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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 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 nerve, 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 remaining challenges with foreign body response.

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.