Physicochemical and biological functionalisation strategies of the neuroelectrode interface to promote neural integration through the modulation of reactive gliosis
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.2021-12-0
