Physicochemical and biological functionalisation strategies of the neuroelectrode interface to promote neural integration through the modulation of reactive gliosis
Vallejo Giraldo, Catalina
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Implanted neuroprosthetics and neuroelectrode systems have been under investigation for a number of decades and have been proven to be safe and efficacious as treatments for several neurological disorders including paralysis, epilepsy and Parkinson’s disease as well as for biosensor systems. Neuroelectrode technologies are typically fabricated from metallic conductors such as platinum, iridium and its oxides, materials that while chemically inert and excellent electrical conductors, are often not intrinsically cytocompatible and do not promote integration with neural tissue. The performance of the electrode-tissue interface ultimately rests on the optimisation of the material substrate, to enable chronic functionality. Thus, neural electrodes should present a degree of biomimicry and provide electrical, chemical and physicomechanical properties analogous to neural tissues, with an ultimate goal of mitigating electrode deterioration via reactive host cell response and glial scarinduced encapsulation, which drives neural loss and increases signal impedance, compromising the efficiency of implanted neuromodulation systems. Over several decades of research, studies with conducting polymers as electrode coatings have shown enhanced tissue integration and electrode performance in situ through physichomechanical and biochemical functionalisation. In this thesis, findings on novel topographical and biological functionalisation strategies of conducting polymers, are provided in the context of neurospecific biomaterials, shedding light on the valuable impact of multi-functionalised strategies for biomedical applications. Further, new functionalisation approaches employing an anodisation process of indium-tin oxide (ITO) are outlined as potential electrode materials. At first, a bench-top electrochemical process to formulate anodised ITO films with altered roughness, electrochemical properties and bioactivity was explored. The systematic study shows that anodisation of magnetron sputtered ITO with a current density of 0.4 mA cm-2 results in a well distributed surface morphology, relatively low impedance, electrochemical stability and supported cell viability and neural network activity. Using this current density of 0.4 mA cm-2, PEDOT:PTS neural coating(s) were then electrodeposited for topographical functionalisation via microimprint lithography. The topographical functionalised electrodes reduced adhesion of reactive astrocytes in vitro, as is evident from morphological changes in cell area, focal adhesion formation and the synthesis of pro-inflammatory cytokines and chemokine factors. This work describes the role of micro-topographically modified neural interfaces in the development of stable microelectrode interfaces and reduced gliosis response. Further in the search for biomimicry of the properties analogous to neural tissues, and with an ultimate goal of mitigating electrode deterioration via reactive host cell response and glial scar formation, PEDOT:PTS neural coating were functionalised with the heparan mimetic called F6, first use as a biological dopant in neural coatings. The bio-functionalised PEDOT:PTS:F6 coating show promise as functional neural electrodes and open up opportunities for the use of other glycanic signatures towards the attenuation of inflammation and gliosis with neural trophic characteristics. The biomaterial-tissue interface is not a simple description of a boundary but rather a dynamic interface involving both the localised reaction of the surrounding tissue to the materials, and the material adaptations within the physiological environment. Current research has focused on both the foreign body reaction and the long-term performance of biomaterials in a combined effort to drive the functionalisation of next generation implantable devices. As a result, the improved functionalisation of electrode systems is expected to prompt advancements in the design and development of implantable neural prosthetic devices and medical therapies for neurological disorders.