Electrochemical Evaluation of Layer-by-Layer Drug Delivery Coating for Neural Interfaces.

Intracortical microelectrode arrays (MEAs) are valuable tools for neuroscience research, and their potential clinical use has been demonstrated. However, their inability to function reliably over chronic time points has limited their clinical translation. MEA failure is highly correlated with foreign body response (FBR), and therapeutics have been used to reduce FBR and improve device function, with drugs such as minocycline showing promising results in vivo. To avoid issues associated with systemic drug delivery, device coatings can be used to for therapeutic delivery. One method to locally deliver minocycline is a layer-by-layer (LBL) coating that consists of multiple trilayers of gelatin type A, minocycline, and dextran sulfate; however, the coating's impact on device function was previously unknown. This work characterized 10, 20, and 30 trilayer coatings and then evaluated their effect on device function. Cumulative minocycline release and coating thickness increased with the number of trilayers, agreeing with observations in previous studies. Atomic force microscopy images were used to calculate surface roughness of the coatings, which significantly increased from 10 to 20 trilayers and then remained relatively constant upon increasing to 30 trilayers. Scanning electron microscopy images confirmed that trilayers coated the MEAs. Electrochemical impedance spectroscopy (EIS) and charge carrying capacity (CCC) were used to evaluate the coating's effect on MEA electrochemical behavior over 3 weeks while the coated MEAs soaked in PBS. The 10 trilayer coatings slightly decreased CCC, while 20 and 30 trilayers initially increased CCC. CCC of all trilayers gradually increased as the MEAs soaked in PBS. All trilayers initially increased MEA impedance magnitude and reduced the phase angle at low frequencies. Impedance magnitude at 1 kHz and 15 kHz decreased toward their initial precoated values for all trilayers as the MEAs soaked in PBS. Overall, these results show that the LBL coatings did not significantly impact MEA function.

Tissue-Engineered Peripheral Nerve Interfaces.

Research on neural interfaces has historically concentrated on development of systems for the brain; however, there is increasing interest in peripheral nerve interfaces (PNIs) that could provide benefit when peripheral nerve function is compromised, such as for amputees. Efforts focus on designing scalable and high-performance sensory and motor peripheral nervous system interfaces. Current PNIs face several design challenges such as undersampling of signals from the thousands of axons, nerve-fiber selectivity, and device-tissue integration. To improve PNIs, several researchers have turned to tissue engineering. Peripheral nerve tissue engineering has focused on designing regeneration scaffolds that mimic normal nerve extracellular matrix composition, provide advanced microarchitecture to stimulate cell migration, and have mechanical properties like the native nerve. By combining PNIs with tissue engineering, the goal is to promote natural axon regeneration into the devices to facilitate close contact with electrodes; in contrast, traditional PNIs rely on insertion or placement of electrodes into or around existing nerves, or do not utilize materials to actively facilitate axon regeneration. This review presents the state-of-the-art of PNIs and nerve tissue engineering, highlights recent approaches to combine neural-interface technology and tissue engineering, and addresses the remaining challenges with foreign-body response.

Foreign Body Response to Intracortical Microelectrodes Is Not Altered with Dip-Coating of Polyethylene Glycol (PEG).

Poly(ethylene glycol) (PEG) is a frequently used polymer for neural implants due to its biocompatible property. As a follow-up to our recent study that used PEG for stiffening flexible neural probes, we have evaluated the biological implications of using devices dip-coated with PEG for chronic neural implants. Mice (wild-type and CX3CR1-GFP) received bilateral implants within the sensorimotor cortex, one hemisphere with a PEG-coated probe and the other with a non-coated probe for 4 weeks. Quantitative analyses were performed using biomarkers for activated microglia/macrophages, astrocytes, blood-brain barrier leakage, and neuronal nuclei to determine the degree of foreign body response (FBR) resulting from the implanted microelectrodes. Despite its well-known acute anti-biofouling property, we observed that PEG-coated devices caused no significantly different FBR compared to non-coated controls at 4 weeks. A repetition using CX3CR1-GFP mice cohort showed similar results. Our histological findings suggest that there is no significant impact of acute delivery of PEG on the FBR in the long-term, and that temporary increase in the device footprint due to the coating of PEG also does not have a significant impact. Large variability seen within the same treatment group also implies that avoiding large superficial vasculature during implantation is not sufficient to minimize inter-animal variability.

The effect of multiple thin-film coatings of protein loaded sol-gel on total multi-electrode array thickness.

Tetramethyl orthosilicate shows promise as a thin-film delivery vehicle for multi-electrode arrays for drug release and electrical performance; however, its effect upon device footprint has yet to be assessed. Using a previously established silicon wafer chip model, the thickness of one, two, and four protein doped coatings of sol-gel were analyzed via profilometry. Coating thickness was found to be 0.4µm, 1.1µm and 2.2µm on each side of the device. This addition to a native MEA is minimal when compared to other drug delivery paradigms currently associated with neural implants.