We recently introduced a series of stimuli-responsive, mechanically adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet become mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E' = ~5 GPa) than the neat polymer microprobes (E' = ~2 GPa) and can sustain higher loads (~12 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of insertion into cortical tissue. Further, we demonstrated the material's ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to eight weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially for other biomedical applications.

Intracortical microelectrodes (IME) are neural devices that initially were designed to function as neuroscience tools to enable researchers to understand the nervous system. Over the years, technology that aids interfacing with the nervous system has allowed the ability to treat patients with a wide range of neurological injuries and diseases. Despite the substantial success that has been demonstrated using IME in neural interface applications, these implants eventually fail due to loss of quality recording signals. Recent strategies to improve interfacing with the nervous system have been inspired by methods that mimic the native tissue. This review focusses on one strategy in particular, nano-architecture, a term we introduce that encompasses the approach of roughening the surface of the implant. Various nano-architecture approaches have been hypothesized to improve the biocompatibility of IMEs, enhance the recording quality, and increase the longevity of the implant. This review will begin by introducing IME technology and discuss the challenges facing the clinical deployment of IME technology. The biological inspiration of nano-architecture approaches will be explained as well as leading fabrication methods used to create nano-architecture and their limitations. A review of the effects of nano-architecture surfaces on neural cells will be examined, depicting the various cellular responses to these modified surfaces in both in vitro and pre-clinical models. The proposed mechanism elucidating the ability of nano-architectures to influence cellular phenotype will be considered. Finally, the frontiers of next generation nano-architecture IMEs will be identified, with perspective given on the future impact of this interfacing approach.

This paper reports the design, fabrication, and characterization of diamond-on-polymer microelectrode arrays. A “diamond-first” chemical release transfer process was implemented to integrate diamond electrodes, grown at temperatures >; 700 °C, on a temperature-sensitive polynorbornene-based (PNB) substrate, allowing for the advantageous neural interfacing properties of diamond to be utilized in a flexible device. Intracortical probes with two electrodes and peripheral nerve electrode arrays with ten electrodes ranging in area from 800 to 41 000 μm² were fabricated. Mechanical testing showed that the structures were flexible, with the composite structure having mechanical characteristics similar to bare PNB. Electrical testing confirmed that ohmic contacts were formed without a postanneal step and determined a diamond-on-polymer electrode impedance of ~ 1.5 MΩ at 1 kHz.

Mechanical, materials, and biological causes of intracortical probe failure have hampered their utility in basic science and clinical applications. By anticipating causes of failure, we can design a system that will prevent the known causes of failure. The neural probe design was centered around a bio-inspired, mechanically-softening polymer nanocomposite. The polymer nanocomposite was functionalized with recording microelectrodes using a microfabrication process designed for chemical and thermal process compatibility. A custom package based upon a ribbon cable, printed circuit board, and a 3D-printed housing was designed to enable connection to external electronics. Probes were implanted into the primary motor cortex of Sprague-Dawley rats for 16 weeks, during which regular recording and electrochemical impedance spectroscopy measurement sessions took place. The implanted mechanically-softening probes had stable electrochemical impedance spectra across the 16 weeks and single units were recorded out to 16 weeks. The demonstration of chronic neural recording with the mechanically-softening probe suggests that probe architecture, custom package, and general design strategy are appropriate for long-term studies in rodents.

Introduction: Intracortical microelectrodes (IME) are vital to properly functioning brain-computer interfacing (BCI). However, the recording electrodes have shown a steady decline in performance after implantation, mainly due to chronic inflammation. Compliant materials have been explored to decrease differential strain resulting in lower neural inflammation. We have previously developed a fabrication method for creating mechanically adaptive microfluidic probes made of a cellulose nanocrystal (CNC) polymer nanocomposite material that can become compliant after implantation. Here, we hypothesized that our device, would have a similar tissue response to the industry standard, allowing drug delivery therapeutics to improve neural inflammation in the future.Methods: RNA expression analysis was performed to determine the extent of neural inflammation and oxidative stress in response to the device compared to controls and to naïve shame tissue.Results: Results presented for both four- and eight-weeks post-implantations suggest that our device offers a promising platform technology that can be used to deliver therapeutic strategies to improve IME performance.