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Creators/Authors contains: "Verbridge, Scott_S"

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  1. Abstract Glioblastoma (GBM), characterized by high infiltrative capacity, is the most common and deadly type of primary brain tumor in adults. GBM cells, including therapy‐resistant glioblastoma stem‐like cells (GSCs), invade the healthy brain parenchyma to form secondary tumors even after patients undergo surgical resection and chemoradiotherapy. New techniques are therefore urgently needed to eradicate these residual tumor cells. A thiol‐Michael addition injectable hydrogel for compatibility with GBM therapy is previously characterized and optimized. This study aims to develop the hydrogel further to capture GBM/GSCs through CXCL12‐mediated chemotaxis. The release kinetics of hydrogel payloads are investigated, migration and invasion assays in response to chemoattractants are performed, and the GBM‐hydrogel interactions in vitro are studied. With a novel dual‐layer hydrogel platform, it is demonstrated that CXCL12 released from the synthetic hydrogel can induce the migration of U251 GBM cells and GSCs from the extracellular matrix microenvironment and promote invasion into the synthetic hydrogel via amoeboid migration. The survival of GBM cells entrapped deep into the synthetic hydrogel is limited, while live cells near the surface reinforce the hydrogel through fibronectin deposition. This synthetic hydrogel, therefore, demonstrates a promising method to attract and capture migratory GBM cells and GSCs responsive to CXCL12 chemotaxis. 
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  2. Abstract Electroresponsive hydrogels possess a conducting material component and respond to electric stimulation through reversible absorption and expulsion of water. The high level of hydration, soft elastomeric compliance, biocompatibility, and enhanced electrochemical properties render these hydrogels suitable for implantation in the brain to enhance the transmission of neural electric signals and ion transport. This review provides an overview of critical electroresponsive hydrogel properties for augmenting electric stimulation in the brain. A background on electric stimulation in the brain through electroresponsive hydrogels is provided. Common conducting materials and general techniques to integrate them into hydrogels are briefly discussed. This review focuses on and summarizes advances in electric stimulation of electroconductive hydrogels for therapeutic applications in the brain, such as for controlling delivery of drugs, directing neural stem cell differentiation and neurogenesis, improving neural biosensor capabilities, and enhancing neural electrode‐tissue interfaces. The key challenges in each of these applications are discussed and recommendations for future research are also provided. 
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  3. Abstract Cancer stem cells (CSCs) are aggressive subpopulations with increased stem‐like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers. Antigen‐based sorting of CSCs usually requires staining with multiple markers, making the experiments complicated, expensive, and sometimes unreliable. Here, we study the feasibility of using dielectrophoresis (DEP) for isolation of glioblastoma cells with increased stemness. We culture a glioblastoma cell line in the form of neurospheres as an in vitro model for glioblastoma stem cells. We demonstrate that spheroid forming cells have higher expression of stem cell marker, nestin. Next, we show that dielectric properties of neurospheres change as a result of changing culture conditions. Our results indicate that spheroid forming cells need higher voltages to experience the same DEP force magnitude compared to normal monolayer cultures of glioblastoma cell line. This study confirms the possibility of using DEP to isolate glioblastoma stem cells. 
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