Design and synthesis of proteoglycan analogues for tissue repair and regeneration

This thesis is concerned with the design and synthesis of a novel, injectable proteoglycan analogue for tissue repair. This is of particular relevance to the restoration of disc height to a degraded nucleus pulposus of the intervertebral disc. The focus is on the use of sulfonate monomers as proteoglycan analogues, in particular sodium 2-acrylamido-2-methylpropane sulfonic acid and the potassium salt of 3-sulfopropyl acrylate. For most biomedical applications, synthetic hydrogels need to show dimensional stability to changes in pH, osmolarity, and temperature. This is readily achieved by neutral structures however ionic sulfonate containing hydrogels are responsive to environmental change which renders them difficult to manage in most tissue replacement applications. In this case osmotic responsiveness rather than stability is desirable. Therefore sulfonate based materials possess advantageous properties. This is a result of the sulfonate becoming an ideal surrogate for the sulfate group present within the structure of natural proteoglycans. This thesis reports polymerisation studies based on the production of a redox initiated copolymer system capable of polymerising in situ within a timescale of circa. 5-7 minutes. The rheological properties, osmotic drive, and residual monomer content of successful compositions is analysed. Properties are adapted to mimic those of the target natural tissue. The adaptation of the material for use as an injectable intra-ocular lens, with hyaluronic acid as an interpenetrate is reported. The synthesis of a radiopaque macromer to allow visibility of the repair system once in situ is investigated and discussed. The results presented in this thesis describe a suitable proteoglycan tissue analogue which is injectable, biomimetic, osmotically responsive and mechanically stable in its desired application.

Computer simulation of form-roll design

Changes in modern structural design have created a demand for products which are light but possess high strength. The objective is a reduction in fuel consumption and weight of materials to satisfy both economic and environmental criteria. Cold roll forming has the potential to fulfil this requirement. The bending process is controlled by the shape of the profile machined on the periphery of the rolls. A CNC lathe can machine complicated profiles to a high standard of precision, but the expertise of a numerical control programmer is required. A computer program was developed during this project, using the expert system concept, to calculate tool paths and consequently to expedite the procurement of the machine control tapes whilst removing the need for a skilled programmer. Codifying the expertise of a human and the encapsulation of knowledge within a computer memory, destroys the dependency on highly trained people whose services can be costly, inconsistent and unreliable. A successful cold roll forming operation, where the product is geometrically correct and free from visual defects, is not easy to attain. The geometry of the sheet after travelling through the rolling mill depends on the residual strains generated by the elastic-plastic deformation. Accurate evaluation of the residual strains can provide the basis for predicting the geometry of the section. A study of geometric and material non-linearity, yield criteria, material hardening and stress-strain relationships was undertaken in this research project. The finite element method was chosen to provide a mathematical model of the bending process and, to ensure an efficient manipulation of the large stiffness matrices, the frontal solution was applied. A series of experimental investigations provided data to compare with corresponding values obtained from the theoretical modelling. A computer simulation, capable of predicting that a design will be satisfactory prior to the manufacture of the rolls, would allow effort to be concentrated into devising an optimum design where costs are minimised.

Lubrication efficiency and die design in wire drawing

With the competitive challenge facing business today, the need to keep cost down and quality up is a matter of survival. One way in which wire manufacturers can meet this challenge is to possess a thorough understanding of deformation, friction and lubrication during the wire drawing process, and therefore to make good decisions regarding the selection and application of lubricants as well as the die design. Friction, lubrication and die design during wire drawing thus become the subject of this study. Although theoretical and experimental investigations have been being carried out ever since the establishment of wire drawing technology, many problems remain unsolved. It is therefore necessary to conduct further research on traditional and fundamental subjects such as the mechanics of deformation, friction, lubrication and die design in wire drawing. Drawing experiments were carried out on an existing bull-block under different cross-sectional area reductions, different speeds and different lubricants. The instrumentation to measure drawing load and drawing speed was set up and connected to the wire drawing machine, together with a data acquisition system. A die box connected to the existing die holder for using dry soap lubricant was designed and tested. The experimental results in terms of drawing stress vs percentage area reduction curves under different drawing conditions were analysed and compared. The effects on drawing stress of friction, lubrication, drawing speed and pressure die nozzle are discussed. In order to determine the flow stress of the material during deformation, tensile tests were performed on an Instron universal test machine, using the wires drawn under different area reductions. A polynomial function is used to correlate the flow stress of the material with the plastic strain, on which a general computer program has been written to find out the coefficients of the stress-strain function. The residual lubricant film on the steel wire after drawing was examined both radially and longitudinally using an SEM and optical microscope. The lubricant film on the drawn wire was clearly observed. Therefore, the micro-analysis by SEM provides a way of friction and lubrication assessment in wire drawing.