A Materials Roadmap to Functional Neural Interface Design

Abstract

Advancement in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments, cures, and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology, to record from and modulate neurons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long-term material stability diminish the quality of interface overtime. Recent advances in functional materials have been aimed at engineering solutions for chronic neural interfaces. Yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have largely avoided being addressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multi-dimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients will be achievable. In this review, the interdependence of different electrode components are highlighted to demonstrate the current materials-based challenges facing the field of neural interface engineering.

Glial responses to implanted electrodes in the brain

“…Soft, nanoscale and bioactive materials have been incorporated into device design to produce electrode arrays with improved biointegration 157 . The broad strategies are to reduce the mechanical mismatch between device materials and brain tissue, reduce the footprint (and invasiveness) of the array, enhance surface porosity to mitigate immune responses, or create a biomimetic or bioactive coating that conceals the implant from the foreign-body response 157 .…”

“…Polymer blends of silicones and poly(3,4-ethylenedioxythiophene) are the softest reported materials to record extracellular units, with accompanied reductions in microglial attachment 162 . However, these materials introduce challenges for functional device design and minimally damaging deployment 157 .…”

“…Both device architecture and its material composition affect flexibility, since bending stiffness is determined by both the Young’s modulus ( E ) and the dimensions of the material 26,157,170 . Bending stiffness is proportional to Et 3 (where t is the thickness of a rectangular cross-section), meaning that reduced stiffness scales more rapidly with decreased device dimensions than reductions in modulus.…”

Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density

“…Additionally, various studies have demonstrated that electrical stimulation can cause diverse effects such as increases in hippocampal and thalamic volume, increases in blood vessel size and synaptic density, cortical dendrite growth, and changes in mRNA expression—some of which may influence short‐term local somatic and axonal response (Agnew et al, ; Baudry, Oliver, Creager, Wieraszko, & Lynch, ; Brownson, Little, Jarvis, & Salmons, ; Chakravarty et al, ; Cooperrider et al, ; Gall, Murray, & Isackson, ; Hirano, Becker, & Zimmerman, ; Morris, Feasey, ten Bruggencate, Herz, & Hollt, ; Pudenz, Bullara, Dru, & Talalla, ; Sankar et al, ; Veerakumar et al, ; Xia, Buja, Scarpulla, & McMillin, ; Xia et al, ). In chronic neuromodulation or neuroprosthetic applications, additional complexities arise from tissue changes in both the neuronal and non‐neuronal populations due to the implantation injury (glia, neurovasculature, immune cells) (Kolarcik et al, ; Kozai, Jaquins‐Gerstl, Vazquez, Michael, & Cui, ; Michelson et al, ; Salatino, Ludwig, Kozai, & Purcell, ; Wellman & Kozai, ), electrode material degradation (Alba, Du, Catt, Kozai, & Cui, ; Cogan, ; Cogan et al, ; Kozai et al, ; Wellman et al, ; Wilks et al, ), and plastic changes from long‐term electrical stimulation (Agnew et al, ; Baudry et al, ; Brownson et al, ; Chakravarty et al, ; Cooperrider et al, ; Gall et al, ; Hirano et al, ; Merrill et al, ; Morris et al, ; Pudenz et al, ; Sankar et al, ; Veerakumar et al, ; Xia et al, ). Future studies should be aimed at disentangling the complex network of dendrites, axons, and cell bodies of inhibitory and excitatory cells that may be present near the electrode in the brain (Overstreet et al, ).…”

The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair

“…The persistence of a degenerative foreign body response afflicts both biological tissue as well as the material interface, reducing the long-term recording quality of chronically implanted devices. Consequently, the design of neural interfaces becomes a multi-faceted approach and must take into consideration a wide array of design parameters to functionally integrate electrical materials with biological tissue [7]. Efforts to solve issues of performance reliability and variability by engineering solutions of one aspect of device design prove insufficient when faced with multiple overwhelmingly complex and interconnected modes of failure.…”