Date of Award

Fall 2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular Science and Nanotechnology

First Advisor

David K. Mills

Abstract

Customized patient therapy has been a major research focus in recent years. There are two research fields that have made a significant contribution to realizing individualized-based treatment: targeted drug delivery and three-dimensional (3D) printing technology. With benefit from the advances in nanotechnology and biomaterial science, various drug delivery systems have been established to provide precise control of therapeutic agents release in time and space. The emergence of three-dimensional (3D) printing technology enables the fabrication of complicated structures that effectively mimic native tissues and makes it possible to print patient-specific implants. My dissertation research used a clay nanoparticle, halloysite, to develop a drug delivery system and 3D scaffold which may contribute to individualized-based treatment.

Halloysite nanotubes (HNTs) are naturally occurring tubular nanoparticles with a hollow lumen. They possess a high aspect ratio, thermal stability, and unique oppositely charged inner and outer surfaces. These inherent features enable them to be used as a bulk filler to improve the performance characteristics of many polymers. Besides, HNTs are biocompatible and have a demonstrated capacity to delivery growth factors, RNA, DNA and other chemical substances; therefore, HNTs have received extensive attention in the development of drug delivery systems. In this dissertation, HNTs were applied in the development of medical devices for bone disease remediation, tissue regeneration, and restoration of bone function.

Osteomyelitis is a bone infection and mainly caused by Staphylococcus aureus (S. aureus). Gentamicin is the antibiotic commonly used to against gram- negative and positive bacteria, which includes S. aureus. When gentamicin was loaded into HNTs and incorporated with chitosan, the hybrid chitosan/HNTs hydrogels provided a sustained drug release and successfully inhibited the growth of S. aureus. Simultaneously, the addition of HNTs improved chitosan mechanical properties.

Osteosarcoma is the most common cancer tumor occurring in bone tissue. Through surface modification, HNTs were conjugated with folic acid and fluorochrome (FITC). The bi-functionalized HNTs (bHNTs) were then doped with anticancer drugs, methotrexate (MTX). MTX-doped bHNTs showed a high drug loading efficiency and selectively targeted cancer cells. MTX-loaded bHNTs efficiently inhibited osteosarcoma proliferation without harm to normal type cells (pre-osteoblasts).

Osteoporosis is the most common bone disease as the bone formation fails to keep up with the bone resorption rate. Bone fractures happen as a result of long-term bone defection. Three dimensional printed scaffolds that support bone regeneration could be a viable alternative to bone grafting, which is limited by insufficient supplies and issued with infection. Metal-doped HNTs were combined with PLA and printed with a specific pore size and porosity design. After surface modification, 3D printed HNTs/PLA scaffolds encouraged cell adhesion and osteogenic differentiation. Furthermore, surface coating of gentamicin had a long stock life to inhibit bacterial growth and promoted osteogenesis.

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