Nano-Architectural Approaches for Improved Intracortical Interface Technologies

Abstract

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.

Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application

“…This secondary injury is a result of brain swelling, leading to a decreased brain perfusion and thus ischemia, which ultimately contributes to the observed brain damage and ultimate morbidity in some patients. The innate inflammatory response induced by injury is crucial to maintain homeostasis; however, if left unbridled into a chronic state, this leads to oxidative stress and glial scarring [ 5 , 6 ]. The glial scar tissue not only secretes inhibitory molecules (e.g., chondroitin sulphate proteoglycans (CSPGs) and myelin-associated glycoproteins), it further creates a mechanical barrier that hinders axonal regrowth [ 7 , 8 ].…”

“…Therefore, several approaches have been used for the design of nanoscale scaffolds for neurotherapies, and many prototypes are based on well-established knowledge of the brain extracellular matrix (ECM). The ECM has been described as an interwoven network of nanofibers embedded in a hydrated gel-like matrix [ 6 , 13 ] with the ECM cells (astrocytes, neurons, oligodendrocytes, and microglia) constituting the framework of the milieu at the nanometer scale (viz. proteinaceous collagen fibrils ranging between 50 and 200 nm and fibronectin fibrils of 2–3 nm thick and 60–70 nm long) [ 6 , 14 ] that facilitate interaction with the ECM [ 13 ].…”

“…The ECM has been described as an interwoven network of nanofibers embedded in a hydrated gel-like matrix [ 6 , 13 ] with the ECM cells (astrocytes, neurons, oligodendrocytes, and microglia) constituting the framework of the milieu at the nanometer scale (viz. proteinaceous collagen fibrils ranging between 50 and 200 nm and fibronectin fibrils of 2–3 nm thick and 60–70 nm long) [ 6 , 14 ] that facilitate interaction with the ECM [ 13 ]. Therefore, it follows logic to design biomimetic scaffolds with precise nanoscale features to provide pseudo-in vivo architectural cues to optimally restore cell-cell interactions for neural (brain) tissue engineering applications.…”

Comparing the effects of uncoated nanostructured surfaces on primary neurons and astrocytes

“…These events lead to the signal obstruction between neurons and electrodes during long‐term implantation, degrade the performance of the neural electrodes causing instability, and eventually, the failure of the implanted device. The main aims of implant development are to improve neuronal survival and unimpeded regeneration and extension of neurites, while preventing microglial and astrocyte activation by keeping them from attaching to the implanted surface [see (Adewole, Serruya, Wolf, & Cullen, ; Fernandez & Botella, ; Jorfi, Skousen, Weder, & Capadona, ; Kim et al, ) for review].…”

“…One of the recent strategies is the topographical modification of neural implant surfaces, as imitating the structure of the extracellular matrix (ECM) can influence the attachment and behavior of neural cells (Jeon, Simon Jr, & Kim, ; Kim et al, ). The micro−/nanostructure of the implant surface can have a selective effect on astrocytes and neurons, demonstrated previously both in vitro and in vivo (Berces et al, ; Moxon et al, ; Moxon, Hallman, Aslani, Kalkhoran, & Lelkes, ; Piret, Perez, & Prinz, ).…”