Tissue engineering the annulus fibrosus (AF) for use in a functional intervertebral disc replacement is a promising alternative to current treatments of degenerative disc disease. Polycarbonate urethane (PU) scaffolds have demonstrated the ability to support AF cell attachment and matrix synthesis and are suitable for tissue engineering the AF. The present study investigates the effects of the physical and biochemical environment on AF cells grown on aligned nanofibrous PU scaffolds. First, the effect of dynamic spinner flask culture and fibronectin pre-coating on tissue formation was analyzed and then the role of scaffold fibre tension on annulus fibrosus cells was examined using a tailored culture system. The results of these studies demonstrated that AF cells are sensitive to differences in biochemical cues at the scaffold surface and their physical environment and respond by altering their cellular responses and, potentially by manipulating their microenvironments, including the physical characteristics of the PU-ADO scaffolds.

Degenerative disc disease is a common ailment with enormous medical, psychosocial and economic ramifications. This study was designed to investigate the utility of a thiol-modified hyaluronan(TMHA) and elastin-like polypeptide(EP) composite material as a potential tissue engineering scaffold to reconstitute the nucleus pulposus in early degenerative disc disease. TMHA and EP were combined in various concentrations and cross-linked using poly(ethylene glycol)diacrylate. Resulting materials were evaluated biomechanically and biologically. Confined compression testing revealed that the addition of EP to TMHA-based gels resulted in a stiffer construct, but remained an order of magnitude less stiff than native nucleus. The in vitro cell culture experiments with human intervertebral disc cells demonstrated 70% cell viability at three weeks with apparent maintenance of phenotype. The addition of EP did not have a significant biologic effect. An in vivo pilot study demonstrated biocompatibility of the TMHA-based hydrogels; additional power is required to adequately assess treatment effect.

Tissue engineering the annulus fibrosus (AF) for use in a functional intervertebral disc replacement is a promising alternative to current treatments of degenerative disc disease. Polycarbonate urethane (PU) scaffolds have demonstrated the ability to support AF cell attachment and matrix synthesis and are suitable for tissue engineering the AF. The present study investigates the effects of the physical and biochemical environment on AF cells grown on aligned nanofibrous PU scaffolds. First, the effect of dynamic spinner flask culture and fibronectin pre-coating on tissue formation was analyzed and then the role of scaffold fibre tension on annulus fibrosus cells was examined using a tailored culture system. The results of these studies demonstrated that AF cells are sensitive to differences in biochemical cues at the scaffold surface and their physical environment and respond by altering their cellular responses and, potentially by manipulating their microenvironments, including the physical characteristics of the PU-ADO scaffolds.

Der Vortrag behandelt die praktische Umsetzung einer Rast in Rast Kurvenscheibensynthese (Übertragungsfunktion: modifizierte Sinoide) bis zum Ableiten einer ersten Grundform der Kurvenscheibe. Aufgezeigt werden dabei die notwendigen Schritte zur Parametrisierung der Eingabedaten wie Kurvenscheiben- und Übertragungswinkel sowie das spätere Ausleiten einer Spurkurve (Bewegungsaufzeichnung des Kontaktpunktes Kurvenscheibe/Koppel) in das Modell der Kurvenscheibe. Die folgenden notwendigen Optimierungsschritte zur Reduzierung des Krafteingriffswinkels, des Normalkraftverlaufs und der Kurvenscheiben - Mittelpunktslage werden theoretisch behandelt. Das Umsetzen der Optimierung könnte mit Hilfe des Behavioral Modeling Extension - Moduls aus Creo Elements/Pro erfolgen.

Psychosocial factors have been advanced as an explanation for the development of chronic disability in 20 to 30% of patients treated by lumbar disc surgery. Aims: The overall aim of this thesis was to study the role of psychosocial factors in patients undergoing first-time lumbar disc surgery in relation to the outcome of both surgery and subsequent physiotherapy. Methods: Sixty-nine patients with lumbar disc herniation undergoing first-time disc surgery participated in the studies; in addition, Study I included 162 knee patients for comparison. Psychosocial factors were assessed preoperatively, as was the activation of the physiological stress response system. Pain, disabil-ity and quality of life were assessed before, and 3 and 12 months after surgery. Coping and kinesiophobia were analysed before and one year after surgery. The results of two different postoperative training programmes were compared. Results: There were no differences between disc and knee patients regarding the presence of psychosocial stress factors preoperatively (Study I). Disc patients with low diurnal cortisol variability had lower physical function, perceived fewer possibilities to influence their pain and were more prone to catastrophise than patients with high diurnal cortisol variability (Study II). The results of clinic-based physiotherapy and home training did not differ regarding postoperative disability and pain 3 months after surgery. The home-based group had less pain and higher quality of life in comparison to the clinic-based group 12 months after surgery (Study III). Patients’ expectations of returning to work could best predict pain, disability, quality of life and sick leave one year after surgery (Study IV). Psychosocial factors were only weakly asso-ciated to pain, disability, quality of life and sick leave preoperatively. However, these associations were stronger in patients with residual pain one year after surgery. Conclusion: Psychosocial factors and, in particular, patients’ expectations regarding outcome are associated with the results of lumbar disc surgery. Assessing psychosocial factors preoperatively and developing an active home training programme after surgery could create options leading to better results for these patients.

During braking, both the disc and pads in disc brakes are worn. Since disc brakes are not sealed,some of the wear particles generated can become airborne. Several studies have found anassociation between adverse health effects and the concentration of particles in the atmosphere,so it is of interest to improve our knowledge of the airborne wear particles generated by discbrakes. This thesis deals with experimental and computational methods focusing on airborne wearparticles from disc brakes. The eight appended papers discuss the possibility to both measure andnumerically determine the concentration and size distribution of airborne wear particles thatoriginate from the pad-to-disc contact. The objective is to increase the scientific knowledge ofairborne wear particles generated from disc brakes. Papers A, B and C describe tests of disc brake materials conducted in a modified pin-on-discmachine. The results show that the test set-up can be used to measure and rank disc brakematerials with respect to the concentration of airborne particles generated. Ultrafine (nanosized),fine and coarse airborne wear particles that contain metals such as iron, copper and tin werefound. Papers D and E describe a novel disc brake assembly test stand and tests of disc brake materialsconducted in it. The results show that the test set-up can be used to measure the concentrationand size distribution of airborne wear particles generated from disc brake materials. The resultsalso indicate an ability to rank different pad/disc combinations with respect to the concentrationof airborne wear particles. Furthermore, the results suggest that this test stand can be used tostudy rust layer removal from the disc and that airborne particles are generated even at low brakepressures, such as used to remove dirt from the disc. Paper F compares measurements made in passenger car field tests with measurements made in adisc brake assembly test stand and in a pin-on-disc machine. A promising correlation between thethree different test methods is found. Paper G presents and discusses a simulation methodology that numerically determines theconcentration and size distribution of airborne wear particles generated from the pad-to-disccontact in disc brakes by using general-purpose finite element software. Paper H discusses a cellular automaton model that describes the microscopic contact situationbetween the pad and disc in disc brakes. This model is used to numerically determine the amountof wear that leaves the contact. The results correlate qualitatively with experimental observationsfound in the literature. / QC 20110317

Low back pain is an ailment that affects a significant portion of the community. However, due to the complexity of the spine, which is a series of interconnected joints, and the loading conditions applied to these joints the causes for back pain are not well understood. Investigations of damage or failure of the spinal structures from a mechanical viewpoint may be viewed as a way of providing valuable information for the causes of back pain. Low back pain is commonly associated with injury to, or degeneration of, the intervertebral discs and involves the presence of tears or lesions in the anular disc material. The aim of the study presented in this thesis was to investigate the biomechanical effect of anular lesions on disc function using a finite element model of the L4/5 lumbar intervertebral disc. The intervertebral disc consists of three main components - the anulus fibrosus, the nucleus pulposus and the cartilaginous endplates. The anulus fibrosus is comprised of collagen fibres embedded in a ground substance while the nucleus is a gelatinous material. The components of the intervertebral disc were represented in the model together with the longitudinal ligaments that are attached to the anterior and posterior surface of the disc. All other bony and ligamentous structures were simulated through the loading and boundary conditions. A high level of both geometric and material accuracy was required to produce a physically realistic finite element model. The geometry of the model was derived from images of cadaveric human discs and published data on the in vivo configuration of the L4/5 disc. Material properties for the components were extracted from the existing literature. The anulus ground substance was represented as a Mooney-Rivlin hyperelastic material, the nucleus pulposus was modelled as a hydrostatic fluid in the healthy disc models and the cartilaginous endplates, collagen fibres and longitudinal ligaments were represented as linear elastic materials. A preliminary model was developed to assess the accuracy of the geometry and material properties of the disc components. It was found that the material parameters defined for the anulus ground substance did not accurately describe the nonlinear shear behaviour of the tissue. Accurate representation this nonlinear behaviour was thought to be important in ensuring the deformations observed in the anulus fibrosus of the finite element model were correct. There was no information found in the literature on the mechanical properties of the anulus ground substance. Experimentation was, therefore, carried out on specimens of sheep anulus fibrosus in order to quantify the mechanical response of the ground substance. Two testing protocols were employed. The first series of tests were undertaken to provide information on the strain required to initiate permanent damage in the ground substance. The second series of tests resulted in the acquisition of data on the mechanical response of the tissue to repeated loading. The results of the experimentation carried out to determine the strain necessary to initiate permanent damage suggested that during daily loading some derangement might be caused in the anulus ground substance. The results for the mechanical response of the tissue were used to determine hyperelastic constants which were incorporated in the finite element model. A second order Polynomial and a third order Ogden strain energy equation were used to define the anulus ground substance. Both these strain energy equations incorporated the nonlinear mechanical response of the tissue during shear loading conditions. Using these geometric data and material properties a finite element model of a representative L4/5 intervertebral disc was developed. When the measured material parameters for the anulus ground substance were implemented in the finite element model, large deformations were observed in the anulus fibrosus and excessive nucleus pressures were found. This suggested that the material parameters defining the anulus ground substance were overly compliant and in turn, implied the possibility that the stiffness of the sheep anulus ground substance was lower than the stiffness of the human tissue. Even so, the mechanical properties of the sheep joints had been shown to be similar to those of the human joint and it was concluded that the results of analyses using these parameters would provide valuable qualitative information on the disc mechanics. To represent the degeneration of the anulus fibrosus, the models included simulations of anular lesions - rim, radial and circumferential lesions. Degeneration of the nucleus may be characterised by a significant reduction in the hydrostatic nucleus pressure and a loss of hydration. This was simulated by removal of the hydrostatic nucleus pressure. Analyses were carried out using rotational loading conditions that were comparable to the ranges of motion observed physiologically. The results of these analyses showed that the removal of the hydrostatic nucleus pressure from an otherwise healthy disc resulted in a significant reduction in the stiffness of the disc. This indicated that when the nucleus pulposus is extremely degenerate, it offers no resistance to the deformation of the anulus and the mechanics of the disc are significantly changed. Specifically, the resistance to rotation offered by the intervertebral disc is reduced, which may affect the stability of the joint. When anular lesions were simulated in the finite element model they caused minimal changes in the peak moments resisted by the disc under rotational loading. This suggested that the removal of the nucleus pressure had a greater effect on the mechanics of the disc than the simulation of anular lesions. The results of the finite element model reproduced trends observed in both the healthy and degenerate intervertebral disc in terms of variations in nucleus pressure with loading conditions, axial displacement of the superior surface and bulge of the peripheral anulus. It was hypothesised that the reduced rotational stiffness of the degenerate disc may result in overload of the surrounding innervated osseoligamentous anatomy which may in turn cause back pain. Similarly back pain may result from the abnormal deformation of the innervated peripheral anulus in the vicinity of anular lesions. Furthermore, it was hypothesised that biochemical changes may result in the degeneration of the nucleus, which in turn may cause excessive strains in the anulus ground substance and lead to the initiation of permanent damage in the form of anular lesions. With further refinement of the components of the model and the methods used to define the anular lesions it was considered that this model would provide a powerful analysis tool for the investigation of the mechanics of intervertebral discs with and without significant degeneration.

Low back pain is a common cause of disability and work inability, often associated with intervertebral disc degeneration. The current understanding of disc degeneration is limited and none of the available treatments is entirely effective. The work described herein investigates potential strategies for the biological herapeutic restoration of disc degeneration. Firstly, an in vitro study to investigate the effects of BMP-7 on human discal cellular viability was performed. Cultured cells were treated with TNF-a or H202 to induce apoptosis, resulting in the down regulation of extracellular matrix proteins, decreased cell viability, morphological changes and activation of caspase-3; however, addition of BMP-7 alone prevented the observed effects, demonstrating the ability of BMP-7 to prevent apoptosis of human disc cells in vitro. Secondly, the differentiation potential of stem cells towards disc-like cells was studied. Rodent mesenchymal stem cells (rMSCs) were cultured alone or co-cultured with rat disc tissue. Differentiation potential of rMSCs was evaluated by mRNA and protein expression, cellular function and morphological studies. The co-culture conditions led to the expression of chondrocytic markers in rMSCs, whereas rMSCs cultured alone did not express the chondrocytic markers. Cellular contact between the co-cultured rMSCs and the discal tissue were observed. This study demonstrated that rMSCs can differentiate into functional disc-like cells in a tissue influenced co-culture environment. Finally, the survival and differentiation of CD34+ or CD34?? bone marrow (hBM) cells, in an intra-discal xenogeneic transplantation rat model was investigated. Human CD34+ or CD34?? cells were isolated, fluorescent-labelled and injected into rat coccygeal discs. The survival of transplanted cells was confirmed by fluorescent positive cells as well as a human nuclear specific marker. Interestingly, CD34?? cells survived until day 42 in the injected discs, and differentiated into cells ex:pressing a chondrocytic phenotype. In contrast, CD34+ cells could not be detected by day 21. This data suggests that transplanted hBM CD34?? cells, in contrast to CD34+ cells, were able to survive and differentiate within the intervertebral disc. Together, the results of these studies can both encourage and contribute to the basis of potential biological therapies in the restoration of intervertebral disc degeneration.

Process intensification tools, such as the capillary reactor, offer several benefits to the chemical process industries due to the well-defined high specific interfacial area available for heat and mass transfer, which increases the transfer rates, and due to low inventories, they also enhance the safety of the process. This has provided motivation to investigate three such tools, namely the capillary microreactor, spinning disc and rotating tube reactors, in this study. / The gas-liquid slug flow capillary microreactor intensifies reactor performance through internal circulation caused by the shear between the continuous phase/wall surface and the slug axis, which enhances the diffusivity and consequently increases the reaction rates. However, integrating the complex hydrodynamics of this reactor with its chemical kinetics is a mathematically challenging task. Therefore, in this study, a simple-to-complex approach, using a set of state-of-the-art computational fluid dynamic tools, has been used. Firstly, simulations were performed without any chemical reaction to ascertain the extent of slug flow regime. The model also clearly captured the slug flow generation mechanism which can be used to structurally optimize the angle of entry in these reactors. Finally, the hydrodynamic model was also capable of estimating the pressure drop and slug lengths. After successfully simulating the hydrodynamics of the system, a reaction model was incorporated to study the chemical reaction kinetics. The results were compared with the published experimental work and were found to be in good agreement. / The spinning disc reactor utilizes the centrifugal and shear forces to generate thin liquid films characterized with intense interfering waves. This enables a very high heat transfer coefficients to be realized between the disc and liquid, as well as very high mass transfer between the liquid and the bulk gas phase. The waves formed also produce an intense local mixing with very little back mixing. This makes a spinning disc reactor an ideal contactor for multiphase processes. The focus of this study has been to elucidate the hydrodynamic behaviour of the liquid film flow over the horizontal spinning disc. Investigations were also performed to elaborate the local and overall hydrodynamic characteristics of a fully developed spinning disc reactor. Simulation results showed a continuous linear liquid film on the horizontal spinning disc and intense mixing performance in the annulus of the reactor around the disc surface. Finally, the film thickness data from the simulations were compared with the limited amount of data available for this novel process. / Rotating tube reactor also uses centrifugal forces to generate the liquid film and a high degree of mixing along with an improved control over the reactant retention times. In this work we have conducted a CFD analysis to understand the hydrodynamics of this new technology for future developments.

Thesis (PhD)--Macquarie University, Division of Humanities, Department of Contemporary Music Studies, 2007. / Bibliography: p. 291-313.