Table 1.

Strategies for improving microelectrode arrays

MEA Modifications	Surface Features/MEA Properties	Neural Cell Adhesion/Protein Adsorption	Neural Cell Grow/Loss	Foreign Body Response (FBR)	Signal Maintenance/MEA Longevity	References
Improving Surface Chemistry
Natural materials
Avitene™-MCH	White, cotton-like appearance; Collagen I, Collagen III, Collagen VI, and Lumican components	N/A	Large amounts of activated microglial growth; limited ramified microglial growth	No significant reduction in FBR compared to control	N/A	61
Neuroadhesive L1	Neuronal adhesion molecule	83% reduction in microglial adhesion; Good neuronal adhesion	Good neuroblast growth; limited neuronal cell death	Reduction in overall gliosis	N/A	64, 65a, 65b
Natural ECM	Vary depending on ECM coating type (i.e. astrocyte-derived coating: Collagen VI, Collagen XII, Tenascin N & W, Perlecan, Thromobospondin-1, Fetuin A)	Good neuronal cell adhesion	Limited neuronal cell death	Microglial suppression; reduction of astrogliosis	No significant electrode impedance following coat application	61, 62, 63
Sodium alginate	Na, C, N, and O surface chemistry; 400 μm thick coating	N/A	Limited neuronal cell death	Limited immunoreactivity	N/A	71
Synthetic materials
Silica sol-gel	Smooth to rough texture, depending on composition (i.e. octyl, phenyl, aminopropyl, vinyl, glycidyl, octadecyl, thiol, isocyanate, chlorine, or iodine groups)	Good neuronal cell adhesion	Good neurite outgrowth; limited astrocyte growth	Limited FBR	N/A	66
PEDOT	Various different properties (i.e. fine textured porous surface with thin nanofilaments)	Reduced microglial adhesion	Limited neuronal cell death	Less severe FBR	Enhanced charge storage capacity and signal maintenance; enhanced noise and artifact reduction; PEDOT films increased MEA performance compared to controls during experimental period	67a, 67b, 67c
SOD Mimetic	MnTBAP-antioxidant coating	N/A	Limited cytotoxicity	Reduced microglial activity and superoxide radical production	Good shielding against reactive oxygen species	70
Nanomaterials/Nanostructures	Carbon nanotubules on platinum cochlear neural electrodes	Stable cell adhesion	Stable cell growth	N/A	Decreased impedance and increased capacitance	69
	Polypyrrol nanotubes augmented with gold nanoparticles	N/A	No significant cytotoxicity	N/A	Tenfold decrease in electrochemical impedance	68
Improving Surface Topography
Parallel nano/micro groves	Nanopatterned parallel grooves 200 nm wide, 200nm deep, and 300 nm spacing	No significant difference in cell adhesion	Larger neuronal density at 4 weeks post implantation compared to control	No significant reduction of neuroinflammation	Nanopatterned groves did not degrade during study period	77
Nano/micro pillars	Microscale pillars with interspacings of 6-8 μm	Inhibition of platelet adsorption	N/A	N/A	N/A	59a
	580-800 nm long, 150-200 nm diameter nanopillars	Decent neural cell adhesion	More stable neural cell density compared to other tested topographies	No significant difference to control or other implants	N/A	78
Nano/micro pores	Nanoporous gold surface	Increased neuronal cell coverage, decreased astrocytic coverage	Good neural cell growth	Reduced glial scar formation	Might enhance neuron-electrode coupling	74
Improving Surface Geometry
Smaller MEAs	15 μm Michigan electrodes and microwire electrodes	N/A	Lower neuronal cell loss compared to larger electrodes	Less severe FBR compared to larger electrodes	Microwire electrodes had better signal-to-noise ratio; No significant effect of size on electrode performance	87
Cylindrical shank	Polyamide cylindrically shaped depth probes	N/A	Neuronal death minimal around probe; moderate cell death in neocortex 25 μm from probe	Weak to moderate FBR around shank	Reduction in signal-to-noise ratio over the course of 9 weeks; Stable MEA recording activity for several weeks	88
Floating MEAs	Silicon wafer dummy floating electrodes coated with hexamethyldisilazane, photoresist, and Parylene-C	N/A	N/A	More significant FBR when implanted in spinal cord compared to brain; microglial reactivity did not increase over time	N/A	89
Stiffness Modifications for MEAs
Flexible/soft MEAs	Parylene-C sinusoidal MEAs	N/A	Increase in neuronal cell density near probe	Significantly reduced astrocytic and microglial responses	N/A	92
	Ultraflexible nanoelectric thread	Seamless tissue integration	Normal astrocyte density and morphology; complete absence of neuronal degradation	Complete absence of glial scarring; no observable chronic tissue reaction	Persistently high signal-to-noise ratio; Stable recording performance for several months	93
	Ultrasoft MEAs composed of elastomers and conductive polymers	Reduced cell body distortion	Significantly higher neuronal cell density at 8 weeks compared to stiff implants	Significantly reduced FBR at 8 weeks	Successful acute nerve stimulation	95
	Soft polypyrrol MEAs	Good MEA-substrate adhesion	N/A	N/A	High conductivity and successful recording of electrocorticograph signals; rat ischiadic nerve stimulation achieved	96
Temporarily stiff MEAs
Stiff material coating	Flexible Parylene-C shank electrode with tapered profile; stiffened using applied dextran coating	Neuronal infiltration of dextran coat area following dissolution	No significant loss of neuronal cell density	Very limited glial scar tissue formation after 4 months	N/A	97a
	Flexible gold, Parylene-C insulated electrodes; stiffened using applied gelatin coating	N/A	N/A	N/A	Signal-to-noise ratio remained stable during 3-week period; MEA structure preserved during study period	98
Mechanical adaptivity	Poly(vinyl acetate)/tunicate cellulose nanocrystal nanocomposite MEAs	N/A	Significant neuronal cell loss initially, but neuronal cell recovery was seen over time 100 μm from implant	Significantly reduced FBR long-term at 2, 6, and 18 weeks	Stable electrochemical impedance spectra for 16 weeks	94b, 100
Stiff MEAs with surface modifications	Stiff glass capillary neural probes coated with soft PEG-DMA hydrogel	N/A	N/A	Significant reduction in glial scarring	N/A	102