Microfluidic-engineered N-acetylcysteine crystals for oxidative stress control and biologics manufacturing

The overproduction of reactive oxygen species (ROS) and the onset of oxidative stress in cells and tissue has been shown to have major implications in abnormal cell behavior and the pathogenesis of disease. Furthermore, in the field of regenerative medicine and biologics manufacturing, oxidative stress control is essential for the production of useful therapeutics. As such, antioxidant formulations are used to neutralize overproduced ROS. Polymer-directed crystallization of hydrophilic antioxidants has attracted attention as a way to control drug efficacy however limitations still exist with achieving extended release and minimal release variation. As result, ROS-homeostasis is rarely achieved. Herein, the goal of my thesis work is to develop an advanced antioxidant crystal system that can overcome these drug delivery constraints and control the oxidative environment in injured cells and tissues. Chapter 2 lays the foundational work where I detail the material design of hyaluronate-dopamine stabilization of N-acetylcysteine crystals with an emphasis of optimizing both drug–polymer and polymer–polymer interactions. Applications of this work are extended to addressing silver ion induced oxidative stress in cardiac muscle and daphnia magna. Chapter 3 addresses release variation concerns using drop-microfluidics to assemble highly monodisperse crystals while overcoming limitations of crystallization efficiency in micro-drops. Chapter 4 builds upon the drop microfluidic approach by encapsulating the engineered crystals in microgels in order to achieve sustained release over previously unreachable times for hydrophilic drug crystals. In both Chapters 3 and 4, the application of the crystals is to control the senescent state in mesenchymal stem cells to improve biologics manufacturing for regenerative medicine. Overall, the evolution of the antioxidant crystal design introduced in this work is broadly applicable to restoring ROS-homeostasis in cells and can be used as a tool to control cell fate.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Miller, Ryan C.

Contributors dc:contributor

• Kong, Hyunjoon
• Han, He-Sun
• Kraft, Mary
• Peters, Baron
• Gillette, Martha

• Antioxidant
• Senescence
• Mesenchymal Stem Cells
• Reactive Oxygen Species

Statement dc:rights

• Copyright 2023 Ryan Miller

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/120300

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F120300