Designing neural-electrode interfaces that maintain close physical coupling of neurons to the electrode surface remains a major challenge for both implantable and in vitro neural recording electrode arrays. Typically, low-impedance nanostructured electrode coatings rely on chemical cues from pharmaceuticals or surface-immobilized peptides to suppress glial scar tissue formation over the electrode surface (astrogliosis), which is an obstacle to reliable neuron-electrode coupling. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising candidate to reduce astrogliosis solely through topography by taking advantage of its tunable length scale. In the present in vitro study on np-Au’s interaction with cortical neuron-glia co-cultures, we demonstrate that the nanostructure of np-Au is achieving close physical coupling of neurons through maintaining a high neuron-to-astrocyte surface coverage ratio. Atomic layer deposition-based surface modification was employed to decouple the effect of morphology from surface chemistry. Additionally, length scale effects were systematically studied by controlling the characteristic feature size of np-Au through variations of the dealloying conditions. Our results show that np-Au nanotopography, not surface chemistry, reduces astrocyte surface coverage while maintaining high neuronal coverage, and may enhance the neuron-electrode coupling through nanostructure-mediated suppression of scar tissue formation.
Nanostructured neural interface coatings have significantly enhanced recording fidelity in both implantable and in vitro devices. As such, nano-porous gold (np-Au) has shown promise as a multifunctional neural interface coating due, in part, to its ability to promote nanostructure-mediated reduction in astrocytic surface coverage while not affecting neuronal coverage. The goal of this study is to provide insight into the mechanisms by which the np-Au nanostructure drives the differential response of neurons versus astrocytes in an in vitro model. Utilizing microfabricated libraries that display varying feature sizes of np-Au, it is demonstrated that np-Au influ-ences neural cell coverage through modulating focal adhesion formation in a feature size-dependent manner. The results here show that surfaces with small (≈30 nm) features control astrocyte spreading through inhibition of focal adhesion formation, while surfaces with large (≈170 nm and greater) features control astrocyte spreading through other mechanotransduction mechanisms. This cellular response combined with lower electrical impedance of np-Au electrodes significantly enhances the fidelity and stability of electrophysiological recordings from cortical neuronglia co-cultures relative to smooth gold electrodes. Finally, by leveraging the effect of nanostructure on neuronal versus glial cell attachment, the use of laser-based nanostructure modulation is demonstrated for selectively patterning neurons with micrometer spatial resolution.
Localized and actively controlled delivery of drugs presents an opportunity for improving bioavailability, therapeutic efficacy, and long-term treatment of injury or disease. Conductive polymer (CP) based systems present a unique opportunity for using inherent electrochemical and actuating properties to ensure that drugs are delivered or retained using charge controlled mechanisms. A number of CP formats have been explored spanning CP films, composites of CPs with polymeric carriers, and organic electronic ion pumps (OEIPs). Each of these designs can be used to deliver drugs with ionic properties that take advantage of the doping and dedoping characteristics of CPs during electrical pulsing or cycling. However, CP composites that use actuation and OEIPs are emerging technologies that can better address the need for the delivery of a wide range of drugs with varying net charge properties. These systems also allow a high drug loading profile, and with an appropriate configuration, they can use additional electrodes to drive drugs into the tissues. There are also innovative opportunities in the delivery of multiple drug types with varying charge properties that can be individually addressed. The future of CP based drug delivery systems will be strongly influenced by translational challenges including the need for regulatory approvals prior to the use of these novel material platforms in the clinic. Multidisciplinary collaboration will be critical to driving technology development and creating a new paradigm in personalized bioelectronic delivery of therapeutics.
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