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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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Advisor:
Julia E. Babensee, PhD | School of Biomedical Engineering, Georgia Institute of Technology.
Committee:
Susan Thomas, PhD | School of Mechanical Engineering, Georgia Institute of Technology.
Stanislav Emelianov, PhD | School of Electrical & Computer Engineering, Georgia Institute of Technology.
OPTIMIZATION OF IL-10 INCORPORATION FOR DENDRITIC CELLS Embedded IN PEG-4MAL HYDROGELS.
Abstract
Over the recent decades, translational research in biomaterials and immunoengineering has been appreciated by science, which is corroborated by the development of novel advanced therapies to treat cancer, autoimmunity, and other immune-related pathologies. Dendritic cells (DCs) have been at the core center of pharmaceutical and biological therapeutics as vital mediator of the immune system leveraging on its function to bridge the innate and adaptive immune system. This thesis focuses on developing a biomaterial system to ameliorate autoimmunity. This biomaterial system is comprised of a poly (ethylene glycol)- 4 arms maleimide (PEG-4MAL) hydrogels conjugated with the immunosuppressive cytokine, interleukin, IL-10, which is injectable, in situ cross linkable and degradable system for localized delivery of immunosuppressive DCs. Studies conducted here aimed at optimizing the amount of IL-10 incorporated in hydrogel at 500ng concentration, which exhibited highest DC viability, immunosuppressive phenotype and protection against pro-inflammatory insult as compared to hydrogel-incorporated DCs at lower loading IL-10 amounts. Additionally, the studies addressed the optimization of degradability of the hydrogel to control the release rate of IL-10 from the gel, by varying the ratio of adhesive peptides: VPM (degradable) and DTT (non-degradable) peptide crosslinkers. The results obtained are promising and shall be significant for in vivo model optimization of immunosuppressive viability and functionality for incorporated DCs in cell delivery immunotherapy function.
Henceforth, it important to incorporate optimal loading amounts of IL-10 with hydrogels embedding DCs because this immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype which consequently enhances cell viability and optimizes the system’s immune modulatory functionality.
