Defense Date

10-31-2023

Graduation Date

Fall 12-15-2023

Availability

One-year Embargo

Submission Type

thesis

Degree Name

MS

Department

Biomedical Engineering

School

School of Science and Engineering

Committee Chair

Jelena M. Janjic

Committee Member

Kimberly F. Williams

Committee Member

John Viator

Committee Member

Vijay S. Gorantla

Keywords

Perfluorocarbon, Nanoemulsions, Large Scale Manufacturing, Preservation, VCA, Microfluidization, Near Infrared Fluorescence, NIRF

Abstract

Over 100,000 Americans are currently waiting for a life – saving organ transplant, yet 17 patients die daily waiting for a transplant they will never receive [1]. Preservation of organs is an area that has seen innovation throughout the years and can improve rates of transplantation, yet vascularized composite allotransplantation preservation has not followed suit [2]. Current standard of care is use of electrolyte solutions such as Histidine – Tryptophan – Ketoglutarate (HTK) or University of Wisconsin (UW) Solution, yet these perfusates lack an oxygen carrying component [3]. Hemoglobin – based oxygen carriers (HBOCs) have been investigated yet present issues with lack of NO scavenging, leading to mass cell death and graft failure [4]. Thus, development of a novel perfusate that delivers oxygen must be done. Perfluorocarbons (PFCs) have been investigated due to a linear relationship in oxygen loading and oxygen partial pressure due to the high polarity of the characteristic C – F bond [5]. Manufacturing of PFC-NEs can be performed in a number of different ways, yet microfluidization has yielded highly reproducible results at desired sizes [6].

In this project, I present the large – scale manufacturing methodology of fluorescently labeled perfluorocarbon nanoemulsions as novel oxygen carriers to enhance organ preservation. At the large – scale, perfluorocarbon nanoemulsions have shown long – term stability and limited batch-to-batch variability. Furthermore, perfluorocarbon nanoemulsions have shown colloidal and fluorescence stability before and after oxygenation, allowing for tracking of nanoemulsions throughout the vasculature during perfusion. Integrity of the nanoemulsions has also been maintained upon perfusion through human limbs. Confirmation has been performed by in vitro characterization of perfused PFC-NE, real – time image processing of PFC-NE perfusion throughout VCA, and real – time oxygen monitoring throughout the limbs.

Language

English

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