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La compréhension de la biomécanique des structures articulaires est inhérente à l'amélioration de l'évaluation clinique de l'articulation coxo-fémorale. Cette articulation possède une capsule articulaire qui contient du liquide synovial et composée de ligaments capsulaires. Premièrement, le volume du liquide synovial peut être modifié en présence d'un problème articulaire. La pression intracapsulaire sera donc modifiée par ce changement de volume et par les mouvements articulaires effectués. Deuxièmement, les ligaments capsulaires s’allongent en fonction des différentes amplitudes articulaires. Les six degrés de liberté de mouvement de l'articulation coxo-fémorale rendent plus complexes l'évaluation et l'interprétation des pressions intracapsulaires et des allongements ligamentaires. À ce jour, les informations sur les pressions intracapsulaires et les allongements ligamentaires pendant les mouvements de l'articulation sont incomplètes ou limitées. La première étude visait à présenter les fluctuations des pressions intracapsulaires lors de cinq mouvements classiques au sein des compartiments capsulaire (latéral) et acétabulaire (médial). Latéralement, la pression est liée à l’amplitude articulaire. Médialement, la pression est beaucoup plus réactive aux mouvements. Cette première étude montre une variabilité importante entre les mouvements et les compartiments dans lesquels la pression est évaluée. La deuxième étude visait à rapporter les pressions dans les tests de provocation de flexion-abduction-rotation externe (FABER) et de flexion-adduction-rotation interne (FADIR). Lors du test de FABER, la pression intracapsulaire est négative dans les deux compartiments capsulaires. Pour le test de FADIR, la pression intracapsulaire est très élevée dans le compartiment latéral. Cette augmentation significative pourrait présenter une explication des problèmes de sensibilité et de spécificité du test de FADIR face à des modifications ostéologiques qui sont habituellement évaluées lors de son exécution. La troisième étude visait à présenter les allongements longitudinaux et transversaux du ligament iliofémoral lors de quatre mouvements articulaires soient l’abduction, la rotation externe et interne en extension et l’extension seule. Nos résultats montrent une hétérogénéité importante au sein des deux faisceaux du ligament iliofémoral lors de ces mouvements articulaires. La quatrième étude portait sur les allongements ligamentaires au sein du ligament iliofémoral lors du test de FABER. D’après nos résultats, il est possible d’observer des allongements significativement différents entre les faisceaux médial et latéral du ligament iliofémoral. Le faisceau latéral s’allonge dans sa globalité. L’allongement le plus important est observé dans la portion distale de ce faisceau. Médialement, le faisceau rétrécissait. Au regard de ces différents résultats entre les deux faisceaux, une distinction est nécessaire lors du test de FABER. En fait, ils auront des comportements complètement différents. En conclusion, ces quatre études portent sur l’analyse des pressions intracapsulaires et des allongements ligamentaires lors des mouvements classiques et des tests de provocation. Les différentes études montrent que la pression est dépendante du mouvement et du compartiment dans lequel elle est évaluée. Quant aux allongements, ceux-ci varient en regard du mouvement, de la portion et du faisceau dans lesquels ils sont évalués. Ces résultats soulignent l’importance de prendre en considération ces variations lors de l’évaluation clinique de la hanche. / Understanding tissue and joint biomechanics are inherent to improving the clinical evaluation of the coxofemoral joint. The coxofemoral joint has a joint capsule that contains synovial fluid and is composed of capsular ligaments. Firstly, the volume of synovial fluid can increase in the presence of a joint problem. The intra-articular pressure will therefore be modified by this change in volume and by the joint movements performed. Secondly, the capsular ligaments increase or decrease in length depending on the movement performed. The six degrees of freedom of movement of the coxofemoral joint make the assessment and interpretation of intra-articular pressures and ligament strains more complex. To date, information on intra-articular pressure and ligament strains during joint range of motion are incomplete or limited. The first study intended to present the fluctuations of intra-articular pressures during five classical movements within the capsular (lateral) and acetabular (medial) compartments. Laterally, the pressure is related to joint range of motion. Medially, the pressure is much more reactive. This study shows significant variability between movements and compartments in which the pressure is assessed. The second study aimed to report pressures in the flexion-abduction-external rotation (FABER) and flexion-adduction-internal rotation (FADIR) provocation tests. In the FABER test, the intra-articular pressure was negative in both capsular compartments. For the FADIR test, the intra-articular pressure was very high in the lateral compartment. This significant increase could present an explanation for the sensitivity and specificity problems of the FADIR test in the face of osteological changes. The third study aimed to present the longitudinal and transverse strains of the iliofemoral ligament during four joint movements, namely abduction, external and internal rotation in extension and extension alone. Our results show significant heterogenity within the two bands of the iliofemoral ligament during these joint movements. The fourth study looked at ligament strains within the iliofemoral ligament during the FABER test. According to our results, it is possible to observe significantly different strains between the medial and lateral bands of the iliofemoral ligament. The lateral band increase in length globally. The largest strain was observed in the distal portion of this band. Medially, the band decreases in length. In view of these different results between the two bands, it is important to distinguish them when performing the FABER test as they will have completely different behaviors. In conclusion, these four studies describe the analysis of intra-articular pressures and ligament strains during the classical movement and provocation test. They show that the pressure is dependent on the movement and the compartment in which it is assessed. As for ligament strains, they vary according to the movement, the portion, and the band in which they are evaluated. These results underline the importance of taking these variations into consideration during the clinical evaluation of the hip.

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.

O escorregamento epifisário proximal do fêmur (EEPF) é a afecção do quadril mais comum na adolescência e se caracteriza pela excentricidade da epífise em relação à metáfise. Deformidades anatômicas residuais e efeitos secundários no mecanismo abdutor podem estar associados à perda de força abdutora. Objetivamos avaliar a função da musculatura abdutora do quadril após tratamento cirúrgico com osteotomia femoral basocervical e cervicoplastia e comparar os resultados com indivíduos saudáveis. Vinte e quatro pacientes com EEPF moderado ou grave foram submetidos à osteotomia femoral basocervical e cervicoplastia entre 2012 e 2015, e foram avaliados prospectivamente com seguimento mínimo de um ano (idade média 14,9 ± 1,6 anos). O grupo controle foi composto por 15 indivíduos saudáveis sem sintomas no quadril (16,5 ± 2,5 anos). Avaliamos a amplitude de abdução passiva dos quadris, força concêntrica dos músculos abdutores do quadril por meio de dinamometria isocinética a 60°/s e a 120°/s, teste de Trendelenburg, e a pontuação dos questionários Harris Hip Score (HHS) e 12-Item Short-Form Health Survey (SF-12). Um subgrupo de sete pacientes foi submetido à avaliação longitudinal aos seis, 12 e 24 meses de pós-operatório. No seguimento final, comparamos a função abdutora dos quadris com escorregamentos moderados e graves submetidos à osteotomia basocervical e cervicoplastia, com escorregamentos contralaterais mais leves, submetidos à fixação in situ, quadris contralaterais sem EEPF, e grupo controle. No subgrupo avaliado longitudinalmente, houve melhora significativa na força muscular abdutora dos quadris durante os dois anos de seguimento (60º/s, p=0,048; 120º/s, p=0,001). O seguimento final médio de todos os pacientes foi de 1,6 ± 0,6 anos. Quadris com EEPF apresentaram a média de pico de torque abdutor diminuída quando comparados aos quadris contralaterais sem escorregamento (60º/s, p=0,004; 120º/s, p<0,001) e aos quadris dos indivíduos controles (60º/s, p<0,001; 120º/s, p<0,001). Após a osteotomia basocervical e cervicoplatia, os quadris apresentaram média de pico de torque abdutor (60°/s, p=0,63; 120º/s, p=0,99) e amplitude de abdução passiva (p=0,5) semelhante aos quadris fixados in situ. Houve correlação positiva significativa entre médias de pico de torque abdutor e a amplitude de abdução passiva do quadril (coeficiente de Spearman, 0,36; p<0,001). O sinal de Trendelenburg foi ausente em 91,6% dos pacientes no tempo final de seguimento. As médias das pontuações dos questionários dos pacientes no seguimento final foram de 94.8 ± 7.3 para o HHS; 52.6 ± 6.8 e 57.6 ± 4.6 para os componentes físico e mental do SF-12, respectivamente. Concluímos que o restabelecimento de força de mecanismo abdutor é progressivo nos dois anos após osteotomia basocervical e cervicoplastia, porém a força não foi restabelecida aos níveis normais. Um ano não foi suficiente para recuperação da força abdutora. Os resultados da osteotomia basocervical realizada em quadris com EEPF moderado e grave foram comparáveis aos resultados de quadris com desvio inicial significativamente menores submetidos à fixação in situ. / Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescence and is characterized by the eccentricity of the epiphysis in relation to the metaphysis. The condition is associated with loss of abductor strength as a consequence of residual anatomical deformities and secondary effects in the abductor mechanism. We aimed to evaluate the abductor muscle function after the surgical treatment with basicervical femoral osteotomy and head-neck osteochondroplasty, comparing with healthy control individuals. Twenty-four patients with moderate or severe SCFE underwent basocervical femoral osteotomy and osteochondroplasty between 2012 and 2015, and were prospectively evaluated with a minimum follow-up of one year (mean age: 14.9 ± 1.6 years). The control group consisted of 15 individuals without hip symptoms (16.5 ± 2.5 years). We evaluated the passive range of hip abduction, concentric strength of the hip abductor muscles by means of isokinetic dynamometry at 60°/s and 120°/s, Trendelenburg test, Harris Hip Score (HHS) and 12-item short-form health survey (SF-12). A subset of seven patients underwent to longitudinal evaluation at six, 12 and 24 postoperative months. At the final follow-up, we compared the abductor function of the hips with moderate and severe slips submitted to basocervical osteotomy and cervicoplasty, with less severe contralateral slips submitted to in situ fixation, contralateral hips without SCFE, and control group. The subgroup assessed longitudinally had a significant improvement in the abductor muscular strength of the hips during two years of follow-up (60º/s, p = 0.048, 120º/s, p = 0.001). The mean final follow-up of all patients was 1.6 ± 0.6 years. The mean peak abductor torque was decreased in hips with SCFE when compared to the contralateral non-slip side (60º/s, p = 0.004; 120º/s, p <0.001); and control individuals (60º/s, p<0.001; 120º/s, p<0.001). After a basicervical osteotomy and osteochondroplasty, hips had a mean abductor torque (60º/s, p=0.63; 120º/s, p=0.99) and range of abduction (p=0.5) similar to hips pinned in situ. Abduction strength had significant positive correlation with the passive range of abduction (Spearman\'s coefficient, 0.36; p<0.001).The Trendelenburg signal was absent in 91.6% of the patients at the final follow-up. The mean HHS at the final follow-up was 94.8 ± 7.3; and the physical and mental components of the SF-12 were 52.6 ± 6.8 and 57.6 ± 4.6. We conclude that the restoration of abductor strength is progressive in two years following basicervical osteotomy and osteochondroplasty. One year was not enough for the restoration of the abductor strength. The outcomes of the basicervical osteotomy performed in hips with moderate and severe SCFE were comparable to in situ fixation performed in much less severe slips.

The mevalonate pathway is an important biosynthetic pathway, found in all cells of virtually all known pro- as well as eukaryotic organisms. This thesis is an investigation into the use of two drugs, originally developed for different applications, but both affecting the mevalonate pathway, in to models of fracture repair. Using two different rodent models of fracture repair, a commonly used cholesterol lowering drug (statin) and two drugs used to treat osteoporosis (bisphosphonate) were applied both systemically as well as locally in order to enhance fracture repair. Papers I and II investigate the potential of simvastatin to improve the healing of femoral fractures in mice. Papers III and IV explore the use of two bisphosphonates to improve early fixation of stainless steel screws into rat bone. The statin simvastatin lead to an increased strength of the healing cellus. The application of bisphosphonates increased early screw fixation. It seems clear that both drugs have uses in orthopaedic applications. One interesting avenue of further research would be to combine the two classes of drugs and see if we can get the benefits while at the same time diminishing the drawbacks.

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Transplanting bone graft from one site in the patient to the site of fracture or bone void, i.e. autologous bone grafting is commonly used throughout the world. The transplanted bone not only fills voids, but is also bone inductive, housing the particular cells that are needed for bone regeneration. Nevertheless, a regenerative complement to autograft is of great interest and importance because the benefits from an off-the-shelf product with as good of healing capacity as autograft will circumvent most of the drawbacks with autograft. With a regenerative-medicine approach, the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of limited volume of material. Two such regenerative products that utilize bone morphogenetic protein 7 and 2 have been used for more than a decade in the clinic. However, some severe side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery, use of supra physiological doses of the BMPs due to poor localization and retention of the growth factors. The purpose of this thesis was to harness the strong inductive capability of the BMP-2 by optimizing the carrier of this bioactive protein, thereby minimizing the side effects that are associated with the clinical products and facilitating safe and localized bone regeneration at the desired site. We focused on an injectable hyaluronan-based carrier. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident hyaluronidase enzymes. Earlier studies have shown a more controlled release and improved mechanical properties when adding a weight of 25 percent of hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that the bone formation was enhanced when using nano-sized hydroxyapatite. We wished to further develop the carrier system but were lacking an animal model with high output and easy access. We also wanted to provide paired data and were committed to the 3 Rs of refinement, reduction and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper II. In Paper III, we characterized and optimized the handling properties of the carrier. In Paper IV, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. In Paper V, we sought to further optimize biomaterial properties of the hydrogel through covalently bonding of bisphosphonates to the hyaluronan hydrogel. The results demonstrated exceptional retention of the growth factor BMP-2. In Paper VI, the in vivo response related to the release of the growth factor was examined by combining a SPECT/PET/µCT imaging method to visualize both the retention of the drug, and the in-vivo response in terms of mineralization.

1 Abstract The aim is to investigate whether the distal femoral cartilage (DFC), Achilles tendon (AT) and plantar fascia (PF) were different between healthy young women wearing high-heel shoes (HHS) (> 5 cm) and flat shoes (< 1.4 cm). Measurements from aforementioned structures were obtained by using ultrasound. There were 910 measurement parameters analyzed in total. There were 34 women in the HHS group (mean age 31.1±6.4 years; BMI 21.6 ± 2.3 kg/m2 ) and 57 women in the control group (mean age; 29.5 ± 7.3 years; BMI 22.5 ± 3.4 kg/m2 ). Wearing HHS resulted in thickening of the right medial DFC (2.00 ± 0.41 mm) and left AT (4.07 ± 0.48 mm) in women wearing HHS compared to flat shoes (1.96 ± 0.35 mm, 3.76 ± 0.66 mm, respectively). This might be interpreted as secondary to chronic overload. PF thicknesses were similar both within and between group. Our findings have shown significant thickening of the right medial DFC and left AT in women wearing HHS and these changes might be interpreted as secondary to chronic overload. Further follow-up studies are definitely awaited to provide a better insight into understanding the musculoskeletal consequences of this "social" issue ever-existing in ladies lives. The secondary aim of the thesis comprises two case reports: 1. the first is describing the usefulness of MSK...

Made available in DSpace on 2016-06-02T20:18:20Z (GMT). No. of bitstreams: 1 TeseJSB.pdf: 1248166 bytes, checksum: 2327b08724c3471ad628a8f9fb5ff44d (MD5) Previous issue date: 2004-12-10 / Financiadora de Estudos e Projetos / The anterior cruciate ligament (ACL) is the most commonly injured ligament in the knee and its rupture results in pain, instability, muscle atrophy and weakness. The quadriceps femoris muscle dysfunction is common before and after ACL reconstruction and can persist over years. A detailed understanding of neuromuscular function after ACL reconstruction is critical to the development of optimal rehabilitation strategies. The purpose of this study was to investigate the contributions of functional and morphological factors, in the muscle recovery, after ACL reconstruction. The effects of two therapeutic methods, usually utilized to recover muscle strength were also evaluated: Neuromuscular Electrical Stimulation (NMES) and eccentric exercise. Eight subjects (age = 31.3 ± 5.8 years) who had undergone ACL ligament reconstruction (mean 9.4 ± 0.7 months after the surgery) were randomly assigned to either an eccentric exercise associated with NMES (russian current) or only an eccentric exercise group. Only the involved limb was trained 2 days a week, for 12 weeks. The uninvolved one was also evaluated as reference. The quadriceps muscle function was evaluated by the measurement of the knee extensor torque during isometric and eccentric isokinetic contractions (30 and 120º/s) and by surface electromyography (EMG) of the Vastus Medialis Obliquos (VMO), Vastus Lateralis (VL) and Rectus Femoris (RF) muscles. The quadriceps cross-sectional area (CSA) was measured in six regions using Nuclear Magnetic Resonance Imaging (MRI-I). The initial evaluation showed significant extensor torque deficit both in isometric and eccentric conditions of the involved limb, compared to the contralateral one. There was significant muscle atrophy along the quadriceps extension, mainly in the distal thigh region. The EMG activity was lower for the VMO in all tested situations. NMES did not interfere in the gain of muscular strength, in any of the evaluated functions. The eccentric training increased significantly the isometric (from 198 ± 37 to 228 ± 48 Nm, p<0.05) and eccentric torque at 30 and 120º/s (from 227 ± 56 to 291 ± 65, p< 0.01 and from 199 ± 51 to 240 ± 63, p< 0.05, respectively). Quadriceps cross-sectional area also increased at all the evaluated regions for the involved limb, and the highest hypertrophy was at the thigh proximal region (from 169 ± 27 to 189 ± 25,8 cm2, p< 0.01 ), when compared to the distal region (form 31,5 ± 5,9 to 35,1 ± 6,1 cm2, p< 0.01). The EMG activity of VMO was recovered after the first six weeks of eccentric training. In the same period, the increased extensor torque showed correlation with the increased quadriceps cross-sectional area (r=0,81) and with the recovery of motor unit activation (r=0.69). After twelve weeks of training, there was correlation only between increased torque and cross-sectional area (r=0.78). In conclusion: 1) eccentric training showed to be a potent resource in the recovery of both morphological and functional factors of quadriceps, after ACL reconstruction; 2) NEMS did not interfere in the rehabilitation of these individuals. / O Ligamento Cruzado Anterior (LCA) é o mais freqüentemente ligamento lesado do joelho e a sua ruptura resulta em dor, instabilidade, atrofia e fraqueza muscular. A disfunção do músculo quadríceps é comum antes e após a reconstrução do LCA, podendo persistir por anos. Um detalhado conhecimento da função neuromuscular após reconstrução do LCA é crítico para a otimização das estratégias de reabilitação. O propósito deste estudo foi avaliar as contribuições dos fatores funcionais e morfológicos na recuperação da força muscular, após reconstrução do LCA. Os efeitos de dois métodos terapêuticos usualmente utilizados na reabilitação também foram avaliados: a Estimulação Elétrica Neuromuscular (EENM) e o exercício excêntrico. Oito indivíduos (31.3 ± 5.8 anos) os quais foram submetidos a reconstrução do LCA (média de 9.4 ± 0.7 meses de pós-operatório) foram aleatoriamente designados para o grupo exercício excêntrico com EENM (utilizando a corrente russa) ou apenas exercício excêntrico. Apenas o membro envolvido foi treinado, 2 vezes por semana, durante 12 semanas. O membro não envolvido foi avaliado como referência. A função do músculo quadríceps foi avaliada por medidas do torque extensor do joelho durante contrações isométricas e isocinéticas excêntricas (30 e 120º/s) e por meio da eletromiografia (EMG) de superfície dos músculos Vasto Medial Oblíquo (VMO), Vasto Lateral (VL) e Reto Femoral. A Área de Secção Transversa (AST) do quadríceps foi mensurada em seis regiões, por meio de imagens de Ressonância Nuclear Magnética (RNM). A avaliação inicial demonstrou significativo déficit no torque extensor do membro acometido, quando comparado ao não acometido, tanto nas avaliações isométricas como nas excêntricas. Houve significativa atrofia muscular ao longo do quadríceps, sobretudo na região distal. A atividade EMG mostrou-se reduzida no VMO, em todas as situações avaliadas. A EENM não interferiu no ganho de força muscular, em nenhuma das funções mensuradas. O treinamento excêntrico aumentou significativamente o torque isométrico (de 198 ± 37 para 228 ± 48 Nm, p<0.05) e excêntrico em 30 e 120º/s (de 227 ± 56 para 291 ± 65, p< 0.01 e de 199 ± 51 para 240 ± 63, p< 0.05, respectivamente). A área de secção transversa também aumentou em todas as regiões avaliadas do membro acometido, sendo que a maior hipertrofia ocorreu na região proximal da coxa (de 169 ± 27 para 189 ± 25,8 cm2, p< 0.01), quando comparada a região distal (de 31,5 ± 5,9 para 35,1 ± 6,1 cm2, p< 0.01). A atividade EMG do VMO foi recuperada após as primeiras seis semanas de treinamento excêntrico. No mesmo período, o aumento no torque extensor demonstrou correlação direta com o aumento na área de secção transversa (r=0.81) e com a recuperação na ativação das unidades motoras (r=0.69). Após doze semanas de treinamento, houve correlação apenas entre o aumento do torque e a área de secção transversa (r=0.78). Em conclusão: 1) o treinamento excêntrico mostrou-se um potente recurso tanto na recuperação dos fatores morfológicos como funcionais do músculo quadríceps, após reconstrução do LCA; 2) a EENM não interferiu na reabilitação desses indivíduos.