Abstract
The implantable cuff electrode is an effective neuroprosthetic device in current nerve tissue engineering. However, biocompatibility and stability are still a serious dispute in terms of in vivo function and continuous monitoring. In this regard, assessing the host’s biological response to biomaterials is one of the key factors of chronic implantation. In this article, we analyzed the peripheral nerve specific-biological responses to the application of multi-functional hydrogel-coated electrodes. The surface of the cuff electrode was modified using a multifunctional hydrogel composed of PEG hydrogel, cyclosporin A(CsA)-microsphere(MS) and electrodeposited PEDOT:PSS. Through our approach, we have found that the multifunctional hydrogel coatings improve the neural electrode function, such as peak-to-peak amplitude increase. Additionally, the multifunctional hydrogel coated electrodes exhibited improved biocompatibility, such as reduced apoptotic properties and increased axonal myelination. Furthermore, 12 genes (BDNF, Gfra1, IL-6, Sox 10, S100B, P75NTR, GAP43, MBP, MPZ, NrCAM, NE-FL, CB1) were upregulated at 5 weeks post-implant. Finally, double immunofluorescence revealed the effect of endocannabinoid system on neuroprotective properties and tissue remodeling of peripheral nerves during cuff electrode implantation. These results clearly confirmed that multifunctional hydrogel coatings could improve electrode function and biocompatibility by enhancing neuroprotective properties, which may provide a valuable paradigm for clinical neurology application.
Highlights
Neural prosthetics are promising tool for the rehabilitation of patients with disabled or weakened neuromuscular functions due to nervous system injuries
In the most previous our report, Heo et al devised that the surface-functionalized cuff electrode which was coated with polyethylene glycol (PEG) hydrogel, cyclosporine A (CsA) loaded microsphere, and electrodeposited poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)[20]
1) Bare cuff electrode (Con) 2) Polyethylene glycol (PEG) hydrogel and PEDOT:PSS coated cuff electrode (HP) 3) Microwell-patterned cuff electrode coated with cyclosporine A loaded microsphere (MS) containing PEG
Summary
Neural prosthetics are promising tool for the rehabilitation of patients with disabled or weakened neuromuscular functions due to nervous system injuries. Studies have shown that, in the case of peripheral nerves, gene expression levels such as TNF-α and TGF-β1 could be up-regulated by cuff electrodes[14] For this reason, it is essential to understand the tissue-specific mechanisms of successful/unsuccessful implantation by analyzing biological events at the implant-tissue interface. In the most previous our report, Heo et al devised that the surface-functionalized cuff electrode which was coated with polyethylene glycol (PEG) hydrogel, cyclosporine A (CsA) loaded microsphere, and electrodeposited poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)[20]. From this approach, the functional cuff electrode yielded the enhanced electrochemical effectiveness and reduced inflammatory responses. We estimated the association of endocannabinoid system in enhanced neuroprotective properties of multi-functional hydrogel coated cuff electrodes for in vivo neural interfacing
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