Investigations of tethering induced injury response in brain tissue by intracortical implants through modeling and in vivo experiments.

摘要

One of the limitations of intracortical microelectrodes in chronic applications is their inability to transduce signals of interest for sustained periods of time. Of the many failure modes, the chronic tissue response (CTR) evoked by the continued presence of these sensors in the brain tissue is of particular interest to neural engineers. Thus mitigating this response is of the utmost importance in furthering the usage of these implants for chronic applications.; In this study, the effect of relative motion of implants with respect to brain tissue (micromotion) in inducing CTR was tested by (1) developing a finite-element model to simulate interfacial strain induced by micromotion and quantifying the injury response evoked by (2) implants in three tethering configurations and (3) stiff and flexible implant substrates through quantitative immunohistochemistry (IHC). Results from these experiments are detailed below. (1) A 3-D finite-element model of the probe-brain tissue microenvironment was developed and three candidate substrates were simulated. A tangential tethering force resulted in 94% reduction in strain value at the tip of the polyimide probe track in the tissue, whereas the simulated "soft" probe induced two orders of magnitude smaller values of strain compared to a simulated silicon probe. (2) Untethered implants caused significantly smaller neuronal loss than both conventionally tethered and flexibly tethered implants in the first 25 mum from the implant-tissue interface (32%, 56% and 54%, respectively) (p 0.05). Based on the evidence, the sustained presence of a transcranial interconnect attached to an implant is believed to be more important in determining the injury response than the interconnect flexibility in chronic intracortical implants. (3) "Rigid" (parylene) implants caused significantly smaller neuronal loss and smaller increase in non-neuronal cells than "flexible" (polydimethylsiloxane) implants. The apparent contradiction was explained by the hydrophobic nature and the resulting adsorption of proteins onto the PDMS substrate.; The results suggest that modulating mechanical stiffness of implant materials alone has limited effect on CTR and that a complex problem like this could be best addressed by a combination of techniques.