Hypoxic-Ischemic Encephalopathy (HIE) in the brain is the leading cause of morbidity and mortality in neonates and can lead to irreparable tissue damage and cognition. Thus, investigating key mediators of the HI response to identify points of therapeutic intervention has significant clinical potential. Brain repair after HI requires highly coordinated injury responses mediated by cell-derived extracellular vesicles (EVs). Studies show that stem cell-derived EVs attenuate the injury response in ischemic models by releasing neuroprotective, neurogenic, and anti-inflammatory factors. In contrast to 2D cell cultures, we successfully isolated and characterized EVs from whole brain rat tissue (BEV) to study the therapeutic potential of endogenous EVs. We showed that BEVs decrease cytotoxicity in an ex vivo oxygen glucose deprivation (OGD) brain slice model of HI in a dose- and time-dependent manner. The minimum therapeutic dosage was determined to be 25 μg BEVs with a therapeutic application time window of 4–24 h post-injury. At this therapeutic dosage, BEV treatment increased anti-inflammatory cytokine expression. The morphology of microglia was also observed to shift from an amoeboid, inflammatory phenotype to a restorative, anti-inflammatory phenotype between 24–48 h of BEV exposure after OGD injury, indicating a shift in phenotype following BEV treatment. These results demonstrate the use of OWH brain slices to facilitate understanding of BEV activity and therapeutic potential in complex brain pathologies for treating neurological injury in neonates.

Electrostatic patterning has improved the performance of devices incorporating electrospun fibers in a wide variety of applications. However, the impact of process parameters on the final fiber pattern in these systems is rarely analyzed. Herein, a systematic analytical approach is developed to define quantitative metrics related to fiber patterning. Three‐dimensional patterned dielectric elastomer collectors are fabricated via solution‐casting polydimethylsiloxane with embedded carbon black or liquid metal droplets. Fiber patterning metrics are used to evaluate the effect of collector parameters such as insulating layer thickness, electrical ground surface area, and three‐dimensional pattern geometry. Dielectric layer parameters such as conductive material concentration and particle diameter are also investigated. Using this framework, the best‐performing collector is shown to improve selectivity 30‐fold, uniformity ninefold, reproducibility eightfold, and increase fiber volume by one order of magnitude. Furthermore, eutectic gallium indium liquid metal and scaled‐up pattern geometries demonstrate the tunability of this approach and broad applicability of systematic fiber pattern analysis. This rational approach to patterned fiber development can be applied to virtually any method or pattern to better understand the fiber patterning processes.

Electrospinning is a process for fabricating nonwoven fibrous materials of versatile composition and form that has shown enormous promise as medical wound dressings, tissue engineered scaffolds, and for pharmaceutical delivery. However, pharmaceutical application and clinical translation of electrospun fibers requires a scalable process to control mass deposition and uniformity in the finished materials. Here, we show that free-surface electrospinning using a stationary wire electrode can generate fiber materials with high productivity and controllable deposition to achieve uniform area density (basis weight) that is relevant for scalable pharmaceutical dosage form production. Using a production-scale instrument, we performed statistically designed optimization experiments to identify a combination of parameters that improved productivity up to 13 g/h. By combining this optimization with process controls for dynamic movement of the electrospinning substrate, we also demonstrate the production of uniform and high area density materials of 50–120 G per square meter. We verified our process by fabricating a triple drug solid dosage form at a high area target density (100 g/m2) that largely showed less than a 10% coefficient of variation in mass or drug content. The process developed here provides a general approach for optimizing different material compositions for high productivity and uniformity, and advances the use of free-surface electrospinning for manufacturing fiber-based biomedical materials.