The work reported in this thesis is motivated by the need for wireless powering of a miniaturized implantable device for neurophysiological research and possible clinical applications. The antenna used in such applications must be studied in the context of biological tissue media. In this thesis, we perform a preliminary study of antenna behaviour in the complex tissue environment. Our test cases are the wire dipole antenna chosen for its structural simplicity and the spiral antenna, selected for its wide bandwidth. The simulation tool SEMCAD-X, is based on the Finite-Difference Time-Domain (FDTD) method and is used throughout this work. To have an in-depth understanding of the characteristics of different solvers implemented in SEMCAD-X and relevant for our applications, we first simulate the antenna structures in the free-space region using both SEMCAD-X and HFSS (a Finite-Element Method (FEM) simulation software). The cross-platform comparison between these two simulation tools helps us identify the advantages of using conformal FDTD solver over the conventional staircase FDTD solver in SEMCAD-X. We then embed the antennas in tissue-like non-homogeneous lossy media to observe the terminal voltages induced by an impinging plane-wave. These numerical experiments will help us with the assessment of the following: variations of antenna properties with the in-tissue locations, and more importantly the dependence of the induced voltage on the depth of the implant.

Biomaterial surface properties such as microtopography and energy can change cellular responses at the cell-implant interface. Phospholipase D (PLD) is required for differentiation of osteoblast-like MG63 cells on machined and grit-blasted titanium surfaces. Here, we determined if PLD is also required on microstructured/high-energy substrates and the mechanism involved. shRNAs for human PLD1 and PLD2 were used to silence MG63 cells. Wild-type and PLD1 or PLD1/2 silenced cells were cultured on smooth-pretreatment surfaces (PT); grit-blasted, acid-etched surfaces (SLA); and SLA surfaces modified to have higher surface energy (modSLA). PLD was inhibited with ethanol or activated with 24,25-dihydroxyvitamin-D₃ [24R,25(OH)₂D₃]. As surface roughness/energy increased, PLD mRNA and activity increased, cell number decreased, osteocalcin and osteoprotegerin increased, and protein kinase C (PKC) and alkaline phosphatase specific activities increased. Ethanol inhibited PLD and reduced surface effects on these parameters. There was no effect on these parameters after knockdown of PLD1, but PLD1/2 double knockdown had effects comparable to PLD inhibition. 24R,25(OH)₂D₃increased PLD activity and production of osteocalcin and osteoprotegerin, but decreased cell number on the rough/high-energy surfaces. These results confirm that surface roughness/energy-induced PLD activity is required for osteoblast differentiation and that PLD2 is the main isoform involved in this pathway. Here we showed that PLD is activated by 24R,25(OH)₂D₃ in a surface-dependent manner and inhibition of PLD reduced the effects of surface microstructure/energy on PKC, suggesting that PLD mediates the stimulatory effect of microstructured/high-energy surfaces via PKC-dependent signaling.

Patients who have undergone treatment that has included the surgical implantation of a prosthetic device can become dissatisfied for many reasons. One cause for dissatisfaction is any adverse event where there is a demonstrable causal nexus with the failure of a device that is defective or at risk of being so. The magnitude of therapeutic product failure is considerable and therapeutic goods such as Vioxx, Thalidomide, silicon-gel-filled breast implants, contaminated blood products, cardiac pacemakers and valves, and orthopaedic devices are testimony to this. Many of these events have exposed a greyish area of Australian law that balances medical negligence with consumer protection and contract law. Australian product liability legislation that regulates the use of therapeutic goods is a complex amalgam of law that has at its foundations the Trade Practices Act 1974 (Cth) and the Therapeutic Goods Act 1989 (Cth). When a surgical device fails there can be exposure to liability. This thesis explores those important issues that can impact on individuals or on organisations and it is evident that where issues of product liability concern implanted surgical devices the current regulations for consumer protection may not always be the most appropriate. It is evident that there is a culture of under-reporting of adverse events to a Therapeutic Good Administration that does not have the resources to investigate the cause for failure of a surgical device. Furthermore, there is a potential for bias and conflict of interest in an environment where the regulator depends on the regulated for the funding of its existence. Other issues include the complex and often undesirable consequences of those partnerships that can evolve with the development of an implantable device and with the undertaking of clinical trials, the role of the learned intermediary, that interface between manufacturer and consumer, and the role of the expert witness, that interface between justice and injustice. These and other matters that can significantly influence any debate of implantable surgical device product liability are explored and recommendations are made that might form the basis of a Therapeutic Goods (Safe Medical Devices) Amendment Act.

The use of metals like titanium (Ti) and vanadium (V) are common in many medical implants for orthopaedic and orthodontic purposes. The most frequent cause of implant failure is aseptic loosening, resulting from an inflammatory reaction and increased osteolysis at the bone-metal interface. Currently, the pathophysiological mechanism of aseptic loosening remains poorly understood. One hypothesis suggests the reactivity of immune cells (metal hypersensitivity) towards metal ions released through the biocorrosion of metal implants. This thesis examines the effects of titanium and vanadium ions on various immune cells like monocytes, dendritic cells (DCs) and T-lymphocytes. Thereby investigating the role and mechanism which titanium and vanadium plays in aseptic loosening. Through energy filtered transmission electron microscopy, the accumulation of titanium ions was visualized in human monocyte-derived DCs and T-lymphocytes after 24 hours exposure. Titanium was seen to co-localise with phosphorous-rich regions, like the cell membrane, organelles and nucleus of these cells. Flow cytometry measured changes in the cell surface marker expression of monocytes, osteoclasts, DCs and T-lymphocytes treated with the metals. Monocytes exposed to titanium (IV) showed an increase of Tartate-Resistant Acid Phosphatase (TRAP), important for osteolysis and indicative of differentiation towards an osteoclast-like phenotype. DCs treated with Ti(IV) and vanadium (III) had reduced antigen presenting MHC class II expression, but not a reduced capacity to proliferate non-adherent peripheral blood monocytic cells (naPBMCs). Under the influence of Ti(IV), T-lymphocytes, DCs and monocytes expressed elevated levels of the chemokine receptor, CCR4. This would allow for the migration of CCR4+ cells towards the bone and skin regions. Functional changes were measured with BrdU incorporation proliferation assays, cytokine assays (CBA Kits) and the successful generation of titanium-specific T-lymphocytes from Ti(IV) treated DCs. Ti(IV) specific T-lymphocytes conceptually shows the possible formation of an antigenic titanium-protein complex, which can be recognized by the immune system. DCs treated with Ti(IV) and V(III) were able to cause the proliferation of naPBMCs, even with a reduced antigen presenting capability. However, there was no additional influence of V(III) on the immune response through DCs. Cytokines released by DCs and T-lymphocytes after Ti(IV) treatments showed a skew towards an inflammatory Th1-type response through the release of TGF-! and IL-12p70. Activated T-lymphocytes exposed to Ti(IV) also released RANK-L, which drives osteoclastogenesis and subsequently increased osteolysis. The research supports and suggests an interaction between immune and bone cells where titanium-induced inflammation drives an osteolytic cycle that prevents the integration of metal implants into the bone. Hence, suggesting a mechanism for implant failure through aseptic loosening in patients with titanium-vanadium implants.

Thesis (Ph.D.)--University of Adelaide, Dept. of Orhtopaedics and Trauma, 1998. / Bibliography: leaves 198-219.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (Ph.D.) -- Mississippi State University. Dave C. Swalm School of Chemical Engineering. / Title from title screen. Includes bibliographical references.

Thesis (M. Sc.)--University of Canterbury, 2009. / Typescript (photocopy). "June 2009." Includes bibliographical references (p. [113]-119).

Thesis (M.S.)--University of Michigan, 1987.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.