Development and experimental validation of a dynamic numerical model for human articular cartilage.

The purpose of this study was to create a preliminary set of experimentally validated Finite Element Analysis (FEA) models, in order to predict the dynamic mechanical behaviour of human articular cartilage (AC). Current models consider static loading with limited independent experimental validation, while the models for this study assess dynamic loading of AC, with direct comparison and validation to physical testing. Three different FEA models of AC were constructed, which considered both linear elastic and hyperelastic models; Neo-Hookean and Ogden. Models were validated using the data collected from compression testing of human femoral heads across 0-1.7 MPa (quasi-static tests and dynamic mechanical analysis). The linear elastic model was inadequate, with a 10-fold over prediction of the displacement dynamic amplitude. The Neo-Hookean model accurately predicted the dynamic amplitude but failed to predict the initial compression of the cartilage, with a 10 times overprediction. The Ogden model provided the best results, with both the initial compression lying within one standard deviation of that observed in the validation data set, and the dynamic amplitude of the same order of magnitude. In conclusion, this study has found that the fast dynamic response of human AC is best represented by a third order Ogden model.

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel.

This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear-confinement to form microparticulate suspensions, through a bottom-up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles "grown" in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non-gelled polymer within the continuous phase, creating an amorphous-like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid-like behaviors at rest with defined yielding; likely through intrinsic particle-particle and particle-polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click-chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9. These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics.

Dynamic viscoelastic characterisation of human osteochondral tissue: understanding the effect of the cartilage-bone interface.

BACKGROUND: Despite it being known that subchondral bone affects the viscoelasticity of cartilage, there has been little research into the mechanical properties of osteochondral tissue as a whole system. This study aims to unearth new knowledge concerning the dynamic behaviour of human subchondral bone and how energy is transferred through the cartilage-bone interface. METHODS: Dynamic mechanical analysis was used to determine the frequency-dependent (1-90 Hz) viscoelastic properties of the osteochondral unit (cartilage-bone system) as well as isolated cartilage and bone specimens extracted from human femoral heads obtained from patients undergoing total hip replacement surgery, with a mean age of 78 years (N = 5, n = 22). Bone mineral density (BMD) was also determined for samples using micro-computed tomography as a marker of tissue health. RESULTS: Cartilage storage and loss moduli along with bone storage modulus were found to increase logarithmically (p < 0.05) with frequency. The mean cartilage storage modulus was 34.4 ± 3.35 MPa and loss modulus was 6.17 ± 0.48 MPa (mean ± standard deviation). In contrast, bone loss modulus decreased logarithmically between 1 and 90 Hz (p < 0.05). The storage stiffness of the cartilage-bone-core was found to be frequency-dependent with a mean value of 1016 ± 54.0 N.mm- 1, while the loss stiffness was determined to be frequency-independent at 78.84 ± 2.48 N.mm- 1. Notably, a statistically significant (p < 0.05) linear correlation was found between the total energy dissipated from the isolated cartilage specimens, and the BMD of the isolated bone specimens at all frequencies except at 90 Hz (p = 0.09). CONCLUSIONS: The viscoelastic properties of the cartilage-bone core were significantly different to the tissues in isolation (p < 0.05). Results from this study demonstrate that the functionality of these tissues arises because they operate as a unit. This is evidenced through the link between cartilage energy dissipated and bone BMD. The results may provide insights into the functionality of the osteochondral unit, which may offer further understanding of disease progression, such as osteoarthritis (OA). Furthermore, the results emphasise the importance of studying human tissue, as bovine models do not always display the same trends.

Investigating the potential of Zernike polynomials to characterise spatial distribution of macular pigment.

It has been postulated that particular patterns of macular pigment (MP) distribution may be associated with the risk for eye diseases such as age-related macular degeneration (AMD). This work investigates the potential of Zernike polynomials (ZP) to characterise the level and distribution of MP, and their suitability as a representation for analysis of the effects of age and AMD on MP patterns. As the case study, MP distribution maps computed using an experimental method based on fundus reflectance (MRIA) were obtained for ninety volunteers representing three groups: under-fifty without AMD, fifty and over without AMD, and fifty and over with AMD. ZP with 105 coefficients were fitted to the maps using least-squares optimisation and found to represent MP maps accurately (RMSE<10-1). One-way MANOVA analysis carried out on ZP representations showed that the three subject groups have significantly different means (Wilk's Lambda 0.125, p<0.0001). Linear discriminant analysis with leave-one-out scheme resulted in accuracy, sensitivity and specificity of classification according to, respectively, disease status regardless of age (81% all); disease status in the age-matched groups (87%, 88%, 86%); age irrespective of disease status (81%, 83%, 73%); and age for subjects without AMD (83%, 88%, 80%). Mean MP distributions computed from ZP coefficients for the three groups showed more elevated and more peaked MP for the healthy under-fifty group; more irregular and more elevated peripheral levels in over-fifty AMD group than in over-fifty non-AMD group; and moderate radial asymmetry in non-AMD over-50 group. The results suggest that ZP coefficients are capable of accurately representing MP in a way that captures certain spatial patterns of its distribution. Using the ZP representation MP maps could be classified according to both age and disease status with accuracy significantly greater than chance, with peak elevation, pattern irregularity and radial asymmetry identified as important features.