Bioinspired micro- and nano-structured neural interfaces

Abstract

The development of a functional nervous system requires neurons to interact with and promptly respond to a wealth of biochemical, mechanical and topographical cues found in the neural extracellular matrix (ECM). Among these, ECM topographical cues have been found to strongly influence neuronal function and behavior. Here, we discuss how the blueprint of the architectural organization of the brain ECM has been tremendously useful as a source of inspiration to design biomimetic substrates to enhance neural interfaces and dictate neuronal behavior at the cell-material interface. In particular, we focus on different strategies to recapitulate cell-ECM and cell-cell interactions. In order to mimic cell-ECM interactions, we introduce roughness as a first approach to provide informative topographical biomimetic cues to neurons. We then examine 3D scaffolds and hydrogels, as softer 3D platforms for neural interfaces. Moreover, we will discuss how anisotropic features such as grooves and fibers, recapitulating both ECM fibrils and axonal tracts, may provide recognizable paths and tracks that neuron can follow as they develop and establish functional connections. Finally, we show how isotropic topographical cues, recapitulating shapes, and geometries of filopodia- and mushroom-like dendritic spines, have been instrumental to better reproduce neuron-neuron interactions for applications in bioelectronics and neural repair strategies. The high complexity of the brain architecture makes the quest for the fabrication of create more biologically relevant biomimetic architectures in continuous and fast development. Here, we discuss how recent advancements in two-photon polymerization (2PP) and remotely reconfigurable dynamic interfaces are paving the way towards to a new class of smart biointerfaces for in vitro applications spanning from neural tissue engineering as well as neural repair strategies.

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

“…[203,204] Here, it is instrumental to design electroactive elements, which would favor not only the mechanical stability at the cell-material interface but characterize the biorecognition mechanism often governed by the plasma membrane response and its curvature. [205] Electroactive elements can resemble typical electrogenic features [206] and functions [207] as in living tissue (i.e., neuronal tissue), as well as exploit multimodal sensing capabilities. [208] Here, the ability of the electroactive biomaterial to sense ions and electrons is fundamental for the monitoring of electrochemical processes, which govern cell-cell communication within the tissue.…”

Toward the Next Generation of Neural Iontronic Interfaces

“…Such materials range from lipid-bilayer-based interfaces, extra-cellular-matrix-emulating surfaces, ion-pumpmimicking organic electronics and neurotransmitter-releasing materials. [73,[82][83][84] These devices will be beneficial for the longterm integration of devices into neural tissue and more research is needed on the particular form of biomimetic designs that would work best.…”

Concealing Organic Neuromorphic Devices with Neuronal‐Inspired Supported Lipid Bilayers

“…[ 2 ] Here, the creation of neuronal‐like conductive materials has been exploited by patterning vertical structures to emulate dendritic spine as well as fabricating fiber‐based assembly, mirroring neurites and branching out architectures. [ 3 ] Moreover, to recapitulate neuron‐neuron communication and adhesion processes mediated by the plasma membrane, artificial bilayers have been also used as suitable in vitro cell culture platforms for neuronal cells. [ 4 , 5 , 6 , 7 , 8 ] Here, the lipid composition and charge can modulate the neuronal outgrowth and development inhibiting or supporting the neurites sprouting.…”