Knee cartilage loss in symptomatic knee osteoarthritis over 4.5 years

The objective of this study was to describe the rate of change in knee cartilage volume over 4.5 years in subjects with symptomatic knee osteoarthritis (OA) and to determine factors associated with cartilage loss. One hundred and five subjects were eligible for this longitudinal study. Subjects' tibial cartilage volume was assessed by magnetic resonance imaging (MRI) at baseline, at 2 years and at 4.5 years. Of 105 subjects, 78 (74%) completed the study. The annual percentage losses of medial and lateral tibial cartilage over 4.5 years were 3.7 ± 4.7% (mean ± SD; 95% confidence interval 2.7 to 4.8%) and 4.4 ± 4.7% (mean ± SD; 95% confidence interval 3.4 to 5.5%), respectively. Cartilage volume in each individual seemed to track over the study period, relative to other study participants. After multivariate adjustment, annual medial tibial cartilage loss was predicted by lesser severity of baseline knee pain but was independent of age, body mass index and structural factors. No factors specified a priori were associated with lateral cartilage volume rates of change. Tibial cartilage declines at an average rate of 4% per year in subjects with symptomatic knee OA. There was evidence to support the concept that tracking occurs in OA. This may enable the prediction of cartilage change in an individual. The only significant factor affecting the loss of medial tibial cartilage was baseline knee pain, possibly through altered joint loading

Relationships between image-based and mechanical bone properties with pain in knee osteoarthritis

Pain is the predominant symptom of OA, a debilitating disease marked by changes in cartilage and subchondral bone, but pain pathophysiology is poorly understood. Bone is densely innervated and may be linked to OA-related knee pain. Quantitative computed tomography (QCT) is an in vivo image-based technique with the potential to quantify bone mineral density (BMD) to explore the role of bone in OA-related pain. When coupled with subject-specific finite element (FE) modeling, it may be possible to clarify the mechanical role of bone in OA-related knee pain. The objectives of this study were to assess if: 1) tibial subchondral BMD is associated with OA-related nocturnal knee pain using depth-specific QCT image processing, 2) tibial epiphyseal and metaphyseal BMD is associated with OA-related knee pain using a modified depth-specific CT image processing tool, 3) subchondral cyst characteristics are associated with OA-related knee pain, and 4) FE-derived mechanical outcomes at the proximal tibia are associated with OA-related pain. Lateral focal subchondral BMD was 33% higher in participants with severe nocturnal pain than participants with no nocturnal pain at the 2.5-5mm depth (p=0.028) and 32% higher at 5-10mm from the subchondral surface (p=0.049). At the epiphyseal and metaphyseal depths, higher total pain was associated with lower medial epiphyseal BMD (R2=-0.40, p=0.002), and lower metaphyseal BMD (R2=-0.35, p=0.017). At the lateral region, subchondral cyst number (r=0.55, p<0.001) and cyst number per proximal tibial volume (r=0.52, p<0.001) were both associated with BMD, and lateral cyst number and volume were associated with joint space narrowing (r=0.52 to 0.68, p<0.001) and alignment (r=0.44 to 0.62, p<0.001). In our FE study, principal compressive stress was associated with nocturnal pain at most lateral regions (r=0.33 to 0.50, p<0.05). Principal compressive stress at the lateral region ranged from 47% to 67% higher (p<0.05) in participants with severe nocturnal pain than participants with no pain. This series of studies suggests that pain in patients with knee OA may be associated with BMD throughout various depths at the proximal tibia as well as FE-based bone mechanical outcomes, such as principal compressive stress. These findings suggest previously unexplored associations between OA-related knee pain and BMD or mechanical outcomes, emphasizing that bone may have a mechanical role in OA-related pain pathogenesis

Self-Assembling Peptides for Cartilage Regeneration

Loss of glycosaminoglycans (GAGs) in osteoarthritic (OA) cartilage contributes to a decrease in mechanical properties and function in vitro, and is considered to be a major contributor to disease progression. The aims of this investigation were to test the hypothesis that a combination of self-assembling peptides (SAPs) and chondroitin sulfate (glycosaminoglycan; GAG) would restore the biomechanical properties of GAG depleted porcine condylar cartilage, ideally to a level intrinsic to native porcine condylar cartilage. The SAPs investigated were members of the P11 series which have been designed to spontaneously self-assemble into three-dimensional fibrilar hydrogels, in response to physiological conditions. Initial studies were carried out to determine which of three peptides (P11-4, P11-8 and P11-12) demonstrated high β-sheet percentage, long-woven fibrilar networks and high stiffness; when mixed with chondroitin sulfate at two different GAG molar ratios (1:16 and 1:64) in physiological conditions, using FTIR analysis, transmission electron microscopy and rheology. The β-sheet percentage, dimensions of fibrils and stiffness were dependent upon the peptide, GAG molar ratio and Na2+ salt concentration. P11-4 and P11-8: GAG mixtures had high β-sheet percentage ranging from 50.6-91 % and 81.7-92 %, respectively. Fibril lengths of the P11-4 and P11-8: GAG mixtures were in the range 498- 3518 nm and the elastic shear modulus (G’) ranged from 4,479-10,720 Pa and 7,722-26,854 Pa, respectively. P11-4 and P11-8: GAG mixtures were selected for further investigation. In order to produce a GAG depleted cartilage model, porcine femoral condylar cartilage was subjected to three different methods of GAG depletion (1) coating the surface with chondroitinase ABC (2) injecting chondroitinase ABC into the cartilage (3) washing the condyles in sodium dodecyl sulfate (SDS). GAG depletion was successfully achieved following two 24 hour washes in 0.1 % (w/v) SDS and buffer washes. Histological analysis of safranin O stained sections revealed an absence of GAGs. Quantification of GAGs using the dimethylemethylene blue assay revealed that 75 % of GAGs had been removed. In order to assess the effects of peptide: GAG mixtures on the biomechanical properties of the GAG depleted porcine condylar cartilage a biomechanical test method was developed. A series of indentation tests using different loads, followed by finite element analysis of the data were performed on native and GAG depleted porcine condylar cartilage; to identify a suitable load for detection of a significant difference in the deformation, equilibrium elastic modulus and permeability between the native and GAG depleted porcine condylar cartilages. A load of 0.31 N was identified as the most appropriate. GAG depleted porcine condylar cartilage was injected with P11-4 and P11-8 alone, P11-4 and P11-8 : GAG mixtures at a molar ratio of 1:64 and chondroitin sulfate alone. The average percentage deformation of the medial condylar cartilage samples injected with P11-4 alone and P11-4: GAG mixture was 15.5 % and 8.7 % and for P11-8 alone and P11-8: GAG mixture was 11.4 % and 9.1 % respectively; compared to 6.3 % for the native cartilage and 12.6 % for the GAG depleted cartilage. The average equilibrium elastic modulus of the medial cartilage samples injected with P11-4 alone and P11-4: GAG mixture was 0.16 MPa and 0.43 MPa and for P11-8 alone and P11-8: GAG, 0.23 MPa and 0.35 MPa, respectively; compared to 0.49 MPa for the native cartilage and 0.21 MPa for the GAG depleted cartilage. Statistical analysis (ANOVA) showed that a mixture of P11-4: GAG, but not P11-8: GAG restored both the percentage deformation and equilibrium elastic modulus of the GAG depleted cartilage to levels that were not significantly different to the native cartilage. This study has shown that the use of P11-4 in combination with chondroitin sulfate has future potential for development as a minimally invasive treatment for early stage osteoarthritis

Experimental and numerical characterization of the viscoelastic behaviour of cartilages and soft tissues of the human nose

Dissertação de mestrado integrado em Engenharia BiomédicaThe facial plastic surgery, and particularly the area of rhinoplasty, is undoubtedly a growing up market. Surgical techniques have been evolving to respond to very specific patient desires not only for functional reasons, but also to resolve aesthetic issues. Actually, it is moving plenty of money around the world, being a great scientific and commercial opportunity among researchers. The human nose is composed of three major portions separated by two well-defined regions of transition (K-area and S-area) that are very complicated to deal with in postoperative periods. The viscoelastic behaviour of soft biological tissues, especially that of nasal cartilages and adjacent subcutaneous/fatty tissues, is barely known. There are no studies on the viscoelastic characterization of the mechanical properties of nasal septum (NS), upper lateral cartilages (ULC), and lower lateral cartilages (LLC) in creep and relaxation (basic viscoelasticity features) neither on the determination of frequency- and temperature-dependent properties of these tissues through dynamic mechanical analysis (DMA) in tension and compression. General information on thermal degradations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) is also missing. Therefore, part of this work intends to fill this lack of the literature giving some insights into the cartilage internal composition and architecture, as well as the specificity of the activated mechanisms under constant stress or strain. Furthermore, numerical simulations were performed based on a hyper-viscoelastic mathematical formulation using a home-made open-source finite element (FE) solver (V-Biomech) in order to find a set of basic constitutive parameters that allow to replicate the experimental creep and relaxation behaviours of nasoseptal cartilage specimens from distinct regions of the quadrilateral cartilage (QLC). Thus, a complete standard biphasic poro-hyper-viscoelastic constitutive law was developed and validated. Finite Element Models (FEM) are gaining relevance to analyse soft biological components. As example, numerical simulations of the viscoelastic behaviours of the specimens harvested from anterior part of the QLC were performed to understand which of the constitutive parameters were more sensitive to achieve the best numerical-experimental agreement. The tools to reproduce these simulations in a more complex geometry (the whole nasal structure, with bony and cartilaginous components) were also developed and presented. The work still goes on it.A cirurgia plástica facial, e em particular a área da rinoplastia, é indubitavelmente um mercado em crescimento. As técnicas cirúrgicas têm evoluído no sentido de dar resposta aos desejos mais específicos de cada paciente não só por razões funcionais, mas também para resolução de problemas estéticos. Atualmente, é uma área que movimenta muito dinheiro em todo o mundo, tornando-se numa evidente oportunidade científica e comercial. O nariz humano está dividido em três regiões principais separadas por duas zonas de transição (áreas K e S) que são muito difíceis de manipular em períodos de recuperação pós-cirurgia. O comportamento viscoelástico de tecidos moles, especialmente o das cartilagens nasais e dos tecidos subcutâneo/adiposo adjacentes, é pouco conhecido. Atualmente, não existem estudos sobre a caracterização de propriedades mecânicas da cartilagem septal nem das cartilagens laterais superiores ou inferiores em fluência e relaxação (características de comportamentos viscoelásticos). A determinação de propriedades mecânicas em função da frequência de oscilação e da temperatura para estes mesmos materiais através de uma análise de DMA em tensão e compressão, assim como informações gerais sobre fenómenos de degradação térmica por DSC e TGA, também não são reportados. Assim sendo, parte desta dissertação pretende preencher esta lacuna da literatura, contribuindo para a compreensão da composição e arquitetura internas da cartilagem e da especificidade dos mecanismos ativados sob influência de uma tensão ou deformação constantes. Além disso, foram levadas a cabo simulações numéricas baseadas numa formulação matemática de híper-viscoelasticidade num software de elementos finitos desenvolvido na Instituição (V-Biomech) e foram encontrados os valores dos parâmetros que permitem replicar o comportamento experimental de fluência e relaxação de cartilagens de diferentes regiões do septo nasal. Assim, uma lei constitutiva que agrega conceitos de híper-elasticidade, viscoelasticidade e permeabilidade, acoplando o distinto comportamento de materiais sólidos e fluidos, foi desenvolvida e validada. Além das simulações do comportamento viscoelástico das amostras colhidas a partir da região anterior do septo, um conjunto de outras ferramentas para aplicação dos mesmos conceitos numa geometria mais complexa foi também desenvolvido e apresentado. Um trabalho que ainda continua

Tribological testing of potential hemiarthroplasty materials using a custom-designed multi-directional reciprocating rig

The material selection plays a major role in the design of a patellofemoral joint (PFJ) replacement due to the reported damage of the femoral condyles in deep knee flexion using ultra-high molecular weight polyethylene for the patellar components. The use of softer materials such as PCU and PVA/PVP may induce fluid film lubrication and thus reduce the risk of cartilage damage. This research aims to investigate in-vitro tribological performance of the articulation of cartilage-on-PCU (Bionate® I 80A and Bionate® II 80A) and cartilage-on-PVA/PVP (different concentrations and PVA to PVP fractions) using a custom-designed multi-directional pin-on-plate rig. PVA/PVP showed low COF values (between 0.12±0.01 and 0.14±0.02) which were closer to the cartilage-on-cartilage articulation (0.03±0.01) compared to PCUs (0.41±0.02 for Bionate® II 80A and 0.50±0.02 for Bionate® I 80A). However, these PVA/PVP hydrogels were worn massively after 15 h articulation against the condyles. On the other hand, the counter-face condyles of PCUs were severely damaged, similar to the damage observed in the cartilage-on-stainless steel articulation. Among the PCUs, Bionate® II 80A showed superior tribological performance without depending on the lubricant and surface roughness parameters. When a migrating cartilage contact was achieved by articulating PCU pins on cartilage plates, PCUs revealed similar COF values (0.04±0.01) to the cartilage-on-cartilage articulation. This work has shown that PVA/PVP hydrogels require further development to enhance their wear resistance if they are to be used as part of a joint replacement. However, they have low COF against articular cartilage and so are attractive possibilities for the future. The tested PCU grades have shown PCUs (especially Bionate® II 80A) can work with acceptably low COF under the right articulating conditions and that they have low wear in those tests. Therefore, the work in this thesis supports the further development of patellofemoral joint prostheses which include PCU components.Open Acces

Effect of Mandibular Displacement on Condylar Cartilage Remodelling In Sprague Dawley Rats: A Micro-Structural Analysis

Three dimensional (3D) imaging of cartilage has always been difficult due to the inherent intermediary density between soft tissue and hard tissue in X-rays images, particularly in Micro Computer Tomography (MicroCT). Recent advances in imaging techniques have allowed for the enhancement of cartilage visualization for MicroCT use. Aim: The objective of this study was to provide a new insight in understanding changes in condylar cartilage, determined qualitatively and quantitatively, with normal growth and after the placement of an appliance over a 4 week period. Materials and Methods: Seventy Sprague Dawley rats (five weeks old) were divided into either a control group or an experimental group in which bite ramps were placed on the lower incisors at Day 0. Animals were sacrificed at Days 0, 7, 21 and 28. Right hemisections were then taken and stained with gadolinium chloride for six days before being scanned via a MicroCT unit. Condylar cartilage was digitally extracted from the scans and volumetric measurements were carried out and assessed quantitatively. Three dimensional images of the condyles were also assessed qualitatively for morphological changes between appliances and over the experimental duration. An intra-individual method error study was also carried out. Results Conformational changes were noted in the shape of the condyle between appliance groups and over the treatment duration. Qualitative assessment of the condyles demonstrated a reduction in size over time in all groups with a change in shape of the condylar heads. Anterior displacement of the mandible resulted in significant remodeling and distinctive shape changes that differ from both control and posterior displacement groups. Quantitative analysis demonstrated differences between control and appliance groups in regards to Total volume of the whole condylar head, Total cartilage volume, Total volume of the posterior hemisection of the condylar head and Posterior cartilage volume. The Method error study demonstrated the high reproducibility of results with a coefficient of variation of 5-13%. Discussion This study demonstrated a new method for analysing changes in the condylar head following orthopaedic intervention. Assessment of these changes in the condylar head can now be depicted via a three dimensional, non-destructive method. Hence, growth changes of the condylar head can now be evaluated in its totality compared to traditional methods of assessing cartilage changes sectionally via histological slices. Therefore, this provides a new avenue for improving our understanding in the changes that occur in the condylar head with growth and after intervention. It may also promote further investigations into the effects of systemic drugs on normal growth and manipulation of this important site of growth

Visualisation of Articular Cartilage Microstructure

This thesis developed image processing techniques enabling the detection and segregation of biological three dimensional images into its component features based upon shape and relative size of the features detected. The work used articular cartilage images and separated fibrous components from the cells and background noise. Measurement of individual components and their recombination into a composite image are possible. Developed software was used to analyse the development of hyaline cartilage in developing sheep embryos

Effect of Mandibular Displacement on Condylar Cartilage Remodelling In Sprague Dawley Rats: A Micro-Structural Analysis

Three dimensional (3D) imaging of cartilage has always been difficult due to the inherent intermediary density between soft tissue and hard tissue in X-rays images, particularly in Micro Computer Tomography (MicroCT). Recent advances in imaging techniques have allowed for the enhancement of cartilage visualization for MicroCT use. Aim: The objective of this study was to provide a new insight in understanding changes in condylar cartilage, determined qualitatively and quantitatively, with normal growth and after the placement of an appliance over a 4 week period. Materials and Methods: Seventy Sprague Dawley rats (five weeks old) were divided into either a control group or an experimental group in which bite ramps were placed on the lower incisors at Day 0. Animals were sacrificed at Days 0, 7, 21 and 28. Right hemisections were then taken and stained with gadolinium chloride for six days before being scanned via a MicroCT unit. Condylar cartilage was digitally extracted from the scans and volumetric measurements were carried out and assessed quantitatively. Three dimensional images of the condyles were also assessed qualitatively for morphological changes between appliances and over the experimental duration. An intra-individual method error study was also carried out. Results Conformational changes were noted in the shape of the condyle between appliance groups and over the treatment duration. Qualitative assessment of the condyles demonstrated a reduction in size over time in all groups with a change in shape of the condylar heads. Anterior displacement of the mandible resulted in significant remodeling and distinctive shape changes that differ from both control and posterior displacement groups. Quantitative analysis demonstrated differences between control and appliance groups in regards to Total volume of the whole condylar head, Total cartilage volume, Total volume of the posterior hemisection of the condylar head and Posterior cartilage volume. The Method error study demonstrated the high reproducibility of results with a coefficient of variation of 5-13%. Discussion This study demonstrated a new method for analysing changes in the condylar head following orthopaedic intervention. Assessment of these changes in the condylar head can now be depicted via a three dimensional, non-destructive method. Hence, growth changes of the condylar head can now be evaluated in its totality compared to traditional methods of assessing cartilage changes sectionally via histological slices. Therefore, this provides a new avenue for improving our understanding in the changes that occur in the condylar head with growth and after intervention. It may also promote further investigations into the effects of systemic drugs on normal growth and manipulation of this important site of growth