Table 3.

Nanoengineered Electroconductive Scaffolds for Neural Tissue Regeneration

Type of conductive scaffolds	Composition	Fabrication technique	Measurement device	Cellular type	Properties (with focus on electrical properties and requirements)	Disadvantages and future directions	Ref.
Composite hydrogel	OPF/CNTs/GO	Covalent embedding	34461A digital multimeter	PC-12 cells (cells from rat's pheochromocytoma), Rattus norvegicus, adrenal gland of rat	A synergistic effect of electrical conductivity and positive charges on nerve cells was observed Conductivity values of (3.16 ± 1.39) × 10−4 S/m for pure OPF hydrogel, (6.24 ± 2.70) × 10−4 S/m for OPF-MTAC hydrogel, and (2.96 ± 1.86) × 10−3 S/m for OPF-rGO-CNTpega hydrogel were reposted	Enhanced proliferation and spreading of PC12 cells Great potential as conduits for neural tissue engineering NGF was used to stimulate the cells effectively	81
3D printed scaffold	PPy–polycaprolactone	EHD jet 3D printing process	Conductivity meter (pH/Ion meter S220)	hESC-NCSCs	PPy/PCL scaffolds possess conductivity ranging from 0.28 to 1.15 mS/cm depending on concentration of PPy The conductivity value for the PCL/PPy (1% v/v), which showed the most maturation of hESC-NCSCs was about 1.02 ± 0.03 mS/cm	The most attachment and differentiation of hESC-NCSCs to peripheral neurons was observed on PCL/PPy (1% v/v) Potential treatment of neurodegenerative disorders, however no in vivo studies were executed in this study	82
Composite microporous tube	PVDF–PCL	Cast/annealing-solvent displacement method	PFM suing AFM	RSCs	Electroconductive PVDF/PCL scaffolds have a positive effect on myelination, axon regeneration, as well as angiogenesis, which all contribute to nerve regeneration and attenuates muscle denervation	Implanted PVDF/PCL scaffolds into the 15-mm defect rat sciatic nerve model	83
Hybrid/composite	POSS–PCL–Graphene	Simple blending, sonication, and casting	EIS	Neonatal Wistar rat SCs	The percolation threshold occurred at 0.08 wt% graphene At 4.0 wt% the electrical conductivity exceeded 10−4 S/cm Conductivity values were reported as 8.76 × 10−14 S/cm, 3.47 × 10−11 S/cm, 1.49 × 10−7, and 9.34 × 10−5 for pristine POSS-PCL, and POSS-PCL incorporated with 0.4, 1.6, 4 wt% graphene, respectively	OSS-PCL/graphene nanocomposites showed higher metabolic activity and cell proliferation in comparison with pristine POSS-PCL	84
Microribbons	PLGA–Graphene	Wet spinning	Four-point probe electrical station	Human neuroblastoma cell line SH-SY5Y	Conductivity value of 0.15 ± 0.01 μS/m for pristine PLGA, while incorporation of 1 wt% Gr nanosheets induced a conductivity of 0.42 ± 0.03 S/m	Lack of in vivo studies that show these PLGA/Graphene microribbons can stimulate neural stem cell function	85
3D Braided filaments	SF-PCL-CNFs	Home-made coating system	Impedance analyzer	N2a mouse neural crest-derived cell	By increasing the CNF in the coating, the electrical impedance decreased up to 400 Ω The lowest impedance of 316 ± 3.42 Ω/mm was observed for the highest concentration of CNFs at a frequency of 20 MHz	Lack of in vivo studies Potential use for successful regeneration of a 15–20 cm nerve gap	86
Hybrid electrospun scaffold	PHA–Graphene –gold nanoparticles	Electrospinning	NA	PC-12 cells and SCs	Conductivity measurements were not performed	PHA–RGO–Au scaffolds prominently endorsed SCs proliferation and migration No data on the conductivity values of the scaffolds were reported Lack of enough data to conclude the ability of the engineered scaffolds in peripheral nerve regeneration	87
Hybrid nanocomposite scaffold	PVDF–GO	Nonsolvent induced phase separation method	EIS-ARSTAT 2273,	Rat neuronal PC-12 cells	Incorporation of GO nanosheets into the PVDF scaffold simultaneously enhanced β-phase fraction, piezoelectricity, and electrical conductivity Incorporation of 1 wt% GO into PVDF, reduced impedance value from 804.6 ± 53.4 to 105.7 ± 32.45 Ω	PVDF–GO scaffolds significantly promoted PC12 cell proliferation, compared with pristine PVDF scaffold	88
CNT-based scaffolds	Graphene sheets	Chemical vapor deposition, Electric arc discharge, Laser ablation	Single-cell patch clamp recording	Neurons (PC-12 cells)	Sheets of graphene formed into cylinders that can be single walled, double walled, and multiwalled 71 Neural interfaces formed as a microchip on a quartz substrate using plasma etching and photolithography Flexibility and bioconductivity CNT-based scaffolds used as substrates for neural cell growth	Lack of solubility in aqueous media; Surface modification with hydrophilic molecules is the method used to overcome this disadvantage89	90,91
Substrate-bound transistors and electrodes	Silicon nanowires and graphene	Evaporation	STM	Neurons	There are three terminals for transistors: source, drain, gate Electric field is generated by voltage applied to the gate92 An electrically neutral area is required around transistors and microelectrodes and also a cascade of enzymes to transmit signals93 Tumor enhancement for imaging through transferring excitatory stimuli	Electroactivity of different molecules in the brain that can interfere with microelectrodes and sensors; Nafion barriers are used to decrease impulse interfering93	69

CNFs, carbon nanofibers; EHD, electrohydrodynamic; GO, graphene oxide; hESC-NCSCs, human embryonic stem cell-derived neural crest stem cells; N2a, neuro 2A; NPF, nerve growth factor; PFM, piezoresponse force microscopy; PHA, polyhydroxyl alkanoate; POSS, polyhedral oligomeric silsesquioxane; OPF, oligo(poly(ethylene glycol) fumarate); RSCs, rat Schwann cells; SCs, Schwann cells; SF, silk fibroin; STM, scanning tunneling microscope.