Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

Abstract

In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 mm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized by Nissl staining, Timm sulphide silver-staining, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) immunostaining, the slice cultures grown on chips did not differ from conventionally grown slice cultures. Neither were there any signs of astrogliosis or neurodegeneration around the upper recording part of the 47-mm-high platinum-tip electrodes. Slice cultures grown on a separate set of chips with platinum instead of silicon nitride surfaces also displayed normal MAP2 and GFAP immunostaining. The width of the GFAP-rich zone (glia limitans) at the bottom surface of the slice cultures was the same (|20 mm) in cultures grown on chips with silicon nitride and platinum surfaces and on conventional insert membranes. The slice cultures grown on chips maintained a normal, subfield differentiated susceptibility to the glutamate receptor agonist N-methyl-D-aspartate (NMDA) and the neurotoxin trimethyltin (TMT), as demonstrated by the cellular uptake of propidium iodide (PI), which was used as a reproducible and quantifiable marker for neuronal degeneration. We conclude that organotypic brain slice cultures can grow on silicon-based three-dimensional microelectrode arrays and develop normally with display of normal subfield differentiated susceptibilities to known excito-and neurotoxins. From this it is anticipated that the set-up, designed for recording of electrophysiological parameters, can be used for long-term studies of defined neuronal networks and provide valuable information on both normal, neurotoxicological and neuropathological conditions. Theme: Disorders of the nervous systemTopic: Neurotoxicity

Massively Parallel Recording of Unit and Local Field Potentials With Silicon-Based Electrodes

“…In chronic experiments, the tracks could be recognized by the tissue indent left by the shanks (Csicsvari et al 2003). No obvious tissue reaction was visible around the tracks, in support of a recent detailed report on the biocompatibility of silicon-based devices (Kristensen et al 2001).…”

Cell placement and guidance on substrates for neurochip interfaces

“…This is particularly important since dysfunction of synaptic connections is a common feature of neurodegenerative diseases. Spatially organized field potential recordings of electrical activity from synchronized populations of neurons in brain slices using multi-electrode arrays (MEAs), have provided a powerful tool for research in this area (Kristensen et al, 2001;Thiebaud et al, 1999). Similarly, MEAs have been used to record activity from brain cells grown randomly in culture (Gopal, 2003;Pancrazio et al, 2003).…”

The Rationale for Silicon Nitride Bearings in Orthopaedic Applications

“…55 Other potential biomedical applications of silicon nitride include drug-release devices, microelectromechanical systems (Bio-MEMS), and traumatic reconstructions of otorhinolaryngologic skeletal defects. [56][57][58][59] A cancellous-structured porous silicon nitride composite ceramic has been developed and is in commercial use as a spinal fusion implant; cylindrical implants have shown bone ingrowth rates similar to those reported for porous titanium, indicating that porous silicon nitride is an excellent substrate for implants designed for direct, biological skeletal fixation. 60 New bone forms even in the cortical region of the rabbit tibia, and around silicon nitride implants, suggesting that the material is osteoconductive, and promotes stable osseous fixation.…”