Abstract
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.
Highlights
Implantable neural probes hold the promise of providing functional recovery to individuals suffering from traumatic injuries or neurological disorders (Taylor et al, 2002; Hochberg et al, 2012)
This microglial activity was identified by co-localization of green fluorescent protein (GFP) with CD68 immunoreactivity
Of the microglia co-localized with CD68 near the implant track, no particular morphological differences were noted between Poly(ethylene glycol) (PEG)-coat and no-coat groups
Summary
Implantable neural probes hold the promise of providing functional recovery to individuals suffering from traumatic injuries or neurological disorders (Taylor et al, 2002; Hochberg et al, 2012). In an attempt to resolve the Tissue Responses to PEG-Coated Microelectrodes biological aspects of this issue, researchers have modulated multiple factors including: device architecture/material type/flexibility (Seymour and Kipke, 2007; Karumbaiah et al, 2013; Xie et al, 2015; Lee et al, 2017a,b; Luan et al, 2017), bioactive coatings (Pierce et al, 2009; Azemi et al, 2011; Kozai et al, 2012a; Rao et al, 2012), and drug delivery schemes (Shain et al, 2003; Zhong and Bellamkonda, 2007) In parallel to these engineering mitigation strategies, there are ongoing attempts to discover the precise biotic and abiotic mechanisms of implant failure in order to develop strategies to improve the functional lifetime of neural implants (Barrese et al, 2013, 2016). Reducing the FBR has been considered essential to achieve long-term functionality of neural implants
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