Enhanced nerve cell proliferation and differentiation on electrically conductive scaffolds embedded with graphene and carbon nanotubes

Abstract

Conduits that promote nerve regeneration are currently of great medical concern, particularly when gaps exist between nerve endings. To address this issue, our laboratory previously developed a nerve conduit from biodegradable poly(caprolactone fumarate) (PCLF) that supports peripheral nerve regeneration. The present study improves upon this work by further developing an electrically conductive, positively charged PCLF scaffold through the incorporation of graphene, carbon nanotubes (CNTs), and [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MTAC) (PCLF-Graphene-CNT-MTAC) using ultraviolet (UV) induced photocrosslinking. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy were used to assess the incorporation of CNTs and graphene into PCLF-Graphene-CNT-MTAC scaffolds, which displayed enhanced surface roughness and reduced electrochemical impedance when compared to neat PCLF. Scaffolds with these surface modifications also showed improved growth and differentiation of rat pheochromocytoma 12 cells in vitro, with enhanced cell growth, neurite extension, and cellular migration. Furthermore, an increased number of neurite protrusions were observed when the conduit was electrically stimulated. These results show that the electrically conductive PCLF-Graphene-CNT-MTAC nerve scaffolds presented here support the cellular behaviors that are critical for nerve regeneration, ultimately making this material an attractive candidate for regenerative medicine applications.

Electro-responsive polymer-based platforms for electrostimulation of cells

“…1,5,[59][60][61][62] Several electro-responsive polymers are used in the development of advanced conductive cell culture/tissue engineering scaffolds, including those from the conjugated polymer family poly(pyrrole) (PPy), [63][64][65][66] polyaniline (PANI), [67][68][69][70][71] poly(3,4-ethylene dioxythiophene) (PEDOT)), [72][73][74][75] and polysaccharides (chitosan (CS)), [76][77][78][79][80][81][82] hyaluronic acid (HA), 83 and alginate (ALG). 84,85 Conductive scaffolds are also commonly obtained by combining highly conductive carbon-based materials (e.g., carbon nanotubes (CNTs), [86][87][88][89] multiwalled carbon nanotubes (MWCNTs), 79,90,91 graphene (GR), [92][93][94] graphene oxide (GO) 95 and reduced graphene oxide (rGO)) 96,97 with non-conductive polymers such as poly(lactic acid) (PLA), poly(-caprolactone) (PCL), poly(ethylene glycol) (PEG), collagen and its derivatives.…”

“…83,84 Conductive scaffolds are also commonly obtained by combining highly conductive carbon-based materials ( e.g. , carbon nanotubes (CNTs), 85–88 multiwalled carbon nanotubes (MWCNTs), 78,89,90 graphene (GR), 91–93 graphene oxide (GO) 94 and reduced graphene oxide (rGO)) 95,96 with non-conductive polymers such as poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), collagen and its derivatives.…”

Advances in Triboelectric Nanogenerators for Self‐Powered Regenerative Medicine

“…Peripheral nerve injury is a prevalent global clinical disability that is often followed by incomplete recovery. [161][162][163] Conventional electrical neuromodulation therapies that are invasive or non-invasive, are applied to the PNS to restore motor function in paralyzed limbs, provide intuitive sensory feedback in limb prostheses, and elicit a network of positive physiological responses. [164][165][166] Despite the positive therapeutic response from ES in PNS, several challenges are still prevalent, including miniaturization, combination of different electronic components, improvements in the fabrication of flexible and stretchable substrates with high biocompatibility for implantable devices, and enhancement of device packaging.…”

Perspectives on 3D Bioprinting of Peripheral Nerve Conduits

“…Graphene and carbon nanotubes have been used as biocompatible, non-immunogenic conductive composite materials in experimental nerve conduit models [ 72 ]. Gelatin- and graphene-incorporated nerve guidance conduits were printed to make conductive conduits [ 73 ]. The 3D-printed conductive block copolymer of PPy and PCL (PPy-b-PCL), and pure PCL nerve conduits were evaluated in vitro.…”