Development of a solution-based process for hydroxyapatite and functionalised hydroxyapatite

Abstract

Hydroxyapatite coatings have long been established as a means of improving the osteointegration of metallic orthopaedic implants. Nonetheless there are both technical and commercial drawbacks associated with industrial coating techniques. Potential improvements such as adding therapeutic compounds highlight the need for new and innovative coating techniques. This thesis explores the use of metastable colloidal (particles between 1 and 1000nm in size) calcium and phosphate solutions that can lead to selective precipitation of insoluble hydroxyapatite mineral at a solution-surface interface. This process is intrinsically difficult to control and the introduction of careful process controls to all variables within this solution deposition system is needed to pave the way for industrial scale up of a novel laboratory-based system. Precise control and understanding of the process also allows for the investigation of the kinetics and mechanism of the deposition of hydroxyapatite on traditional and non-conventional surfaces. There is always an ongoing need to improve the osteointegration of orthopaedic implants beyond what hydroxyapatite alone can offer so that rejection and revision surgery can be avoided. There is growing need for enhanced antimicrobial performance and drug delivery properties of biomedical surfaces to improve success rates of operations. This issue is addressed herein via design and testing of a polymer patterning method for the inclusion of additional active ions to a hydroxyapatite coating. The work can be grouped into two core categories. 1. Understanding: this means that through experimentation, chemistry fundamentals, materials characterisation and data analysis an understanding of the molecular intricacies within a novel solution-deposition hydroxyapatite coating process is achieved. (Chapters 2, 3 & 4) 2. Functionalisation: investigation of the biological activity of a dopant and the design of experiments for a system which adds certain elements to an orthopaedic surface with a view to aiding patient outcomes. (Chapters 5 & 6) Chapter 1 provides a background literature review of hydroxyapatite and its use as an orthopaedic coating. Detailed here are the limitations and challenges surrounding traditional coating techniques and their narrow focus on titanium based metallic parts. Opportunities regarding the doping of hydroxyapatite with novel materials on novel surfaces are identified and analytically compared. Chapter 2 introduces the novel system of depositing hydroxyapatite using colloidal solutions of calcium and phosphates. The effect of solution concentration and deposition kinetics are explored and explained. A proposed chemical pathway for the nucleation and crystal growth of certain hydroxyapatite phases within solution is presented and confirmed to be accurate. Outlined are the optimum process settings of temperature, time, pH and concentration that produce repeatable hydroxyapatite films. Chapter 3 leverages the findings and the novel system presented in Chapter 2 to deposit an `ideal? hydroxyapatite film and investigate its attachment to bulk titanium parts. Detailed characterisation of the coating and the film?s growth mechanism is provided. Chapter 4 takes the findings of both Chapter 2 and Chapter 3 and applies the solution deposition process to non-bulk titanium parts such as silicon or silicon with 100 nm titanium films. Hydroxyapatite coating efficacy is shown to be dependent on substrate roughness, hydrophilicity and activation. Resulting data suggest that once hydroxyapatite seeds, it grows identically regardless of substrate. Chapter 5 chapter represents a standalone study of gallium nano-coatings and introduces the field of block copolymer patterning with a view to overcoming some of the known challenges of doping hydroxyapatite. Block copolymer patterns are used to generate novel orthopaedic coatings of gallium oxide on silicon and titanium thin films. Extensive characterisation of gallium nanodot coating and biological assay tests show that controlled release of gallium ions from coating improves osteointegration. The osteogenesis and osteoclastogenesis tests were conducted by collaborators Mimma Maggio and Carolina Martens of the Hoey group. Chapter 6 harnesses the findings of Chapter 5 and applies them to hydroxyapatite coatings formed using the parameters set out in Chapters 2 and 3. This ground-breaking work shows how a polymer pattern can be applied over a ceramic layer. Infiltration of the polymer layer with inorganic dopants of osteogenic and antimicrobial relevance acts as an innovative method of securing additive ions to hydroxyapatite. While elements such as gallium or zinc can be detected, it is fully proven to have no impact on the HA crystal structure or film properties. Chapter 7 outlines the central findings of this work and highlights the major achievements which have contributed to the field of biomaterials research. A suggestion of future work is also presented which would further advance the conclusions of each chapter.