Engineering Novel Nano-Structured 3D-Printed Titanium Implants for Optimized Osseointegration, Antibacterial Protection and Localized Drug Delivery Applications
Date
2021
Authors
Makar, Shaheer Guirguis Maher
Editors
Advisors
Losic, Dusan
Atkins, Gerald J.
Atkins, Gerald J.
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Thesis
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Abstract
Titanium (Ti) and its alloys have been used for decades as bone implants owing to their desirable biomechanical properties and corrosion resistance. However, they present many postoperative challenges in the body including inadequate osseointegration (e.g., poor attachment and differentiation, or overgrowth of bone cells), inflammation and infection. More than 5% of bone implants are rejected requiring repeated surgeries associated with increased patient suffering and high socioeconomic expense. Moreover, the requirements and surface properties of the implant are significantly determined according to the type of application and duration of use. Permanent or long-term implants are required for ongoing fixation (e.g., dental implants, hip and bone replacements), thus they should support bone cell attachment and differentiation on their surface (osseointegration) to improve mechanical stability. On the other hand, short-term implants used for temporal fracture fixing, especially in paediatrics, which are eventually removed from the body after serving their purpose, should not support osseointegration in order to facilitate their surgical removal. Studies have indicated that the implant surface, micro- and nano-scale topography, could play a vital role in directing implant bio-integration. At the same time, the surface topography could significantly affect bacterial attachment and biofilm formation on the implant surface. This thesis aims to engineer new and advanced Ti implants featuring multiple functions including controlled cell-implant interaction (i.e., enhancement or reduction), localized drug release and bactericidal activity to address the key challenges associated with implants. As a result, four specific aims are included; (i) nano-surface fabrication of nano-tubular arrays (TNTs) or nanopillars onto the surface of 3D-printed Ti implants to achieve desired combination of micro- and nano-rough surface properties, (ii) studying the drug loading capabilities of the fabricated implants using different therapeutic agents (e.g., anticancer and antibacterial agents), (iii) controlling the cell adhesion and growth on the surface of the implants xv to optimize bone cell attachment for either permanent or removable implants and (iv) enhancing the antibacterial properties of the fabricated implants. In order to address these aims, 3D-printed titanium implants were fabricated using additive manufacturing selective laser melting (SLM) technology (i.e., 3D-printing) followed by low cost, scalable surface nanoengineering manufacturing technologies of electrochemical anodization and hydrothermal process. As a result, unique implants surfaces featuring hierarchical micro-nano structures were generated covered with either TNTs or nanopillars. The fabrication and physicochemical characterization of the fabricated implants were assessed using multiple techniques such as scanning electron microscope, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction spectroscopy (XRD) and water contact angle (WCA). Moreover, bone cell responses, drug delivery properties and antibacterial activity of fabricated implants were assessed in-vitro. Results described herein confirmed the successful fabrication of surface nanostructures (i.e., TNTs and nanopillars). The drug loading and release of anticancer (doxorubicin and Apo2L/TRAIL) and antibacterial (gallium ions) agents were successfully demonstrated. At the same time, the antibacterial activity of TNTs and nanopillars was verified against two bacterial strains that commonly cause bone infections; Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the control of bone cell growth over the implant surface was successfully demonstrated by adjusting the surface nano topography of the implants. The research studies completed in this thesis combine fundamental understanding and application of knowledge of the surface, structural and chemical characteristics of Ti implant surfaces. These findings will facilitate the engineering of the next generations of advanced bone implants that will open the door to replace conventional implant manufacturing technology.
School/Discipline
School of Chemical Engineering and Advanced Materials
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering and Advanced Materials, 2022
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