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Reactive surface coatings reduce cerium in nanoscale ceria leading to more potent antioxidant behavior. 

Abstract Objective.The recording instability of neural implants due to neuroinflammation at the device-tissue interface is a primary roadblock to broad adoption of brain-machine interfaces. While a multiphasic immune response, marked by glial scaring, oxidative stress (OS), and neurodegeneration, is well-characterized, the independent contributions of systemic and local ‘innate’ immune responses are not well-understood. We aimed to understand and mitigate the isolated the innate neuroinflammatory response to devices.Approach.Three-dimensional primary neural cultures provide a unique environment for studying the drivers of neuroinflammation by decoupling the innate and systemic immune systems, while conserving an endogenous extracellular matrix and structural and functional network complexity. We created a three-dimensionalin vitromodel of the device-tissue interface by seeding primary cortical cells around microwires. Live imaging of both dye and Adeno-Associated Virus (AAV) - mediated functional, structural, and lipid peroxidation fluorescence was employed to characterize the neuroinflammatory response.Main results.Live imaging of microtissues over time revealed independent innate neuroinflammation, marked by increased OS, decreased neuronal density, and increased functional connectivity. We demonstrated the use of this model for therapeutic screening by directly applying drugs to neural tissue, bypassing low bioavailability through thein vivoblood brain barrier. As there is growing interest in long-acting antioxidant therapies, we tested efficacy of ‘perpetual’ antioxidant ceria nanoparticles, which reduced OS, increased neuronal density, and protected functional connectivity.Significance.Our three-dimensionalin vitromodel of the device-tissue interface exhibited symptoms of OS-mediated innate neuroinflammation, indicating a significant local immune response to devices. The dysregulation of functional connectivity of microcircuits surround implants suggests the presence of an observer effect, in which the process of recording neural activity may fundamentally change the neural signal. Finally, the demonstration of antioxidant ceria nanoparticle treatment exhibited substantial promise as a neuroprotective and anti-inflammatory treatment strategy. 

Abstract Millions of people a year receive magnetic resonance imaging (MRI) contrast agents for the diagnosis of conditions as diverse as fatty liver disease and cancer. Gadolinium chelates, which provide preferredT₁contrast, are the current standard but face an uncertain future due to increasing concerns about their nephrogenic toxicity as well as poor performance in high‐field MRI scanners. Gadolinium‐containing nanocrystals are interesting alternatives as they bypass the kidneys and can offer the possibility of both intracellular accumulation and active targeting. Nanocrystal contrast performance is notably limited, however, as their organic coatings block water from close interactions with surface Gadoliniums. Here, these steric barriers to water exchange are minimized through shape engineering of plate‐like nanocrystals that possess accessible Gadoliniums at their edges. Sulfonated surface polymers promote second‐sphere relaxation processes that contribute remarkable contrast even at the highest fields (r₁= 32.6 × 10⁻³mGd⁻¹s⁻¹at 9.4 T). These noncytotoxic materials release no detectable free Gadolinium even under mild acidic conditions. They preferentially accumulate in the liver of mice with a circulation half‐life 50% longer than commercial agents. These features allow theseT₁MRI contrast agents to be applied for the first time to the ex vivo detection of nonalcoholic fatty liver disease in mice.