Developing unique nanoporous titanate structures for biomedical applications: mechanisms, conversion and substitution

Titanate structures have been of interest in many sectors, including healthcare, due to their ease of manufacture (low processing temperature and simplistic equipment), ion exchange potential to produce multifunctional (bioactive and antibacterial) surfaces, as well as their nanoporosity. However, their use has been limited to only Ti-containing materials due to the specific wet chemical methodology employed. The work presented in this thesis demonstrates one of the first studies to generate gallium-doped titanate structures as a multifunctional surface, specifically to assess their cytocompatibility and antibacterial potential for biomedical applications. Successive wet chemical (5 M NaOH; 60 oC; 24 h), ion exchange (4 mM Ga(NO3)3; 60 oC; 24 h), and heat treatment (700 oC; 1 h) stages were employed on Cp-Ti surfaces. Gallium was shown to be fully incorporated (ca. 9 at.%) into the nanoporous titanate structure, and completely replaced sodium (initial Na content ca. 3 at.%). The heat treatment stage crystallised the amorphous titanate layer, which increased the stability and reduced the maximum level of Ga3+ released (ca. 2.76 vs. 0.68 ppm for pre- and post-heat treated gallium titanate samples, respectively) into DMEM over 7 d. Finally, the heat-treated gallium titanate samples were shown to be cytocompatible, compared to the non-heat-treated samples, which demonstrated a significant (p < 0.0001) reduction compared to the TCP control. Unfortunately, neither gallium titanate samples exhibited robust antibacterial properties against S. aureus. The applicability of titanate structures was furthered in this thesis through the optimisation and characterisation of novel wet chemical (5 M NaOH; 60 oC; 24 h) titanate-converted Ti thin films deposited via DC magnetron sputtering. The films produced were deposited onto 316L SS to function as thin coatings for orthopaedic applications. This was in lieu of the ‘gold standard’ plasma sprayed hydroxyapatite (HA) coatings, due to their inherent shortfalls such as residual internal stresses and long-term delamination. An understanding of the titanate growth mechanism through thickness and oxygen variations was also detailed. Tailorable coating properties (structural, morphological, etc.) were achieved via modification of the sputtering parameters used (target power, substrate biasing, and in situ substrate heating). Graded coating structures from columnar (Tc for the α-Ti (002) plane = 3.39) to more equiaxed (Tc(002) = 1.54) coatings were produced, with their influence on titanate formation being investigated. Equiaxed coatings generated the thickest titanate structures (ca. 1.63 vs. 1.12 μm for columnar grown films) due to a reduction in oblique angle crystal growth because of the decreased surface roughness (Ra: ca. 32.6 vs. 26 nm). This was contrary to the hypothesis that more columnar structures would allow greater NaOH penetration, and hence further conversion. It was also found the titanate structures formed even on 50 nm thick Ti films, as well as oxygen limiting the titanate formation mechanism. Finally, sodium and calcium titanate-converted thin (ca. 500 nm) Ti coatings (both columnar and equiaxed) were applied to Mg substrates to tailor its corrosion resistance for biomedical applications. The columnar calcium titanate coatings performed the best of all the coatings tested compared to Mg in terms of their corrosion resistance (Ecorr = ca. -1.33 vs. -1.49 V; icorr = ca. 0.06 vs. 0.31 mA.cm-2, respectively). The novel method outlined in this thesis has demonstrated consistent production of tailorable nanoporous titanate structures on non-Ti containing materials. Furthermore, the produced titanate structures enabled ion substitution of Ca ions, which have previously only been achieved in titanate structures produced on Ti substrates. The results detailed not only enhances the understanding of the titanate growth mechanism, but also demonstrates the broad applications enabled through this platform technology

Generation and characterisation of gallium titanate surfaces through hydrothermal ion-exchange processes

Infection negation and biofilm prevention are necessary developments needed for implant materials. Furthermore, an increase in publications regarding gallium (Ga) as an antimicrobial ion has resulted in bacterial-inhibitory surfaces incorporating gallium as opposed to silver (Ag). The authors present the production of novel gallium titanate surfaces through hydrothermal ion-exchange reactions. Commercially-pure Ti (S0: Cp-Ti) was initially suspended in NaOH solutions to obtain sodium titanate (S1: Na2TiO3) layers ca. 0.5–1 μm in depth (2.4 at.% Na). Subsequent suspension in Ga(NO3)3 (S2: Ga2(TiO3)3), and post-heat-treatment at 700 °C (S3: Ga2(TiO3)3-HT), generated gallium titanate layers (9.4 and 4.1 at.% Ga, respectively). For the first time, RHEED analysis of gallium titanate layers was conducted and demonstrated titanate formation. Degradation studies in DMEM showed S2: Ga2(TiO3)3 released more Ga compared to S3: Ga2(TiO3)3-HT (2.76 vs. 0.68 ppm) over 168 h. Furthermore, deposition of Ca/P in a Ca:P ratio of 1.71 and 1.34, on S2: Ga2(TiO3)3 and S3: Ga2(TiO3)3-HT, respectively, over 168 h was seen. However, the study failed to replicate the antimicrobial effect presented by Yamaguchi who utilised A. baumannii, compared to S. aureus used presently. The authors feel a full antimicrobial study is required to assess gallium titanate as a candidate antimicrobial surface

Stoichiometry and annealing condition on hydrogen capacity of TiCr2-x AB2 alloys

This study presents the effect of stoichiometry and annealing condition on Ti–Cr AB2-type hydrogen storage alloys. Prior to annealing the majority phase of the as-cast alloys was the C14 Laves phase, with separate Ti and Cr phases. Annealing treatment (1273 K/14 d) led to a transition from C14 to C15 Laves phase structure. Both C14 (as-cast) and C15 (annealed) cell size increased with Ti content, up to a ratio (Cr/Ti) of 1.6, due to B-site Ti substitution in the lattice up to a limit. Pressure composition isotherm (PCI) measurements demonstrated alloys containing a greater Ti content had a better maximum hydrogen storage capacity (1.5 vs. 1.03 wt%) and lower plateau pressure (9.4 vs. 15.8 bar) at 253 K. Annealing resulted in a lower storage capacity (1.05 vs. 1.49 wt%), greater plateau pressure (ca. 30 bar) and flatter plateau slope (25 % reduction in plateau slope). Reduction in hydrogen storage capacity of annealed alloys could be due to diffusion of residual Cr in the alloy into the C15 Laves phase during the annealing process, thereby changing the local composition as confirmed through X-ray diffraction (XRD)

Developing alkaline titanate surfaces for medical applications

Improving the surface of medical implants by plasma spraying of a hydroxyapatite coating can be of critical importance to their longevity and the patient’s convalescence. However, residual stresses, cracking, undesired crystallisation and delamination of the coating compromise the implants lifetime. A promising alternative surface application is an alkali-chemical treatment to generate bioactive surfaces, such as sodium and calcium titanate and their derivatives. Such surfaces obviate the need for high temperatures and resulting micro-crack formation and potentially improve the bioactive and bone integration properties through their nanoporous structures. Also, metallic ions such as silver, gallium and copper can be substituted into the titanate structure with the potential to reduce or eliminate the infections. This review examines the formation and mechanisms of bioactive/antibacterial alkaline titanate surfaces, their successes and limitations, and explores the future development of implant interfaces via multifunctional titanate surfaces on Ti-based alloys and on alternative substrate materials

Thermal and crystallization kinetics of yttrium-doped phosphate-based glasses

© 2019 The American Ceramic Society and Wiley Periodicals, Inc Yttrium-doped glasses have been utilized for biomedical applications such as radiotherapy, especially for liver cancer treatment. In this paper, the crystallization behavior of phosphate-based glasses doped with yttrium (in the system 45P2O5–(30 − x) Na2O–25CaO–xY2O3—where x = 0, 1, 3 and 5) have been investigated via Differential Scanning Calorimetry (DSC) using nonisothermal technique at different heating rates (5°C, 10°C, 15°C and 20°C/min). The glass compositions were characterized via EDX, XRD, Density and Molar volume analysis. The Moynihan and Kissinger methods were used for the determination of glass transition activation energy (Eg) which decreased from 192 to 118 kJ/mol (Moynihan) and 183 to 113 kJ/mol (Kissinger) with increasing yttrium oxide content. Incorporation of 0 to 5 mol% Y2O3 revealed an approximate decrease of 71 kJ/mol (Ozawa and Augis) for onset crystallization (Ex) and 26 kJ/mol (Kissinger) for crystallization peak activation energies (Ec). Avrami index (n) value analyzed via Matusita–Sakka equation suggested a one-dimensional crystal growth for the glasses investigated. SEM analysis explored the crystalline morphologies and revealed one-dimensional needle-like crystals. Overall, it was found that these glass formulations remained amorphous with up to 5 mol% Y2O3 addition with further increases in Y2O3 content resulting in significant crystallization

Developing highly nanoporous titanate structures via wet chemical conversion of DC magnetron sputtered titanium thin films

© 2020 The Authors Titanate structures have been widely investigated as biomedical component surfaces due to their bioactive, osteoinductive and antibacterial properties. However, these surfaces are limited to Ti and its alloys, due to the nature of the chemical conversion employed. The authors present a new method for generating nanoporous titanate structures on alternative biomaterial surfaces, such as other metals/alloys, ceramics and polymers, to produce bioactive and/or antibacterial properties in a simple yet effective way. Wet chemical (NaOH; 5 M; 60 °C; 24 h) conversion of DC magnetron sputtered Ti surfaces on 316L stainless steel were investigated to explore effects of microstructure on sodium titanate conversion. It was found that the more equiaxed thin films (B/300) generated the thickest titanate structures (ca. 1.6 μm), which disagreed with the proposed hypothesis of columnar structures allowing greater NaOH ingress. All film parameters tested ultimately generated titanate structures, as confirmed via EDX, SEM, XPS, XRD, FTIR and Raman analyses. Additionally, the more columnar structures (NB/NH & B/NH) had a greater quantity of Na (ca. 26 at.%) in the top portion of the films, as confirmed via XPS, however, on average the Na content was consistent across the films (ca. 5–9 at.%). Film adhesion for the more columnar structures (ca. 42 MPa), even on polished substrates, were close to that of the FDA requirement for plasma-sprayed HA coatings (ca. 50 MPa). This study demonstrates the potential of these surfaces to be applied onto a wide variety of material types, even polymeric materials, due to the lower processing temperatures utilised, with the vision to generate bioactive and/or antibacterial properties on a plethora of bioinert materials

Production of High Silicon-Doped Hydroxyapatite Thin Film Coatings via Magnetron Sputtering: Deposition, Characterisation, and In Vitro Biocompatibility

In recent years, it has been found that small weight percent additions of silicon to HA can be used to enhance the initial response between bone tissue and HA. A large amount of research has been concerned with bulk materials, however, only recently has the attention moved to the use of these doped materials as coatings. This paper focusses on the development of a co-RF and pulsed DC magnetron sputtering methodology to produce a high percentage Si containing HA (SiHA) thin films (from1.8 to 13.4 wt. %; one of the highest recorded in the literature to date). As deposited thin films were found to be amorphous, but crystallised at different annealing temperatures employed, dependent on silicon content, which also lowered surface energy profiles destabilising the films. X-ray photoelectron spectroscopy (XPS) was used to explore the structure of silicon within the films which were found to be in a polymeric (SiO2; Q4) state. However, after annealing, the films transformed to a SiO44- Q0, state, indicating that silicon had substituted into the HA lattice at higher concentrations than previously reported. A loss of hydroxyl groups and the maintenance of a single-phase HA crystal structure further provided evidence for silicon substitution. Furthermore, a human osteoblast cell (HOB) model was used to explore the in vitro cellular response. The cells appeared to prefer the HA surfaces compared to SiHA surfaces, which was thought to be due to the higher solubility of SiHA surfaces inhibiting protein mediated cell attachment. The extent of this effect was found to be dependent on film crystallinity and silicon content

Self-assembled titanium-based macrostructures with hierarchical (macro-, micro-, and nano) porosities : a fundamental study

This study details the novel self-assembly of sodium titanate converted Ti-based microspheres into hierarchical porous 3D constructs, with macro-, micro-, and nanoporosity, for the first time. Ti6Al4V microspheres were suspended into 5 M NaOH (60 °C/24 h) solutions, with extensive variations in microsphere:solution ratios to modify microsphere interaction and initiate self-assembly through proximity merging of titanate surface dendritic growth. The formed structures, which either produced 1) unbonded, sodium titanate-converted microspheres; 2) flat (non-macroporous) scaffolds; or 3) open, hierarchically porous scaffolds, were then assessed in terms of their formation mechanism, chemical composition, porosity, as well as the effect of post-heat treatments on compressive mechanical properties. It was found that specific microsphere:solution ratios tended to form certain structures (3 flat non-macroporous, >8 powder) due to a combination of microsphere freedom of movement, H2 gas bubble formation, and exposed surface reactivity. This promising discovery highlights the potential for lower temperature, simplistic production of 3D constructs with modifiable chemical properties due to the ion-exchange potential of titanate structures, with clear applications in a wide-range of fields, from medical materials to catalysts

Self-assembled titanium-based macrostructures with hierarchical (macro-, micro-, and nano) porosities: A fundamental study

This study details the novel self-assembly of sodium titanate converted Ti-based microspheres into hierarchical porous 3D constructs, with macro-, micro-, and nanoporosity, for the first time. Ti6Al4V microspheres were suspended into 5 M NaOH (60 °C/24 h) solutions, with extensive variations in microsphere:solution ratios to modify microsphere interaction and initiate self-assembly through proximity merging of titanate surface dendritic growth. The formed structures, which either produced 1) unbonded, sodium titanate-converted microspheres; 2) flat (non-macroporous) scaffolds; or 3) open, hierarchically porous scaffolds, were then assessed in terms of their formation mechanism, chemical composition, porosity, as well as the effect of post-heat treatments on compressive mechanical properties. It was found that specific microsphere:solution ratios tended to form certain structures (3 flat non-macroporous, >8 powder) due to a combination of microsphere freedom of movement, H2 gas bubble formation, and exposed surface reactivity. This promising discovery highlights the potential for lower temperature, simplistic production of 3D constructs with modifiable chemical properties due to the ion-exchange potential of titanate structures, with clear applications in a wide-range of fields, from medical materials to catalysts

Rapid synthesis of magnetic microspheres and the development of new macro–micro hierarchically porous magnetic framework composites †

Magnetic framework composites (MFCs) are a highly interesting group of materials that contain both metal–organic frameworks (MOFs) and magnetic materials. Combining the unique benefits of MOFs (tuneable natures, high surface areas) with the advantages of magnetism (ease of separation and detection, release of guests by induction heating), MFCs have become an attractive area of research with many promising applications. This work describes the rapid, scalable synthesis of highly porous magnetic microspheres via a flame-spheroidisation method, producing spheres with particle and pore diameters of 206 ± 38 μm and 12.4 ± 13.4 μm, respectively, with a very high intraparticle porosity of 95%. The MFCs produced contained three main iron/calcium oxide crystal phases and showed strong magnetisation (Ms: 25 emu g−1) and induction heating capabilities (≈80 °C rise over 30 s at 120 W). The microspheres were subsequently surface functionalised with molecular and polymeric coatings (0.7–1.2 wt% loading) to provide a platform for the growth of MOFs HKUST-1 and SIFSIX-3-Cu (10–11 wt% loading, 36–61 wt% surface coverage), producing macro–micro hierarchically porous MFCs (pores > 1 μm and <10 nm). To the best of our knowledge, these are the first example of MFCs using a single-material porous magnetic scaffold. The adaptability of our synthetic approach to novel MFCs is applicable to a variety of different MOFs, providing a route to a wide range of possible MOF–microsphere combinations with diverse properties and subsequent applications