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

Miller, Ryan C.

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

Description

Title

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

Author(s)

Miller, Ryan C.

Issue Date

2023-04-26

Director of Research (if dissertation) or Advisor (if thesis)

• Kong, Hyunjoon
• Han, He-Sun

Doctoral Committee Chair(s)

Kong, Hyunjoon

Committee Member(s)

• Kraft, Mary
• Peters, Baron
• Gillette, Martha

Department of Study

Chemical & Biomolecular Engr

Discipline

Chemical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

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

Abstract

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.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Ryan Miller

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