Silk and PEG as means to stiffen a parylene probe for insertion in the brain: toward a double time-scale tool for local drug delivery

Abstract

The use of soft materials as substrate for neural probes aims at achieving better compliance with the surrounding neurons while maintaining minimal rejection. Many strategies have emerged to enable such probes to penetrate the cortex, among which the use of resorbable polymers. We performed several tests involving two resorbable polymers considered most promising: polyethylene glycol (PEG) and silk fibroin (SF) from Bombyx Mori silkworms. Our coating method provides a repeatable, uniform structure optimized for a stress-reduced insertion of a parylene-C neural probe. Standard compression tests as well as in vitro and in vivo insertion assessments show that both SF and PEG-coated probes are stiff enough to avoid the buckling effect during insertion in the cortex. However, with a buckling force of 300 mN and a mechanical holding in vitro of tens of minutes, we assess silk fibroin to be more reliable for practical handling. In vivo first try-outs in mouse brain showed neither buckling issues of the probe nor undesired alteration of the signal recording. Moreover, we evidenced two distinct time scales in the bioresorption of our polymer coatings: silk fibroin degrades itself in a matter of weeks and PEG dissolves itself within seconds in the presence of water. We then present a hybrid PEG and SF coating that could be used as a drug delivery system with different time scales to reduce both the acute and the chronic body reaction.

A Removable Insertion Shuttle for Ultraflexible Neural Probe Implantation with Stable Chronic Brain Electrophysiological Recording

“…However, the low stiffness of flexible neural probe makes it susceptible to bending and buckling during insertion into the brain. To deal with this dilemma, several delicate strategies have been developed to guide the insertion such as transient shuttles with dissolvable support materials such as silk, sugars, hydrogel or polyethylene glycol (PEG) as coatings, metal as rigid backbone layers for insertion, and removable shuttles with SU‐8 shanks or microneedles as temporary carriers. To remove the need of additional materials that may displace tissue in shuttle strategies, mechanically adaptive materials that change modulus on exposure to physiological conditions have been utilized as the probe substrates despite the potential biocompatibility issue.…”

Microfabricated Probes for Studying Brain Chemistry: A Review

“…Despite the potential benefit of soft implants, they are generally designed for primary use at the brain surface, or at depths up to a few millimeters. Otherwise, soft implants normally require the use of needle guide or stiff coating (such as polyethylene glycol (PEG) or biodegradable silk) for aiding tissue penetration and trajectory to deep brain tissue.…”

“…[102] D) Subcellular probef or dopamine detection madebyc ombination of assembly of carbon fiber and microfabricationo fp arylene insulator. [103] able silk [138,139] )f or aiding tissue penetration and trajectoryt o deep brain tissue.…”

NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording

“…A critical challenge to these and other very soft electrodes is insertion into the brain due to their fragility and lack of mechanical stiffness. Previous research has shown that compliant electrodes can be inserted using mechanical shuttles (22), stiffening agents (23,24), or syringes (14). However, standard shuttles for a planar array of the NeuroRoots would be hundreds of microns wide and cause significant damage on their own.…”