Electrochemical Safety Studies of Cochlear Implant Electrodes Using the Finite Element Method

Cochlear implants, amongst other neural prostheses, utilise platinum electrodes as an interface between the synthetic implant and the biological tissue environment. If excessive electrical charge is injected via these electrodes, injury to the tissue may result. Empirically derived stimulation limits have been defined to prevent tissue damage, however the injurious mechanisms are still unclear. Evidence suggests that the non-uniform distribution of charge on electrodes influences the electrochemical generation of toxic by-products. However, in vivo and in vitro techniques are limited in their ability to systematically explore the factors and mechanisms that contribute to stimulation-induced tissue injury. To this end, an in silico approach was used to develop a time-domain model of cochlear implant stimulation electrodes. A constant phase angle impedance was used to model the reversible processes on the electrode surface, and Butler-Volmer reaction kinetics were used to define the behaviour of the water window irreversible electrochemical reactions. The resulting model provided time-domain responses of the current density distributions, and net charge consumed by the hydrolysis reactions. This model was then used to perform systematic evaluations of various electrode geometries and stimulation parameters. The modelling results showed the current associated with irreversible reactions was non-uniform and tended towards the periphery of the electrode. A comparison of electrode geometries revealed interactions between electrode size, shape and recess depth. Stimulation mode, electrode position, and electrolyte conductivity were found to impact the shape of the electric field and the extent of irreversible reactions. This emphasised the influence of the physiological environment on the stimulation safety. In vitro experiments were conducted to validate the model. The implications of the results described in this thesis can be used to inform the design of safer electrodes

Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging

Yielding behaviors of polymeric scaffolds with implications to tissue engineering

Polymers are amongst the main candidate materials for load bearing tissue engineering scaffolds. Their effective and reliable clinical uses necessitate insightful analyses of the nonlinear characteristics, which has so far received little attention in literature. To better understand the failure characteristics of these porous structures, yielding behaviors of scaffolds made of a commercial photopolymer (RGD720) were studied using experiments and finite element method (FEM). The polymer exhibits substantial softening under uniaxial material test, but the extent of such softening behavior in a scaffold structure is compromised or even eliminated due to the internal non-uniformity of material yielding