechanosensitivity of cells to cyclic strain. In the second study, the role of Scx in adult tenocyte mechanotransduction was explored using RNA-sequencing (RNA-seq) and small interfering RNA (siRNA) technologies. Equine tenocytes were exposed to siRNA targeting Scx or a control siRNA and maintained under cyclic mechanical strain prior to being submitted for RNA-seq. Comparison of the resulting transcriptomes revealed that Scx knockdown decreased the expression of several genes encoding important focal adhesion adaptor proteins. Correspondingly, Scx-depleted tenocytes showed abnormally long focal adhesions, decreased cytoskeletal stiffness, and an impaired ability to migrate on soft surfaces. This suggests that Scx regulates the tenocyte mechanoresponse by promoting the expression of focal adhesion-related genes. Combined, the results of these studies support a role for Scx in tendon and ligament cell mechanotransduction and identify the regulation of genes related to maintaining the cell-extracellular matrix connection and cytoskeletal dynamics as a potential mechanism. These findings enhance our understanding of how mechanical stimulation influences cell behavior and provide new research directions and methodologies for future studies of tendon and ligament mechanobiology. / Ph. D.

Yes / Objective To identify the injury history features reported by patients with ACL injuries and determine whether history may be used to identify patients requiring follow-up appointments from acute trauma services. Multi-site cross-sectional service evaluation using a survey questionnaire design conducted in the UK. The four injury history features investigated (LIMP) were ‘Leg giving way at the time of injury’, ‘Inability to continue activity immediately following injury’, ‘Marked effusion’ and ‘Pop (heard or felt) at the time of injury’. 194 patients with ACL injury were identified of which 165 (85.5%) attended an acute trauma service. Data on delay was available for 163 (98.8%) of these patients of which 120 (73.6%) had a follow-up appointment arranged. Patients who had a follow-up appointment arranged waited significantly less time for a correct diagnosis (geometric mean 29 vs 198 days; p<0.001) and to see a specialist consultant (geometric mean 61 vs 328 days; p<0.001). Using a referral threshold of any 2 of the 4 LIMP injury history features investigated, 95.8% of patients would have had a follow-up appointment arranged. Findings support the value of questioning patients on specific injury history features in identifying patients who may have suffered ACL injury. Using a threshold of 2 or more of the 4 LIMP history features investigated would have reduced the percentage of patients inappropriately discharged by 22.2%. Evidence presented suggests that this would significantly reduce the time to diagnosis and specialist consultation minimising the chance of secondary complications.

A ruptura total ou parcial do ligamento cruzado cranial (LCCr), é considerada uma das principais causas de instabilidade no cão e está entre as mais freqüentes afecções ortopédicas no cão. A ruptura do ligamento cruzado cranial (RLCCr) implica em tratamento cirúrgico por artroscopia ou artrotomia e se faz necessária a retirada dos seus resquícios e a sua substituição. Trinta e oito amostras de LCCr rompidos de animais submetidos ao tratamento cirúrgico para RLCCr e 13 amostras de LCCr íntegro de cadáveres de cães que tenham vindo a óbito por diferentes causas e sem histórico de doença articular foram coletadas para a realização de um estudo morfométrico, ultra-estrutural e imuno-histoquímico das células e componentes da matriz extracelular presentes no LCCr desses cães. Os cortes histológicos foram corados pela Hematoxilina-Eosina para análise histopatológica, Picrossirius-Hematoxilina para análise do colágeno, Resorcina- Fucsina para estudo das fibras do sistema elástico e Alcian-Blue-PAS para proteoglicanas. Os resultados sugeriram que houve diferença significativa entre os LCCr rompidos do grupo dos Labradores e as amostras íntegras do grupo controle no que diz respeito às alterações celulares. Em relação ao estudo de fibras colágenas a área ocupada foi significativamente maior no grupo controle. Não houve diferença significativa entre os grupos em relação às fibras do sistema elástico, entretanto, houve correlação entre a densidade linear destas fibras com a idade dos animais. Também foi possível estabelecer uma correlação entre peso e idade e, entre peso e tempo de evolução da doença articular. No estudo imuno-histoquímico para &alpha;-actina de músculo liso e Caspase 3, o grupo cirúrgico apresentou maior número de marcações positivas que o grupo controle. / Total or partial rupture of the cranial cruciate ligament (CCL) is one of the main causes of instability on dogs and is one of the most frequent orthopedic conditions of the dog. The rupture of CCL demands surgical procedure by arthroscopy or arthrotomy and the extraction and replacement of its remaining fragments is needed. Thirty-eight samples of ruptured CCL, collected during the surgical time and thirteen samples of intact CCL collected from cadavers of dogs without articular disease history were examined in this study. Morphometric, ultrastructural and immunohystochemical techniques were realized to study cells and extracellular matrix of CCL samples. The tissue sections were stained by Hematoxilyn-Eosin to histopathological study, Picrosirius-Hematoxilyn to collagen study, Resorcin-Fucsin to elastic fibers study and Alcian Blue-PAS to proteoglicans study. The results suggest that there were signifcant differences between the ligaments of the Labrador retrievers and the intact ligaments of the control group regarding the cellular changes. The control group had a significant larger area occupied by collagen fibers than the other groups. There is no statistical difference on elastic fibers among the groups. However the linear density of elastic system fibers could be correlationated with age of dogs. There was a correlation between weight and age, and betwwen weight and time of development of articular disease. Immunohistochemical study showed more positive cells to &alpha;-smooth muscle actin and caspase-3 in the ruptured CCL than the control group.

Li Chi Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong,1995. / Includes bibliogrpahical references (leaves 54-68). / Abstract --- p.1 / Acknowledgments --- p.4 / Lists of Figures --- p.5 / List of Tables --- p.8 / Chapter Chapter 1 --- Introduction --- p.9 / Chapter 1.1 --- Ligamental Injury --- p.9 / Chapter 1.2 --- ACL Injury --- p.10 / Chapter 1.3 --- Patellar Tendon and Anterior Cruciate Ligament --- p.11 / Chapter 1.4 --- Patellar Tendon Bone Graft --- p.13 / Chapter 1.41 --- Strength of the Patellar Tendon Bone Graft --- p.13 / Chapter 1.42 --- Use of the Patellar Tendon Bone Graft --- p.14 / Chapter 1.5 --- Patellar Tendon Bone Graft in Anterior Cruciate Ligament Reconstruction --- p.14 / Chapter 1.6 --- Complications of Anterior Cruciate Ligament Reconstruction after the Use of Patellar Tendon Bone Graft --- p.16 / Chapter 1.7 --- Healing of the Patellar Tendon Donor Site --- p.17 / Chapter 1.8 --- Objective of the Study --- p.22 / Chapter 1.9 --- Significance of the Study --- p.22 / Chapter Chapter 2 --- Material & Method --- p.24 / Chapter 2.1 --- Animal Model --- p.24 / Chapter 2.2 --- Grouping --- p.24 / Chapter 2.3 --- Operative Procedure --- p.24 / Chapter 2.4 --- Method of Assessment --- p.26 / Chapter 2.41 --- Gross Morphology --- p.26 / Chapter 2.42 --- Biomechanical Testing --- p.27 / Chapter 2.43 --- Biochemical Assay --- p.28 / Chapter 2.43.1 --- Water Content --- p.29 / Chapter 2.43.2 --- Collagen Content --- p.29 / Chapter 2.44 --- Histology --- p.30 / Chapter 2.45 --- Immunohistochemistry --- p.31 / Chapter 2.5 --- Statistics --- p.32 / Chapter Chapter 3 --- Results --- p.33 / Chapter 3.1 --- Operation Complications --- p.33 / Chapter 3.2 --- Gross Morphology --- p.33 / Chapter 3.21 --- Dimension of the Patellar Tendon --- p.33 / Chapter 3.22 --- Dimension of the Patellar Tendon Bone Graft --- p.33 / Chapter 3.23 --- Dimension of the Remain Patellar Tendon --- p.34 / Chapter 3.24 --- Gross Appearance of the Patellar Tendon Donor Site --- p.35 / Chapter 3.3 --- Biomechanical Testing --- p.36 / Chapter 3.31 --- Failure Load --- p.36 / Chapter 3.32 --- Ultimate Stress --- p.37 / Chapter 3.33 --- Stiffness --- p.37 / Chapter 3.34 --- Energy Absorbed before Failure --- p.38 / Chapter 3.4 --- Biochemical Assay --- p.38 / Chapter 3.41 --- Water Content --- p.38 / Chapter 3.42 --- Collagen Content --- p.39 / Chapter 3 .5 --- Histology & Immunohistochemistry --- p.39 / Chapter 3.51 --- Morphology of Control Tendon --- p.40 / Chapter 3.52 --- Morphology of Experimental Tendon with 'Open' Procedure --- p.40 / Chapter 3.53 --- Morphology of Experimental Tendon with 'Close' Procedure --- p.41 / Chapter 3.54 --- Healing at the Patellar and Tibial Insertion Site --- p.41 / Chapter 3.55 --- Morphology of the Cartilage Surface --- p.42 / Chapter Chapter 4 --- Discussion & Conclusion --- p.43 / Chapter 4.1 --- Gross Morphology --- p.43 / Chapter 4.2 --- Biomechanical Testing --- p.45 / Chapter 4.3 --- Biochemical Assay --- p.47 / Chapter 4.4 --- Histology & Immunohistochemistry --- p.49 / Chapter 4.5 --- Conclusion --- p.51 / References --- p.54 / Figures / Tables / Appendix

Les traumatismes au genou, tels que les ruptures du ligament croisé antérieur, sont particulièrement fréquentes lors de la pratique d’un sport ou d’une activité physique. La conséquence à moyen ou long terme est l’apparition d’une arthrose précoce. Si l’activité physique peut être indirectement la cause du développement de cette pathologie, elle constitue également une forme de thérapie non pharmacologique. Les effets de l’exercice seront étudiés aussi bien chez l’homme que chez l’animal, à différents stades du développement de l’arthrose sur des paramètres variés. La gonarthrose est une maladie qui se caractérise par de nombreuses modifications des structures de l’articulation du genou. Ainsi, l’os sous chondral est particulièrement implique dans l’initiation ou la progression de l’arthrose. Les méthodes de diagnostic classiquement employées seront complétées par l’analyse de l’organisation des travées osseuses, par l’analyse de la densité minérale osseuse, par l’analyse microscopique de l’ostéocyte et des lacunes dans lesquelles il se trouve. Nos résultats démontrent que l’exercice a des effets positifs sur l’os sous chondral avec un meilleur contrôle de la minéralisation probablement via une augmentation de la viabilité des ostéocytes. / Knee injuries, such as anterior cruciate ligament rupture, occur frequently in sport or exercise. Mid-term or long-term consequence is an early osteoarthritis. If physical activity can be indirectly the cause of development of this disease, it is also a form of non-pharmacological therapy. The effects of exercise will be studied both in humans and animals at different osteoarthritis severity stages on various parameters. Knee osteoarthritis is a disease that is characterized by many changes in the structure of the joint. Thus, the subchondral bone is particularly involved in the initiation or progression of osteoarthritis. Diagnostic methods usually employed, will be complemented by the analysis of trabecular bone organization, analysis of bone mineral density, microscopic analysis of osteocytes and their lacunae in which they are embedded. Our results show that exercise has positive effects on subchondral bone with better control of the mineralization probably through an increase in the viability of osteocytes.

In conclusion, the present study firstly addressed the relationship between graft incorporation and peri-graft bone quality and quantity after ACL reconstruction in a rabbit model. The findings suggested that the non-invasive measurement of peri-graft bone would be useful to predict graft incorporation. Peri-graft bone loss was region-specific after surgery, which might be associated with stress shielding in the specific region after tunnel creation. The use of Brushite CPC might be a promising way to augment peri-graft bone and enhance graft incorporation. (Abstract shortened by UMI.) / In the fourth part, brushite CPC was successfully applied to augment the peri-tendon bone volume and connectivity. It was revealed under mechanical testing that the ultimate strength and stiffness of graft fixation in bone tunnel on experimental side was higher than that of the control by 117% and 102% respectively at 6 weeks, postoperatively (p&lt;0.05 for both). The use of brushite CPC caused a paradigm shift in failure mode from intra-tunnel to intra-articular portion at 12 weeks postoperatively (p=0.013). / Keywords. anterior cruciate ligament reconstruction, bone mass, microarchitecture, tendon-to-bone healing, graft incorporation, brushite calcium phosphate cement / The first part of this thesis compared the histological characteristics of T-B healing interface tissue in femoral and tibial tunnels following ACL reconstruction in rabbits. Results revealed that less cartilaginous interface tissue was formed in tibial tunnel than in femoral tunnel. Such cartilaginous tissue was gradually mineralized during reestablishment of a direct T-B integration. T-B healing in tibial tunnel was inferior to that in femoral tunnel. The disparity of T-B healing in various osseous milieus suggested the potential association in between. / The second part of this original work further explored the numeric relationship between the strength of T-B attachment and peri-graft bone mass and connectivity. Results of Micro-computed tomography (micro-CT) showed that peri-graft bone mass and connectivity was significantly lower on tibial side than those on femoral side. It was found under biomechanical evaluation that grafted tendon was prone to be pulled out from tibial tunnel with the bone attachment; the weakest point of the complexes shifted from the healing interface at time zero to peri-graft bone at week 6 after operation. With reverse of peri-graft bone at week 12 postoperatively, the weakest point shifted to intra-osseous tendinous portion. The stiffness of graft fixation correlated with peri-graft BV/TV (r2=0.68, p=0.001) and connectivity (r2=0.47, p=0.013) at week 6 after operation. / The third part addressed the changes of peri-graft bone in spatial and temporal manners using high resoluation multiple-slice peripheral quantitative computed tomography (pQCT) and micro-CT. Under pQCT evaluation, a decrease in BMD was present in specific regions, medial region of femoral tunnel by 26% and posterior and lateral regions of tibial tunnel by 22% and 42%, respectively at week 12 postoperatively than the baseline (p&lt;0.05 for all). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of plate-like to rod-like trabeculae and loss of anisotropy under micro-CT evaluation. It was echoed by histological findings showing increased osteoclastic activities and poor T-B healing in these specific regions. The postoperative bone loss and associated poor T-B healing was region-specific. / by Wen, Chunyi. / Adviser: Kai-ming Chan. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0217. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 148-168). / 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.

La cinématique de l’articulation du genou est complexe. Elle est déterminée par des paramètres géométriques et des paramètres mécaniques. Les paramètres géométriques sont principalement définis par la géométrie des os, des surfaces articulaires et par les insertions des différents tissus mous. Les paramètres mécaniques sont définis par les caractéristiques des tissus mous exprimés par les lois qui relient les distances entre leurs insertions et les efforts qu’ils génèrent. Les muscles, tendons et ligaments sont caractérisés par leur constante de raideur et leur pré-tension à une position donnée de l’articulation du genou : l’extension totale. Cette thèse analyse à l’aide d’un modèle multi-corps rigides le comportement de l’articulation du genou. La première partie de la thèse décrit la constitution du modèle. La seconde partie positionne le modèle dans des conditions aux limites. La troisième partie présente les résultats du modèle et les compare à différentes publications de la bibliographie. La quatrième et dernière partie fait varier les différents paramètres mécaniques et quantifie leur influence sur la cinématique du genou. Une synthèse des résultats permet de mettre en évidence les paramètres les plus influents sur la rotation interne/externe du tibia par rapport au fémur et sur l’avancée/recul du fémur par rapport au tibia pendant le mouvement de flexion du genou. / Knee kinematic is complex. It depends of geometric parameters and mechanical parameters. Geometric parameters are mainly defined by bone geometry, articular surfaces and by several soft tissues insertions. Mechanical parameters are defined by soft tissues characteristics designed by laws which link distances between their insertions and generated forces. Muscles, tendons, and ligaments are characterized by linear stiffness and pre-load at one specific position of knee joint: full extension. This work analyzes with rigid-body simulation tool, the knee joint comportment. First part of this work describes model construction. Second part places model inside external loads and constrains. Third part shows model results and compares them to several bibliographies. Last and forth part tests several values of each mechanical parameter. This part evaluates influence of parameter to knee kinematic. Synthesis of results helps to show most influent parameters on internal/external rotation of tibia relative to femur and on femur anterior/posterior displacement during knee flexion movement.

Le rachis est une structure ostéo-disco-ligamentaire complexe jouant un rôle majeur dans la stabilité et la mobilité du corps humain. Dans certaines conditions, des blessures traumatiques ou de fatigue peuvent survenir. Chaque année, plus de 700000 nouveaux traumas rachidiens sont comptabilisés au niveau mondial. Les blessures de fatigue, résultant d’une sur-sollicitation des structures vertébrales, sont fréquentes dans le domaine sportif. La spondylolyse est la blessure la plus commune parmi les blessures de fatigue dues au sport, notamment chez les adolescents. Cette thèse vise à améliorer la compréhension des mécanismes de blessures du rachis lombaire dans des conditions traumatiques et sportives en tenant compte des facteurs intrinsèques (posture, propriétés mécaniques des ligaments) et extrinsèques (conditions de chargement). Le volet expérimental décrit la caractérisation des ligaments du rachis thoracique et lombaire humain en traction uni-axiale dynamique. Le volet numérique porte sur l’analyse par éléments finis des pathomécanismes du rachis lombaire en conditions traumatiques, d’une part, et pour l’étude des risques de spondylolyse dans le domaine sportif d’autre part. Cette thèse a été réalisée en cotutelle entre Polytechnique Montréal et le Laboratoire de Biomécanique Appliquée (UMRT21 Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux/ Aix-Marseille Université) et s’inscrit dans les travaux de recherche du Laboratoire international – Imagerie et biomécanique du rachis (iLab-Spine) et de la Chaire de recherche industrielle CRSNG/Medtronic en biomécanique de la colonne vertébrale. / The spine is an osteo-disco-ligamentous structure playing a major role in the human body’s stability and mobility. In some conditions, traumatic or stress injuries may happen. Each year, more than 700,000 new traumatic injuries are diagnosed worldwide. Stress injuries result from overuse of spinal structures because of repetitive movements and sport practice is a common cause. The spondylolysis is the most common stress injuries due to sport activities, particularly in adolescents. The objective of this thesis was to improve the understanding of the lumbar injury mechanisms in traumatic and sport-related conditions taking into account intrinsic (posture, ligament mechanical properties) and extrinsic factors (loading conditions). The experimental part deals with the lumbar and thoracic ligament characterization under uni-axial dynamic tensile tests. The numerical part was performed to assess the pathomechanisms of the lumbar spine in traumatic conditions and related to the risk of spondylolysis in sport-related conditions. This project was done as a joint program between Ecole Polytechnique de Montreal and the Laboratoire de biomécanique appliquée (UMRT21 Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux/ Aix-Marseille Université) and was a part of the research work of the iLab-Spine (International Laboratory - Spine Imaging and Biomechanics) and the Industrial Research Chair program CRSNG/Medtronic on the spinal biomechanics.

Thesis (Ph. D.)--University of Oregon, 2001. / Includes vita and abstract. Includes bibliographical references (leaves 191-196). Also available for download via the World Wide Web; free to University of Oregon users.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 2 uppsatser.