Date of Award

Fall 2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

David K. Mills

Abstract

Personalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound.

Chemotherapeutic or antibiotic enhanced 3D printing filaments were invented and designed to allow for the fabrication of antibiotic beads, drug eluting catheters, drains, stents, screws or any bioactive construct. Halloysite nanotubes (HNTs) were investigated as a modular platform and solely or in combinations were coated in metals including: iron for magnetic targeted delivery including hyperthermia, gold for laser targeted hyperthermia or barium as a contrast agent for visualization. The particles were test loaded with antibiotics or chemotherapeutics as well as coated in biocompatible coatings containing lipids or layered polyelectrolytes. Nanoparticles were added to 3D printing filaments or bone cements to test increases in strength, contrast or pore size.

3D print filaments and bioactive constructs that eluted gentamicin sulfate were tested using clinical microbiology lab standards and were shown to inhibit bacterial growth. 3D print filaments that eluted methotrexate were shown to inhibit proliferation of osteosarcoma cells and also provided a means for sustained drug release. Halloysite was successfully shown as a modular platform that could be highly customized for patient specific uses. Single coatings or combinations of magnetically susceptible iron coatings, gold coatings, drug loading of multiple bioactive compounds and biocompatible coatings were also developed. Bone cements with barium-coated particles were shown to have enhanced contrast.

The first ever ability to create and use bioactive 3D printing filaments on consumer printers was realized and HNTs were developed as proof of principle for multifunctional and real time customizable nanoparticle platforms. Nanoparticles as additives showed ways to modify established biomaterials or 3D printing filaments with enhanced features and properties.

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