Manufacturing conditioned roughness and wear of biomedical oxide ceramics for all-ceramic knee implants

Background: Ceramic materials are used in a growing proportion of hip joint prostheses due to their wear resistance and biocompatibility properties. However, ceramics have not been applied successfully in total knee joint endoprostheses to date. One reason for this is that with strict surface quality requirements, there are significant challenges with regard to machining. High-toughness bioceramics can only be machined by grinding and polishing processes. The aim of this study was to develop an automated process chain for the manufacturing of an all-ceramic knee implant. Methods: A five-axis machining process was developed for all-ceramic implant components. These components were used in an investigation of the influence of surface conformity on wear behavior under simplified knee joint motion. Results: The implant components showed considerably reduced wear compared to conventional material combinations. Contact area resulting from a variety of component surface shapes, with a variety of levels of surface conformity, greatly influenced wear rate. Conclusions: It is possible to realize an all-ceramic knee endoprosthesis device, with a precise and affordable manufacturing process. The shape accuracy of the component surfaces, as specified by the design and achieved during the manufacturing process, has a substantial influence on the wear behavior of the prosthesis. This result, if corroborated by results with a greater sample size, is likely to influence the design parameters of such devices.

Distal limb osteoarthritis in the horse

The aim of this thesis was to study two objective methods of osteoarthritis (OA) diagnosis in horses and use them on the assessment of new intra-articular treatments. The studied methods were a new inertial-sensor based system of lameness detection and cartilage biomarkers in serum. It was found that distal limb flexion is significantly correlated to the presence of metacarpo-phalangeal OA in hind limbs and that inertial-sensors are sensitive in detecting asymmetry in these cases. A positive and significant correlation was observed between Coll2-1 concentration in serum and the presence of joint disease in males and young horses. Fib3-2 measurement has good potential to be used since it is not influenced by sex or age. Using an experimental model of OA, adipose stem cells pre-activated with interferon-gamma decreased joint inflammation and radiographic lesions. In clinical cases, a single injection of high-concentrated and high-molecular weight hyaluronic-acid decreased joint inflammation and biomarkers’ concentration; OSTEOARTRITE DO MEMBRO DISTAL NO CAVALO Resumo: A finalidade desta tese foi estudar dois métodos de diagnóstico objetivo de osteoartrite (OA) em equinos e aplicá-los na avaliação de novas terapias intra-articulares. Utilizou-se um sistema de sensores de movimento e foi avaliada a concentração de biomarcadores de cartilagem no soro. Concluiu-se que a flexão distal positiva está correlacionada com OA na articulação metacarpofalângica nos membros posteriores e que os sensores são sensíveis na detecção de assimetria nestes casos. Existe uma correlação positiva e significativa entre as concentrações de Coll2-1 e a presença de doença articular, sobretudo em machos e jovens. A dosagem de Fib3-2 tem utilidade por não ser influenciada pelo sexo nem idade. Num modelo experimental da doença, a terapia à base de células estaminais reduziu a inflamação articular e as lesões radiográficas. Em casos clínicos, o tratamento com ácido-hialurónico de alta concentração e peso molecular provoca uma diminuição da inflamação articular e dos biomarcadores no soro.

A rolling-gliding wear simulator for the investigation of tribological material pairings for application in total knee arthroplasty

Background: Material wear testing is an important technique in the development and evaluation of materials for use in implant for total knee arthroplasty. Since a knee joint induces a complex rolling-gliding movement, standardised material wear testing devices such as Pin-on-Disc or Ring-on-Disc testers are suitable to only a limited extent because they generate pure gliding motion only.Methods: A rolling-gliding wear simulator was thus designed, constructed and implemented, which simulates and reproduces the rolling-gliding movement and loading of the knee joint on specimens of simplified geometry. The technical concept was to run a base-plate, representing the tibia plateau, against a pivoted cylindrical counter-body, representing one femur condyle under an axial load. A rolling movement occurs as a result of the friction and pure gliding is induced by limiting the rotation of the cylindrical counter-body. The set up also enables simplified specimens handling and removal for gravimetrical wear measurements. Long-term wear tests and gravimetrical wear measurements were carried out on the well known material pairings: cobalt chrome-polyethylene, ceramic-polyethylene and ceramic-ceramic, over three million motion cycles to allow material comparisons to be made.Results: The observed differences in wear rates between cobalt-chrome on polyethylene and ceramic on polyethylene pairings were similar to the differences of published data for existing material-pairings. Test results on ceramic-ceramic pairings of different frontal-plane geometry and surface roughness displayed low wear rates and no fracture failures.Conclusions: The presented set up is able to simulate the rolling-gliding movement of the knee joint, is easy to use, and requires a minimum of user intervention or monitoring. It is suitable for long-term testing, and therefore a useful tool for the investigation of new and promising materials which are of interest for application in knee joint replacement implants. © 2010 Richter et al; licensee BioMed Central Ltd.

A double blind trial of ketoprofen in the treatment of osteoarthritis of the hip

In a double blind study of ketoprofen and placebo in the treatment of osteoarthritis of the hip, ketoprofen was shown to be significantly more effective. Analysis of results was made using the sequential technique. Major intolerance occurred in two cases and minor intolerance in five cases. Newly diagnosed cases were treated more readily with ketoprofen than chronic cases treated for several months with other drugs which had proved ineffective. There were no changes in biological parameters. Age and sex did not affect the result. The further study of ketoprofen in large open trials appears to be indicated.

Medial and lateral hamstrings and quadriceps co-activation affects knee joint kinematics and ACL elongation : a pilot study

Kinematic and electromyographic analysis of the overhead squat in individuals showing excessive medial knee displacement

Dynamic knee valgus is a multi-planar motion that has been associated with anterior cruciate ligament injuries and patellofemoral pain syndrome. Clinical assessment of dynamic knee valgus can be made by looking for the visual appearance of excessive medial knee displacement (MKD) in the double-leg squat (DLS). The purpose of this dissertation was to identify the movement patterns and neuromuscular strategies associated with MKD during the DLS. Twenty-four control subjects and eight individuals showing MKD during the DLS participated in the study. Significant differences were verified between subjects that demonstrated MKD and a control (CON) group for the eletromyographic amplitude of adductor magnus, biceps femoris, vastus lateralis and vastus medialis muscles (p < 0.05), during the descending phase of the DLS. During the ascending phase were found group differences for adductor magnus and rectus femoris muscles (p < 0.05). Results from kinematic analysis revealed higher minimum and maximum values of ankle abduction and knee internal rotation angles (p < 0.05) for the MKD group. Also, individuals showing excessive MKD had higher hip adduction/abduction excursion. Our results suggested that higher tibial internal rotation and knee internal rotation angles in the initial position of the DLS are associated with MKD. The neuromuscular strategies that contributed to MKD were higher adductor magnus activation, whereas biceps femoris, vastus lateralis and vastus medialis activated more to stabilize the knee in response to the internal rotation moment.

Rôle de la signalisation Wnt non-canonique dans l’étiologie de l’ostéoarthrose chez l’humain

Les études cliniques et in vitro suggèrent que la sclérose de l’os sous-chondral due aux ostéoblastes (Ob) anormaux est impliquée dans la progression de l’ostéoarthrose (OA). Les Ob OA humains isolés à partir d’os sous-chondral sclérosé montrent un phénotype altéré, un niveau réduit de signalisation Wnt/β-caténine canonique et une minéralisation in vitro réduite. Il existe également deux voies non-canoniques, Wnt/PKC et Wnt/PCP qui ont étés décrites dans la littérature. Cependant, il n’existe aucune étude qui traite de ces deux voies dans les Ob OA. Ces voies sont activées après qu’un ligand Wnt non-canonique tel que Wnt-5a se lie à un récepteur Wnt couplé à des corécepteurs de la voie non-canonique. Ceci enclenche, respectivement pour la voie Wnt/PKC-Ca2+ et Wnt/PCP, la phosphorylation de PKC (p-PKC) et la phosphorylation de JNK (p-JNK) et agit sur les cibles en aval. Nous avons voulu déterminer s’il était possible de constater des altérations dans les voies Wnt non-canoniques dans les Ob OA. Nous avons préparé des cultures primaires d’ostéoblastes sous-chondral humains à partir de plateaux tibiaux de patients OA subissant une arthroplastie totale du genou, ainsi qu’à partir de plateaux tibiaux recueillis à l’autopsie de patients « normaux ». L’expression des gènes impliqués dans les voies Wnt/PKC et Wnt/PCP a été évaluée par RT-qPCR et la production par Western Blot des protéines, ainsi que celle de p-PKC et p-JNK et que l’activité des facteurs NFAT et AP-1 utilisés par ces deux voies. L’activité phosphatase alcaline (ALPase) et la quantité d’ostéocalcine (OC) ont étés évaluées respectivement à l’aide d’hydrolyse de substrat et d’ELISA. Le niveau de minéralisation a été évalué par la coloration au rouge Alizarine. Nos résultats montrent que l’expression et la production de Wnt-5a étaient augmentées dans les Ob OA comparées aux Ob N et LGR5 était significativement plus élevée. De plus, l’expression de LGR5 est directement régulée via la stimulation ou la diminution de Wnt-5a, à la fois au niveau de l’ARNm et des protéines. Par ailleurs, Wnt-5a a stimulé la phosphorylation de JNK et de PKC ainsi que l’activité NFAT et AP-1. Les niveaux de minéralisation ainsi que d’activité ALPase et de sécrétion d’OC ont aussi été affectés par les changements du niveau de Wnt-5a. Ces résultats suggèrent que Wnt-5a, qui est augmentée dans les OA Ob, peut stimuler les voies Wnt non-canoniques et affecter le phénotype et la minéralisation des OA Ob humains.

Rôle de la signalisation Wnt non-canonique dans l’étiologie de l’ostéoarthrose chez l’humain

Les études cliniques et in vitro suggèrent que la sclérose de l’os sous-chondral due aux ostéoblastes (Ob) anormaux est impliquée dans la progression de l’ostéoarthrose (OA). Les Ob OA humains isolés à partir d’os sous-chondral sclérosé montrent un phénotype altéré, un niveau réduit de signalisation Wnt/β-caténine canonique et une minéralisation in vitro réduite. Il existe également deux voies non-canoniques, Wnt/PKC et Wnt/PCP qui ont étés décrites dans la littérature. Cependant, il n’existe aucune étude qui traite de ces deux voies dans les Ob OA. Ces voies sont activées après qu’un ligand Wnt non-canonique tel que Wnt-5a se lie à un récepteur Wnt couplé à des corécepteurs de la voie non-canonique. Ceci enclenche, respectivement pour la voie Wnt/PKC-Ca2+ et Wnt/PCP, la phosphorylation de PKC (p-PKC) et la phosphorylation de JNK (p-JNK) et agit sur les cibles en aval. Nous avons voulu déterminer s’il était possible de constater des altérations dans les voies Wnt non-canoniques dans les Ob OA. Nous avons préparé des cultures primaires d’ostéoblastes sous-chondral humains à partir de plateaux tibiaux de patients OA subissant une arthroplastie totale du genou, ainsi qu’à partir de plateaux tibiaux recueillis à l’autopsie de patients « normaux ». L’expression des gènes impliqués dans les voies Wnt/PKC et Wnt/PCP a été évaluée par RT-qPCR et la production par Western Blot des protéines, ainsi que celle de p-PKC et p-JNK et que l’activité des facteurs NFAT et AP-1 utilisés par ces deux voies. L’activité phosphatase alcaline (ALPase) et la quantité d’ostéocalcine (OC) ont étés évaluées respectivement à l’aide d’hydrolyse de substrat et d’ELISA. Le niveau de minéralisation a été évalué par la coloration au rouge Alizarine. Nos résultats montrent que l’expression et la production de Wnt-5a étaient augmentées dans les Ob OA comparées aux Ob N et LGR5 était significativement plus élevée. De plus, l’expression de LGR5 est directement régulée via la stimulation ou la diminution de Wnt-5a, à la fois au niveau de l’ARNm et des protéines. Par ailleurs, Wnt-5a a stimulé la phosphorylation de JNK et de PKC ainsi que l’activité NFAT et AP-1. Les niveaux de minéralisation ainsi que d’activité ALPase et de sécrétion d’OC ont aussi été affectés par les changements du niveau de Wnt-5a. Ces résultats suggèrent que Wnt-5a, qui est augmentée dans les OA Ob, peut stimuler les voies Wnt non-canoniques et affecter le phénotype et la minéralisation des OA Ob humains.

EVIDENCE FOR MECHANICAL STRAINS INFLUENCE IN OSTEOPHYTE DEVELOPMENT

Purpose: Osteophytes are osteo-cartilaginous metaplastic tissue outgrowths of bone capped by cartilage usually found in degenerative and inflammatory joint disease. The presence and degree of maturity of osteophytes, along with joint space narrowing, are the main radiographic criteria for diagnosis and grading osteoarthritis (OA). Although osteophytes are known for being anatomic signs of advanced OA, they can occur in non-symptomatic joints, in joints with no other observable alterations, and in early stage OA. It remains unclear if they develop from molecular, physiological and/or mechanical stimuli. We hypothesized that mechanical strains play a role in osteophyte development. The overall objective of this thesis was to find evidence that osteophytes are influenced by mechanical strains. Methods: The first project was to develop a mechanically-induced osteophyte animal model. One single impact load that was reported to induce moderate joint damage was applied to the periosteum of the rat knee. Animals were sacrificed at four time points to characterize the evolution of damaged tissue and the joint by histology. A second study using human mature hip osteophytes was conducted to evaluate if mature osteophyte presented histological signs of proliferating and developmental processes. The histological characterization of mature osteophyte was used to compare findings of the mechanically-induced osteophyte in the animal model to validate the use of this rodent model in studying some aspect of osteophyte development of human. Lastly, a detailed three-dimensional (3D) radiological morphometric analysis was performed on microscopic computed tomography (µCT) scanned femoral heads collected from total hip arthroplasty patients presenting mature hip osteophytes. Quantitative morphometric measures of osteophytes internal structure was compared to three regions of the femoral head of known quality of organisation and mechanical constraint. Results and Conclusion: Osteophyte can be mechanically induced by a single load impact to the joint periosteum, indicating that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development. Mature osteophytes have proliferation, developing and remodelling zones and have trabecular structures. Mechanically-induced osteophytes and mature osteophytes presented similar histological composition. Mature osteophytes have organized internal structure. These results provide evidence that mechanical strain can influence osteophyte development.

Design of a myofascial therapy protocol for the treatment of hemophilic arthropathy of the knee and ankle

Hemophilic arthropathy limits daily life activities of patients with hemophilia, presenting with clinical manifestations such as chronic pain, limited mobility, or muscular atrophy. Although physical therapy is considered essential for these patients, few clinical studies have demonstrated the efficacy and safety of the various physiotherapy techniques. Physical therapy may be useful for treating hemophilic arthropathy by applying safe and effective techniques. However, it is necessary to create protocols for possible treatments to avoid the risk of bleeding in these patients. This article describes the musculoskeletal pathology of hemophilic arthropathy and characteristics of fascial therapy. This systematic protocol for treatment by fascial therapy of knee and ankle arthropathy in patients with hemophilia provides an analysis of the techniques that, depending on their purpose and methodology, can be used in these patients. Similarly, the protocol's applicability is analyzed and the steps to be followed in future research studies are described. Fascial therapy is a promising physiotherapy technique for treating fascial tissue and joint contractures in patients with hemophilic arthropathy. More research is needed to assess the efficacy and safety of this intervention in patients with hemophilia, particularly with randomized multicenter clinical trials

The role of chondrocyte senescence in the pathogenesis of canine osteoarthritis

The aims of this study were to (1) evaluate cellular senescence in chondrocytes from osteoarthritic articular cartilage, (2) investigate the hypothesis that oxidative stress is a feature of canine OA chondrocytes and that oxidative stress contributes to cellular senescence in canine chondrocytes, (3) investigate the hypothesis that osteoarthritic chondrocytes alter the gene expression of adjacent normal chondrocytes in OA joints leading to modulation of genes known to play a role in the pathogenesis of OA and (4) evaluate the presentation of dogs undergoing femoral head excision in veterinary referral practice in the UK as a treatment for osteoarthritis of the coxofemoral joint, and to categorise the distribution and severity of associated pathological lesions. Chondrocytes from osteoarthritic and normal cartilage were examined for levels of senescence. Initially chondrocytes were cultured using an alginate bead culture system, thought to mimic the extracellular matrix of articular cartilage. However, these chondrocytes showed almost no growth as compared to monolayer culture where they grew rapidly. OA chondrocytes entered the senescent state after 1.5 to 4.9 population doublings in monolayer culture, while normal chondrocytes underwent 4.8 to 14.6 population doublings before entering the senescent state. Osteoarthritic chondrocytes had increased levels of markers of cellular senescence (senescence associated beta-galactosidase accumulation and p16 protein accumulation) as compared to normal chondrocytes, suggesting that chondrocyte senescence is a feature of canine osteoarthritis. An experimental model for the induction of oxidative stress in chondrocyte cell culture was developed using tert-Butyl hydroperoxide and total cellular glutathione was measured as an indicator of cellular oxidative stress levels. Experimental induction of oxidative stress in both normal and osteoarthritic chondrocytes in cell culture resulted in increased amounts of cellular senescence, shown by an increase in levels of senescence associated beta-galactosidase accumulation and decreased replicative capacity. Experimental induction of oxidative stress also resulted in altered gene expression of three genes important to the degradation of the extracellular matrix; MMP-13, MMP-3 and Col-3A1, measured by RT-PCR, in normal canine chondrocytes in monolayer cell culture. MMP-3 showed the greatest relative expression change, with a fold-change of between 1.43 and 4.78. MMP-13 had a fold change of 1.16 to 1.38. Col-3A1 was down regulated, with a fold-change of between 0.21 and 0.31. These data demonstrate that experimentally induced oxidative stress in chondrocytes in monolayer culture increases levels of cellular senescence and alters the expression of genes relevant to the pathogenesis of canine OA. Coculture of osteoarthritic chondrocytes with normal canine chondrocytes resulted in gene modulation in the normal chondrocytes. Altered gene expression of ten genes known to play a role in the pathogenesis of osteoarthritis was detected in the normal chondrocytes (fold change shown in brackets); TNF-alpha (11.95), MMP-13 (5.93), MMP-3 (5.48), IL-4 (7.03), IL-6 (5.3), IL-8 (4.92), IL-F3 (4.22), COL-3A1 (4.12), ADAMTS-4 (3.78) and ADAMTS-5 (4.27). In total, 594 genes were significantly modulated suggesting that osteoarthritic chondrocytes contribute to the disease propagation by altering the gene expression of adjacent normal chondrocytes, thus recruiting them into the disease process. Gene expression changes were measured by microarray analysis and validated by RT-PCR and Western blot analysis. An epidemiological study of femoral heads collected from dogs undergoing total hip replacement surgery as a treatment for osteoarthritis of the coxofemoral joint secondary to canine hip dysplasia revealed that there was no characteristic pattern of cartilage lesion for canine hip dysplasia. Severe pathology of the femoral head with cartilage erosion occurred in 63.9% of cases and exposure of subchondral bone in 31.3% of cases. The work presented in this thesis has demonstrated that cellular senescence is a feature of chondrocytes from canine osteoarthritic cartilage and suggests that cellular senescence and oxidative stress play an important role in the pathogenesis of osteoarthritis in dogs.

Evaluación de desenlace: trasplante meniscal versus segunda meniscectomía

Introducción: El incremento de pacientes sintomáticos de rodilla y la osteoartrosis en jóvenes con limitadas posibilidades terapéuticas después de una meniscectomía, genera la búsqueda de alternativas terapéuticas. A pesar que es poco utilizado en Colombia, el trasplante meniscal es una propuesta para el manejo sintomático. Según cifras norteamericanas, se practican entre 700.000 a 1.500.000 artroscopias de rodilla anualmente, el 50% termina en meniscectomía y de este un 40% persisten sintomáticos. Métodos: Estudio de cohorte retrospectivo, con el objetivo de evaluar dolor (Escala Visual Análoga-EVA) y funcionalidad (Escala de Tegner y Lysholm) en los pacientes a quienes se les realizó trasplante meniscal o meniscectomía por segunda vez, entre los años 2007 a 2015. Resultados: A partir de los 6 meses la EVA mostró una tendencia a la mejoría en el grupo de trasplante meniscal, pasando de Moderado a Leve (p: <0.000). La Escala de Tegner y Lysholm cambió de Pobre a Bueno en el grupo de segunda meniscectomía (p= 0.008) y de Bueno a Excelente en el grupo trasplantado (p=0.225). La calificación promedio de la EVA en el grupo de trasplante presentó mejoría (p=<0.000), a diferencia del grupo de segunda meniscectomía (p=0.591). La escala de Tegner y Lysholm, mostró significancia estadística con tendencia a la mejoría en el grupo de segunda meniscectomía. Discusión: Los resultados muestran que con trasplante meniscal hay mejoría del dolor y la funcionalidad versus un segunda meniscectomía. Para fortalecer la evidencia de este tratamiento son necesarios estudios prospectivos complementarios.

Primary Joint Arthroplasty Surgery: Is the Risk of Major Bleeding Higher in Elderly Patients? A Retrospective Cohort Study

Increased risk of bleeding after major orthopedic surgery (MOS) has been widely documented in general population. However, this complication has not been studied in elderly patients. The purpose of this study is to determine whether the risk of major bleeding after MOS is higher in elderly patients, compared with those operated at a younger age. Methods: This retrospective cohort study included total hip and total knee arthroplasty patients operated during 5 consecutive years. The main outcome was the occurrence of major bleeding. Patients with other causes of bleeding were excluded. Relative risks (RRs) and confidence intervals (CIs) were calculated, anda multivariate analysis was performed. Results: A total of 1048 patients were included, 56% of patients were hip arthroplasties. At the time of surgery, 553 (53%) patients were older than 70 years. Patients aged >70 years showed an increased risk of major bleeding (RR: 2.42 [95% CI: 1.54-3.81]). For hip arthroplasty, the RR of bleeding was 2.61 (95%CI: 1.50-4.53) and 2.25 (95% CI: 1.03-4.94) for knee arthroplasty. After multivariate analysis, age was found to be independently associated with higher risk of major bleeding. Conclusion: According to European Medicines Agency criteria, patients aged 70 years are at a higher risk of major bleeding after MOS, result of a higher frequency of blood transfusions in this group of patients. Standardized protocols for blood transfusion in these patients are still required.

Aragonite-based scaffold for the treatment of knee osteochondral defects: results of a prospective multi-center trial at 2 years' follow-up

PURPOSE: To evaluate the clinical and MRI outcomes after the implantation of a nanostructured cell free aragonite-based scaffold in patients affected by knee chondral and osteochondral lesions. METHODS: 126 patients (94 men, 32 women; age 32.7±8.8 years) were included according to the following criteria: grade III or IV chondra/osteochondral lesions in the femoral condyles or throclea; 2) no limb axial deviation (i.e. varus or valgus knee > 5°); 3) no signs of knee instability; 4) no concurrent tibial or patellar chondral/osteochondral defects. All patients were treated by arthrotomic implantation of an aragonite based-scaffold by a press-fit technique. Patients were prospectively evaluated by IKDC, Tegner, Lysholm and KOOS scores preoperatively and then at 6, 12, 18 and 24-months follow-up. MRI was also performed to evaluate the amount of defect filling by regenerated cartilage. Failures were defined as the need for re-intervention in the index knee within the follow-up period. RESULTS: Average defect size was 2±1.3 cm2 and in most cases a single scaffold was used. A significant improvement in each clinical score was recorded from basal level to 24 months’ follow-up. In particular, the IKDC subjective score increased from 42.14±16 to 70.94±24.69 and the Tegner score improved from 2.95±1.90 to 4.82±1.85 (p<0.0005). Lysholm score and all the subscales of KOOS showed a similar trend over time. Age of the patient at implantation, size of the defect and BMI were correlated with lower clinical outcome. The presence of OA didn’t influence the clinical results. MRI evaluation showed a significant increase in defect filling over time, with the highest value reached at 24 months. Failures occurred in eleven patients (8.7%). CONCLUSION: The aragonite-based biomimetic osteochondral scaffold proved to be safe, and encouraging clinical and radiographic outcomes were documented up to 2 years’ follow-up.