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dc.rights.licenseUsers may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.
dc.contributorHahn, Mariah
dc.contributorHurley, Jennifer
dc.contributorGilbert, Ryan
dc.contributorMunoz-Pinto, Dany
dc.contributorWan, Leo Q.
dc.contributor.authorErndt-Marino, Joshua Dean
dc.date.accessioned2021-11-03T08:59:33Z
dc.date.available2021-11-03T08:59:33Z
dc.date.created2018-07-27T14:56:54Z
dc.date.issued2018-05
dc.identifier.urihttps://hdl.handle.net/20.500.13015/2174
dc.descriptionMay 2018
dc.descriptionSchool of Engineering
dc.description.abstractOsteoarthritis (OA) is characterized by a slow progression of cartilage erosion driven in part by a cascade of inflammatory mediators produced from an activated synovium and the cartilage itself. Chondrocytes lose their capacity to maintain a healthy cartilage extracellular matrix as they transition from an anabolic, healthy phenotype to a catabolic, hypertrophic phenotype. Activated synovial macrophages contribute to the chondrocyte phenotype shift and subsequent cartilage degradation through the secretion of pro-inflammatory molecules. Currently, there is not a single effective disease modifying treatment that can intervene in this degradative cascade. The goal of this work is to develop an intra-articular (IA) injection treatment that targets these two aberrant cell phenotypes through depolarization of the cells’ transmembrane potential (Vmem). Increasing the extracellular potassium (K+) concentration is a simple way to depolarize Vmem. In theory, a K+-based IA solution would be inexpensive, widely available, easy-to-implement, and able to alleviate long-term storage concerns associated with other potential treatments such as stem cells or protein-based pharmaceuticals.
dc.description.abstractThis thesis focuses on initial, in vitro proof-of-concept studies designed to demonstrate the therapeutic potential a K+-based IA injection treatment for OA. Specifically, addition of K+ gluconate into culture media induces favorable changes in both osteoarthritic chondrocytes and interferon-gamma stimulated macrophages (M(IFN)). Furthermore, short-term stimulation (1 day) with K+ gluconate elicits prolonged beneficial responses in M(IFN) after 5 days despite the continued presence of IFN. The macrophage response noticed with K+ gluconate is not observed with either a clinically utilized IA injectable (methyl-prednisolone acetate - a corticosteroid) or a cell-based (human mesenchymal stem cell) injectable. Future work for this project will move towards in situ and in vivo studies.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectBiomedical engineering
dc.titleToward development of a potassium (K+)-based intra-articular injection for osteoarthritis treatment
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid178934
dc.digitool.pid178935
dc.digitool.pid178936
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreePhD
dc.relation.departmentDept. of Biomedical Engineering


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