Microphysiological systems (MPS) designed to study the complexities of the peripheral and central nervous systems have made marked improvements over the years and have allowed researchers to assess in two and three dimensions the functional interconnectivity of neuronal tissues. The recent generation of brain organoids has further propelled the field into the nascent recapitulation of structural, functional, and effective connectivities which are found within the native human nervous system. Herein, we will review advances in culture methodologies, focused especially on those of human tissues, which seek to bridge the gap from 2D cultures to hierarchical and defined 3D MPS with the end goal of developing a robust nervous system-on-a-chip platform. These advances have far-reaching implications within basic science, pharmaceutical development, and translational medicine disciplines.

Colorimetric detection of arboviruses and vector mosquito species. (A) Aptamer-gold nanoparticle conjugates, (B) mosquito salivary protein, (C) Zika envelope protein, (D) visible color change, (E) imbibed diagnostic and (F) diagnostic cards.

Morphological modification of gold nanoparticles to obtain a highly efficient paper based sensor for colorimetric detection of epinephrine (LOD – Limit of Detection).

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Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3 rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8 ±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag + controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNPblood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused~60% mortality in 3 rd instar larvae when larval food was absent, while CNPs yielded only~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag + needed to achieve comparable larvicidal activity (2.7 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development.

In this study, capillary alginate gel (Capgel TM), a collagen and alginate based self-assembling biomaterial, was used as a cellular scaffold for the treatment of ischemic, full-thickness dermal wounds in mice. Capgel TM was synthesized using copper sulfate to form the initial sol before rinsing and stabilizing the patent capillary structures with carbodiimide chemistry. This crosslinked hydrogel was then injected into ischemic, full-thickness dermal wounds and analyzed via histology after 7 and 10 days to assess wound contracture, granulation bed tissue and vascular structures. Capgel TM showed good resorbability and was well-invested with infiltrating host cells and vascular structures during and after resorption.

Microelectrode arrays (MEAs) have become important tools in high throughput assessment of neuronal activity. However, geometric and electrical constraints largely limit their ability to detect action potentials to the neuronal soma. Enhancing the resolution of these systems to detect axonal action potentials has proved both challenging and complex. In this study, we have bundled sensory axons from dorsal root ganglia through a capillary alginate gel (Capgel™) interfaced with an MEA and observed an enhanced ability to detect spontaneous axonal activity compared with two-dimensional cultures. Moreover, this arrangement facilitated the long-term monitoring of spontaneous activity from the same bundle of axons at a single electrode. Finally, using waveform analysis for cultures treated with the nociceptor agonist capsaicin, we were able to dissect action potentials from multiple axons on an individual electrode, suggesting that this model can reproduce the functional complexity associated with sensory fascicles in vivo. This novel three-dimensional functional model of the peripheral nerve can be used to study the functional complexities of peripheral neuropathies and nerve regeneration as well as being utilized in the development of novel therapeutics. KEYWORDS axonal action potential, capillary alginate gel, dorsal root ganglion, microelectrode array, threedimensional nerve model

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