Characterization of the Neuroinflammatory Response to Thiol-ene Shape Memory Polymer Coated Intracortical Microelectrodes

Abstract

Thiol-ene based shape memory polymers (SMPs) have been developed for use as intracortical microelectrode substrates. The unique chemistry provides precise control over the mechanical and thermal glass-transition properties. As a result, SMP substrates are stiff at room temperature, allowing for insertion into the brain without buckling and subsequently soften in response to body temperatures, reducing the mechanical mismatch between device and tissue. Since the surface chemistry of the materials can contribute significantly to the ultimate biocompatibility, as a first step in the characterization of our SMPs, we sought to isolate the biological response to the implanted material surface without regards to the softening mechanics. To accomplish this, we tightly controlled for bulk stiffness by comparing bare silicon ‘dummy’ devices to thickness-matched silicon devices dip-coated with SMP. The neuroinflammatory response was evaluated after devices were implanted in the rat cortex for 2 or 16 weeks. We observed no differences in the markers tested at either time point, except that astrocytic scarring was significantly reduced for the dip-coated implants at 16 weeks. The surface properties of non-softening thiol-ene SMP substrates appeared to be equally-tolerated and just as suitable as silicon for neural implant substrates for applications such as intracortical microelectrodes, laying the groundwork for future softer devices to improve upon the prototype device performance presented here.

A softening laminar electrode for recording single unit activity from the rat hippocampus

“…SMP-coatings were at least as well tolerated as bare stainless steel 24 . In vivo neuronal loss and astrocyte activation were found comparable to that previously reported for silicon probes 22,23 .…”

An Injectable Neural Stimulation Electrode Made from an In‐Body Curing Polymer/Metal Composite

“…Over the past decade, there has been a renewed interest in the use of thin films and other “soft” electrode materials to create high‐channel, yet low geometric area electrodes with a Young's modulus closer to native tissue to minimize initial surgical trauma and the chronic immune response . These electrode development strategies include the use of PDMS substrates with conductive traces and electrode contacts to develop stretchable multicontact electrode arrays for stimulation and recording .…”

“…These electrode development strategies include the use of PDMS substrates with conductive traces and electrode contacts to develop stretchable multicontact electrode arrays for stimulation and recording . Additionally, shape memory polymer (SMP) or other “shuttles” have been used to create a stiff carrier to facilitate implantation of electrodes into the brain, yet leave a soft electrode chronically to minimize the immune response of tissue . Similarly, the Charles Lieber group has demonstrated that a ultraflexible open mesh electrode array can be injected into the rodent brain via syringe and minimize the chronic immune response, enabling high‐quality chronic recordings for periods of at least 12 weeks .…”

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes

“…Biological and non-biological electrode modifications, especially through the surface coating of substrates and electrode sites, are the most commonly used strategies to improve interfacial mechanical mismatch (Aregueta-Robles et al, 2014). Advances in fabrication approaches for integrating conductive polymers (Kim et al, 2018), shape-memory polymers (Shoffstall et al, 2018a), hydrogels (Crompton et al, 2007; Frampton et al, 2007) and carbon nanotubes (Baranauskas et al, 2011; Bareket-Keren and Hanein, 2012) onto complex electrode structures, provide not only a chronically stable neural interface, but also an improvement in the electrode performance. The reduced surface area combined with low impedance and sensitivity provided by such materials make them suitable for either stimulation and recording applications (Vitale et al, 2015; Du et al, 2017; Pancrazio et al, 2017; Wang et al, 2019).…”