{"675068":{"#nid":"675068","#data":{"type":"event","title":"BioE PhD Defense Presentation- Michelle Quizon","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003ECommittee:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EAndr\u00e9s Garc\u00eda,\u0026nbsp;Ph.D.\u003C\/strong\u003E\u0026nbsp;(Advisor) (School of Mechanical Engineering, \u003Cem\u003EGeorgia Institute of Technology\u003C\/em\u003E)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EEdward Botchwey,\u0026nbsp;Ph.D.\u003C\/strong\u003E\u0026nbsp;(Department of Biomedical Engineering, \u003Cem\u003EGeorgia Institute of Technology and Emory University\u003C\/em\u003E)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ERebecca Levit, M.D.\u0026nbsp;\u003C\/strong\u003E(School of Medicine, \u003Cem\u003EEmory University\u003C\/em\u003E)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EEdward Phelps, Ph.D.\u003C\/strong\u003E\u0026nbsp;(Department of Biomedical Engineering, \u003Cem\u003EUniversity of Florida\u003C\/em\u003E)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EKrish Roy, Ph.D.\u003C\/strong\u003E\u0026nbsp;(Department of Biomedical Engineering, \u003Cem\u003EVanderbilt University\u003C\/em\u003E)\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ESynthetic hydrogels for islet vascularization and engraftment in the subcutaneous space\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EType 1 diabetes (T1D) is a chronic, debilitating disease\u0026nbsp;characterized by the autoimmune destruction of insulin-producing beta cells within pancreatic islets. The gold standard for T1D cell therapy is clinical islet transplantation (CIT), the infusion of islets through the hepatic portal vein. While CIT recipients demonstrate enhanced blood glucose control,\u0026nbsp;the procedure is limited to a marginal subset of T1D patients due to 1) the lack of donor islets and 2) the absolute immunosuppression required to overcome the inhospitable nature of the intrahepatic site. Indeed, an expected \u0026gt;60% loss of islets is expected within three days following transplantation. Thus, there is a significant need\u0026nbsp;to establish an alternative extrahepatic transplant site that supports islet engraftment.\u003C\/p\u003E\u003Cp\u003EThe subcutaneous space is an attractive extrahepatic transplant site for T1D cell therapy given its high clinical potential in terms of surgical accessibility, ease of monitoring, and convenience for replenishment and\/or retrieval of therapeutic cargo. However, the unmodified subcutaneous space lacks the necessary vascularization to preserve islets. An elegant, facile strategy to promote vascularization is the biomaterial-mediated delivery of proangiogenic factors such as vascular endothelial growth factor (VEGF). The objective\u003Cem\u003E\u0026nbsp;\u003C\/em\u003Eof my project was to engineer VEGF-delivering synthetic poly(ethylene glycol) hydrogels (VEGF-PEG) that promoted islet vascularization, engraftment, and function in the subcutaneous space. My central hypothesis\u0026nbsp;was that VEGF-PEG can be tuned to do so.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETo test my hypothesis, I completed three specific aims. In Aim 1, I employed an \u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;co-culture of rat islets, human umbilical vein endothelial cells, and human mesenchymal stromal cells to screen key hydrogel parameters \u2013 namely, polymer density, tethered VEGF concentration, and adhesive peptide type \u2013 for endothelial cell network formation and islet-network interactions. In Aim 2, I demonstrated that my engineered VEGF-PEG platform supported rat islet survival, engraftment, and function upon subcutaneous delivery in immunocompromised, diabetic mice. Importantly, VEGF-PEG achieved normoglycemia and maintained islet graft function in diabetic mice for 12 weeks, aligning in performance to a leading natural biomaterial platform (islet viability matrix). \u0026nbsp;In Aim 3, I established a large animal model to evaluate the vasculogenic capabilities of engineered biomaterials. In healthy, nondiabetic Yucatan miniature pigs (n = 5), I demonstrated that a VEGF-PEG coating induced vascularization and local perfusion in the porcine subcutaneous space without detrimental health effects. I then successfully delivered neonatal Yorkshire pig islets in VEGF-PEG to an immunosuppressed, nondiabetic Yucatan miniature pig.\u003C\/p\u003E\u003Cp\u003EMy work has resulted in an optimized synthetic hydrogel for islet vascularization, engraftment, and function in the subcutaneous space. My three-pronged, multi-model approach (\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003Eco-culture of cells - \u003Cem\u003Ein vivo\u003C\/em\u003E\u0026nbsp;studies in rodents - \u003Cem\u003Ein vivo\u0026nbsp;\u003C\/em\u003Estudies in pigs) \u0026nbsp;has provided a novel, logically translational strategy to engineer vasculogenic materials. This work provides a foundation for future studies in a translational, diabetic large animal model \u2013 recapitulating the human subcutaneous space more so than preclinical rodent models that comprise majority of the field.\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBioE PhD Defense Presentation- \u0026nbsp;\u0022Synthetic hydrogels for islet vascularization and engraftment in the subcutaneous space\u0022- Michelle Quizon\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"\u0022Synthetic hydrogels for islet vascularization and engraftment in the subcutaneous space\u0022"}],"uid":"27917","created_gmt":"2024-06-10 14:29:06","changed_gmt":"2024-06-10 14:29:06","author":"Laura Paige","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-06-17T10:00:00-04:00","event_time_end":"2024-06-17T12:00:00-04:00","event_time_end_last":"2024-06-17T12:00:00-04:00","gmt_time_start":"2024-06-17 14:00:00","gmt_time_end":"2024-06-17 16:00:00","gmt_time_end_last":"2024-06-17 16:00:00","rrule":null,"timezone":"America\/New_York"},"location":"CHOA Room EBB","extras":[],"groups":[{"id":"65448","name":"Bioengineering Graduate Program"}],"categories":[],"keywords":[{"id":"172056","name":"go-BioE"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}