Nanoscale neuro-integrative coatings for neural implants

Silicon microelectrode arrays (Si MEAs) have great potential in enabling chronic in vivo recording of neural activity, but this potential has been hampered by scar tissue formation at the site of implantation. In this study, we report the fabrication and characterization of nanoscale coatings that have the potential of enhancing the biocompatibility of Si electrodes. We use electrostatic layer-by-layer (LbL) assembly to prepare nanoscale bioactive coatings on silicon substrates. We use the response of chick cortical neurons to these coatings to assess potential improvement in biocompatibility in vitro. The coatings are built on oxide covered silicon wafers by alternating polycations, polyethyleneimine (PEI) or chitosan (CH), with polyanions, either gelatin or laminin (LN). We use quartz crystal microbalance (QCM) to characterize the coatings. Our analysis confirms that we achieved approximately 30-110 angstroms scale coatings via LbL assembly. In contrast to bare oxide covered silicon, coated substrates had significantly enhanced chick cortical neuron adhesion and differentiation, with multilayers of PEI-LN showing the greatest improvement. The multilayers of PEI-LN were stable for at least 7 days in physiological conditions, as determined by an enzyme-linked immunosorbent assay (ELISA). In addition, impedance spectroscopy confirmed that multilayers of PEI and LN did not increase the magnitude of impedance of Si MEAs at the biologically relevant frequency of 1 kHz. Our study demonstrates that electrostatic LbL assembly enables nanoscale bioactive coatings, and that PEI-LN multilayers significantly enhance cortical neuronal attachment and differentiation in vitro with no deleterious effects on impedance of the electrodes. Such well-controlled nanoscale coatings have the potential to significantly impact the compatibility and performance of Si MEAs in vivo.