Cochlear implants (CIs) help to restore basic auditory function in patients who are deaf or have profound hearing loss. However, CI patients suffer from limited voice and tonal perception due to spatial separation between the stimulating CI electrode and the receptor spiral ganglion neurons (SGNs). Directed regeneration of proximate SGN axons may improve tonal performance and implant fidelity by decreasing the spatial separation between the CI electrode and the neural receptor. Additionally, fibrous scar tissue formation on the surface of implanted electrodes further decreases tonal perception through current attenuation and spreading resulting in late-term hearing loss. Thus, designing surfaces that induce favorable responses from neural tissues will be necessary in overcoming signal resolution barriers. In this work, the inherent spatial and temporal control of photopolymerization was used to functionalize surfaces with topographical and biochemical micropatterns that control the outgrowth of neural and other cell types. First, laminin, a cell adhesion protein was patterned using a photodeactivation process onto methacrylate polymer surfaces and was shown to direct the growth of spiral ganglion neurons (SGN), the primary auditory neural receptors. These protein patterns could even overcome low amplitude/high periodicity competing topographical cues. Additionally, glass substrates were patterned with linear zwitterionic polymers and fibroblasts, astrocytes, and Schwann cells all showed dramatically decreased cell adhesion on 100 µm precocity patterns. Further, SGN neurites showed excellent alignment to these same patterns. Next, poly(dimethyl siloxane) (PDMS) was coated with a crosslinked zwitterionic thin film using a single step photografting/photopolymerization process to covalently bind the hydrogel to PDMS. These coated surfaces showed dramatically lower levels of protein, cell, and bacterial adhesion. Finally, zwitterionic hydrogels were strengthened by changing the concentration of poly(ethylene glycol) diacrylate (PEGDA) and 2-hydroxyethyl methacrylate (HEMA) in the formulation. The direct relationship between changing zwitterionic hydrogel formulation to strengthen the hydrogel and the anti-fouling properties were established. The fundamental understanding and design of cochlear implant materials described herein serves as a foundation for the development of next generation neural prosthetics.

Amputation is a life-changing event that results in a drastic reduction in quality of life including extreme loss of function and severe mental, emotional and physical pain. In order to mitigate these negative outcomes, there is great interest in the design of ‘advanced/robotic’ prosthetics that cosmetically and functionally mimic the lost limb. While the robotics side of advanced prosthetics has seen many advances recently, they still provide only a fraction of the natural limbs’ functionality. At the heart of the issue is the interface between the robotic limb and the individual that needs significant development. Amputees retain significant function in their nerves post-amputation, which offers a unique opportunity to interface with the peripheral nerve. Here we evaluate a relatively new approach to peripheral nerve interfacing by using microchannels, which hold the intrinsic ability to record larger neural signals from nerves than previously developed peripheral nerve interfaces. We first demonstrate that microchannel scaffolds are well suited for chronic integration with amputated nerves and promote highly organized nerve regeneration. We then demonstrate the ability to record neural signals, specifically action potentials, using microchannels permanently integrated with electrodes after chronic implantation in a terminal study. Together these studies suggest that microchannels are well suited for chronic implantation and stable peripheral nerve interfacing. As a next step toward clinical translation, we developed fully-integrated high electrode count microchannel interfacing technology capable of functioning while implanted in awake and freely moving animal models as needed for pre-clinical evaluation. Importantly, fabrication techniques were developed that apply to a broad range of flexible devices/sensors benefiting from flexible interconnects, surface mount device (SMD) integration, and/or operation in aqueous environments. Examples include diabetic glucose sensors, flexible skin based health monitors, and the burgeoning flexible wearable technology industry. Finally, we successfully utilized the fully integrated microchannel interfaces to record action potentials in the challenging awake and freely moving animal model validating the microchannel approach for peripheral nerve interfacing. In the end, the findings of these studies help direct and give significant credence to future technology development enabling eventual clinical application of microchannels for peripheral nerve interfacing.

Access to and subsequent control of spinal cord function are critical considerations for design of optimal therapeutic strategies for SCI patients. Electrical stimulation of the spinal cord is capable of activating behaviorally-relevant populations of neurons for recovery of function, and is therefore an attractive target for potential devices. A promising method for accessing these spinal circuits is through their axons, which are organized as longitudinal columns of white matter funiculi along the cord exterior. For this thesis, I hypothesized that these funiculi can be selectively recruited via electrodes appropriately placed on the surface of the spinal cord, for functional activation of relevant motor circuitry in a chronically-transected spinal cord. My tandem design goal was to fabricate and implement a conformable multi-electrode array (MEA) that would enable this selective stimulation. To accomplish this design goal, I participated in the design, fabrication, and electromechanical testing of a conformable MEA for surface stimulation of spinal tracts. I then assessed the fundamental capability of this MEA technology to stimulate white matter tracts in a precise, controlled, and functionally-relevant manner. This was accomplished via in vitro experiments that explored the ability of this MEA to locally activate axons via single- and dual-site surface stimulation. The results from these evaluation studies suggest that spinal-cord surface stimulation with this novel MEA technology can provide discrete, minimally-damaging activation of spinal systems via their white matter tracts. To test my hypothesis that surface stimulation can be used to recruit distinct populations in the spinal cord, I performed studies that stimulated lateral funiculi in both chronically-transected and intact in vitro spinal cords. Results from these studies reveal that selective surface stimulation of white matter tracts in the ventrolateral funiculus (VLF) elicit motor outputs not elicited in intact cords. In addition, I was able to demonstrate that the spinal systems activated by this surface stimulation involve synaptic components and are responsive to spatial, temporal, and pharmacologic facilitation. Corresponding labeling of the axonal tracts projecting through the T12 VLF indicate that, after chronic transection, the remaining spinal neurons whose axons travel through the VLF include those with cell bodies in both the intermediate region and dorsal horn. These electrophysiological results show that surface-stimulating technologies used to control motor function after injury should include focal activation of interneuronal systems with axons in the ventrolateral funiculus. As a whole, these studies provide essential starting points for further use of conformable MEAs to effectively activate and control spinal cord function from the surface of the spinal cord.

The emerging research field of Brain Computer Interfaces (BCIs) has created an invasive type of BCI, the Cortical Motor Prosthetic (CMP) or invasive BCI (iBCI). The goal is to restore lost motor function via prosthetic control signals to individuals who have long-term paralysis. The development of the CMP consists of two major entities: the implantable, chronic microelectrode array (MEA) and the data acquisition hardware (DAQ) specifically the decoder. The iBCI's function is to record primary motor cortex (M1) neural signals via chronic MEA and translate into a motor command via decoder extraction algorithms that can control a prosthetic to perform the intended movement. The ultimate goal is to use the iBCI as a clinical tool for individuals with long-term paralysis to regain lost motor functioning. Thus, the iBCI is a beacon of hope that could enable individuals to independently perform daily activities and interact once again with their environment. This review seeks to accomplish two major goals. First, elaborate upon the development of the iBCI and focus on the advancements and efforts to create a viable system. Second, illustrate the exciting improvements in the iBCI's use for reaching and grasping actions and in human clinical trials. The ultimate goal is to use the iBCI as a clinical tool for individuals with long-term paralysis to regain movement control. Despite the promise in the iBCI, many challenges, which are described in this review, persist and must be overcome before the iBCI can be a viable tool for individuals with long-term. iBCI future endeavors aim to overcome the challenges and develop an efficient system enhancing the lives of many living with paralysis. Standard terms: Intracortical Brain Computer Interface (iBCI), Intracortical Brain Machine Interface (iBMI), Cortical Motor Prosthetic (CMP), Neuromotor Prostheses (NMP), Intracortical Neural Prosthetics, Invasive Neural Prosthetic all terms used interchangeably

Numerous applications in neuroscience research and neural prosthetics, such as retinal prostheses, spinal-cord surface stimulation for prosthetics, electrocorticogram (ECoG) recording for epilepsy detection, etc., involve electrical interaction with soft excitable tissues using a surface stimulation and/or recording approach. These applications require an interface that is able to set up electrical communications with a high throughput between electronics and the excitable tissue and that can dynamically conform to the shape of the soft tissue. Being a compliant and biocompatible material with mechanical impedance close to that of soft tissues, polydimethylsiloxane (PDMS) offers excellent potential as the substrate material for such neural interfaces. However, fabrication of electrical functionalities on PDMS has long been very challenging. This thesis work has successfully overcome many challenges associated with PDMS-based microfabrication and achieved an integrated technology platform for PDMS-based stretchable microelectrode arrays (sMEAs). This platform features a set of technological advances: (1) we have fabricated uniform current density profile microelectrodes as small as 10 microns in diameter; (2) we have patterned high-resolution (feature as small as 10 microns), high-density (pitch as small as 20 microns) thin-film gold interconnects on PDMS substrate; (3) we have developed a multilayer wiring interconnect technology within the PDMS substrate to further boost the achievable integration density of such sMEA; and (4) we have invented a bonding technology---via-bonding---to facilitate high-resolution, high-density integration of the sMEA with integrated circuits (ICs) to form a compact implant. Taken together, this platform provides a high-resolution, high-density integrated system solution for neural and muscular surface interfacing. sMEAs of example designs are evaluated through in vitro and in vivo experimentations on their biocompatibility, surface conformability, and surface recording/stimulation capabilities, with a focus on epimysial (i.e. on the surface of muscle) applications. Finally, as an example medical application, we investigate a prosthesis for unilateral vocal cord paralysis (UVCP) based on simultaneous multichannel epimysial recording and stimulation.