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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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BME Defense Presentation: Candice M. Hovell
Date and Time: June 29, 2017 @ 10am EST
Location: Marcus Nanotechnology Building, Room 1117
Advisors:
YongTae (Tony) Kim, PhD; Georgia Tech Mechanical Engineering
Lakeshia Taite, PhD; Texas A&M University Department of Veterinary Medicine
Gilda Barabino, PhD; Dean of Engineering City College of New York
Committee Members:
Brandon Dixon, PhD; Georgia Tech Mechanical Engineering
Edward Botchwey, PhD; Georgia Tech Biomedical Engineering
Hang Lu, PhD; Georgia Tech Chemical & Biomolecular Engineering
Maribel Vazquez, PhD; City College of New York, Biomedical Engineering
Title: Development of a Novel In Vitro Blood Brain Barrier Model for the Evaluation of Nanomedicines
In this work, we present a novel microfluidic lumen system of the BBB (MLS-BBB) for the evaluation of multifunctional nanomedicines engineered for the treatment of medulloblastoma. Our MLS-BBB is designed to co-culture human astrocytes (HA) and human brain vascular pericytes (HBVP) around a cylindrical lumen of human brain microvascular endothelial cells (HBMEC) within a 3D hydrogel system tuned to mimic the properties of brain extracellular matrix (ECM). Our MLS-BBB facilitates the administration of tunable shear rates to a lumen of endothelial cells in direct contact with supporting astrocyte and pericyte cells within a hydrogel system optimized to facilitate the appropriate culture of astrocytes, and is to our knowledge, the first model to do so. We employed high throughput qPCR techniques to simultaneously analyze expression of 85 BBB relevant endothelial specializations such as junctional proteins (ZO-1, Claudins, JAMs, etc.), specialized transporters (GLUT-1, CAT1, TfR, etc.) and drug resistant proteins (PgP, ABCC1, ABCC4, etc.). Our results indicate that our system provides a marked increase in physiological relevance relative to transwell culture systems. Our model was further validated through comparison to BBB spheroids, by examination of model response to perturbations of the optimized ECM composition, and examination of response to the administration of TNFα, an inflammatory cytokine. Our model is currently being employed in parallel with traditional transwell systems and ex vivo brain slice cultures in the preliminary evaluation of a novel nanomedicine designed for the treatment of sonic hedgehog driven (SSH) medulloblastoma to evaluate its functional utility in such studies. The ultimate goal of organ-on-a-chip model development is eventual adaptation by the community for preclinical assessment of novel drug compounds. While our MLS-BBB could be improved in several ways, including modification to a high throughout design, by combining comprehensive characterization with an assessment of functional utility relative to standard in vitro controls, we believe our work constitutes a significant step towards the realization of this goal.
