CITRATE-BASED BIOMATERIALS FOR NERVE TISSUE ENGINEERING AND BRAIN DRUG DELIVERY

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Author:
Kim, Gloria Bora
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
October 05, 2017
Committee Members:
  • Jian Yang, Dissertation Advisor
  • Cheng Dong, Committee Chair
  • Jian Yang, Committee Member
  • William O Hancock, Committee Member
  • Kevin Douglas Alloway, Outside Member
Keywords:
  • citric acid
  • biomaterials
  • nerve tissue engineering
  • brain cancer
  • drug delivery
Abstract:
Citric acid-derived biomaterials have recently become an intense focus of research in the search of new functional biomaterials for solving pressing medical problems. Citric acid, a well-known intermediate in the Krebs cycle, is a multifunctional, biocompatible, readily available, and inexpensive cornerstone monomer used in designing various classes of citrate-based biomaterials. In addition to the convenient citrate chemistry for the syntheses of a number of versatile polymers that may be elastomeric or mechanically strong and tough, injectable and photocrosslinkable, fluorescent and MRI detectable, and/or tissue adhesive, citric acid also presents inherent anti-bacterial and anti-clotting characteristics, which make citrate-based biomaterials ideal for a number of medical applications. This doctoral dissertation aims to explore the design of citric acid-based biomaterials for the drug delivery and nerve tissue engineering applications. In Chapter 2, cross-linked urethane-doped polyesters (CUPEs), previously developed in Yang’s lab by doping urethane bonds in the poly (diol citrate) polyester network, have been utilized to develop folic acid-incorporated CUPE nerve guidance conduits in order to enhance functional recovery in peripheral nerve injuries. In addition, the neuroprotective roles of folic acid on glial cells and neurons are investigated as an attempt to understand the clinical benefits of folic acid previously reported in the neural development and repair. In Chapter 3, aliphatic biodegradable photoluminescent polymers, also known as BPLPs and developed in Yang’s lab, were used to build a polymeric nanoparticle drug delivery system for brain cancer. More importantly, immune cells were implemented in the proposed drug delivery system as active and living delivery vehicles to transport the nanoparticles more effectively to the brain tumor. In Chapter 4, traction force microscopy was used to measure the traction force produced during the transmigration of immune cell-mediated drug delivery system developed in Chapter 3 as an attempt to understand the transmigration mechanism of the immune cell-mediated drug delivery system. Chapter 5 summarizes this dissertation briefly and presents future perspectives and potential applications that have not yet studied in this dissertation.