Synthesis of polymers and copolymers of lactide through titanium initators

The research described in this thesis explored the synthesis tlnd characteristltion of biocompatible and biodegradable polymers of lactide through non-toxic titanium alkoxide nitiators. The research objectives focused on the preparation of polylactides in both solvent and solventless media, to produce materials with a wide range of molecular weights. The polylactides were fully characterised using gel permeation chromatography and 1H and 13C NMR spectroscopy. NMR spectroscopy was carried out in the study the reaction mechanisms. Kinetic studies of the ring opening polymerisation of lactide with titanium alkoxide initiators were also conducted using NMR spectroscopy. The objectives of this research were also focused on the enhancement of the flexibility of the polymer chains by synthesising random and block copolymers of lactide and ε-caprolactone using Ti(0-i-Pr)4 as an initiator, This work involved extensive characterisalion of the synthesised copolymers using gel permeation chromatography and 1H and 13C NMR spectroscopic analysis. Kinetic studies of the ring opening polymerisation of ε-caplrolactone and of the copolymerisation of lactide and ε-caprolactone with Ti(O-i-Pr)4 as an initiator were also carried out. The last section of this work involved the synthesis of block and star-shaped copolymers of lactide and poly(ethylene glycol) [PEG]. The preparation of lactide/PEG block copolymers was carried out by ring opening polymerisation of L-Iactide using Ti(O-i-Pr)4 as an initiator and hydroxyl-terminated PEG's with different numbers of hydroxyl groups as co-initiators both in solution and solventless media. These all-in-one polymersations yielded the synthesis of both lactide homopolymer and lactide/PEG block copolymer. In order to selectively synthesise copolymers of lactide and PEG, the experiment was carried out in two steps. The first step consisted of the synthesis of a titanium macro-initiator by exchanging the iso-propoxide ligands by PEG with different numbers of hydroxyl groups. The second step involved the ring opening polymerisation of lactide using the titanium macrocatalyst that was prepared as an initiator. The polymerisations were carried out in a solventless media. The synthesis of lactide/PEG copolymers using polyethylene glycol with amino terminal groups was also discussed. Extensive characterisation of the lactide block copolymers and macroinitiators was carried out using techniques such as, gel permeation chromatography (GPC), NMR spectroscopy and differential scanning calorimeter (DeS).

The relationship between fracture toughness and microstructure in titanium alloys

Linear Elastic Fracture Mechanics has been used to study the microstructural factors controlling the strength and toughness of two alpha-beta, titanium alloys. Fracture toughness was found to be independent of orientation for alloy Ti/6A1/4-V, but orientation dependent for IMI 700, bend and tension specimens giving similar toughness values. Increasing the solution temperature led to the usual inverse relationship between strength and toughness, with toughness becoming a minimum as the beta transus was approached. The production of a double heat treated microstructure led to a 100% increase in toughness in the high strength alloy and a 20% increase in alloy Ti/6A1/4V, with little decrease in strength. The double heat treated microstruoture was produced by cooling from the beta field into the alpha beta field, followed. by conventional solution treatment and ageing. Forging above the beta transus led to an increase in toughness over alpha beta forging in the high strength alloy, but had little effect on the toughness of Ti/6A1/4V. Light and electron microscopy showed that the increased toughness resulted from the alpha phase being changed from mainly continuous to a discontinuous platelet form in a transformed beta matrix. Void formation occurred at the alpha-beta interface and crack propagation was via the interface or across the platelet depending on which process required the least energy. Varying the solution treatment temperature produced a varying interplatelet spacing and platelet thickness. The finest interplatelet spacing was associated with the highest toughness, since a higher applied stress was required to give the necessary stress concentration to initiate void formation. The thickest alpha platelet size gave the highest toughness which could be interpreted in terms of Krafftt's "process zone size" and the critical crack tip displacement criterion by Hahn and Rosenfield from an analysis by Goodier and Field.

The effect of zinc and titanium on the structure of calcium-sodium phosphate based glass

An array of different structural probes has been used to define the effect of adding Zn and Ti to a sodium-calcium phosphate glass. X-ray absorption spectroscopy at the Zn K-edge suggests that the Zn atoms occupy mixed (4- and 6-fold) sites within the glass matrix. X-ray diffraction reveals a feature at 2.03 angstrom that develops with the addition of Zn and Ti and is consistent with Zn-O and Ti-O near-neighbour distances. Neutron diffraction is used to resolve two distinct P-O distances and highlights the decrease in P center dot center dot center dot P coordination number from 2.0 to 1.7 as the Ti metal concentration rises, which is attributed to the O/P fraction moving away from the metaphosphate value of 3.0 to 3.1 with the addition of Ti. Other correlations, such as those associated with CaO(x) and NaO(x) polyhedra, remain largely unaffected. These results suggest that the network forming P center dot center dot center dot P correlation is most disrupted, with the disorder parameter rising from 0.07 to 0.10 angstrom with the additional modifiers. Zn appears to be introduced into the network as a direct replacement for Ca and causes no structural variation over the composition range studied.

Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.

Titanium phosphate glass microspheres for bone tissue engineering

We have demonstrated the successful production of titanium phosphate glass microspheres in the size range of ~10-200 µm using an inexpensive, efficient, easily scalable process and assessed their use in bone tissue engineering applications. Glasses of the following compositions were prepared by melt-quench techniques: 0.5P2O5-0.4CaO-(0.1 - x)Na2O-xTiO2, where x = 0.03, 0.05 and 0.07 mol fraction (denoted as Ti3, Ti5 and Ti7 respectively). Several characterization studies such as differential thermal analysis, degradation (performed using a novel time lapse imaging technique) and pH and ion release measurements revealed significant densification of the glass structure with increased incorporation of TiO2 in the glass from 3 to 5 mol.%, although further TiO2 incorporation up to 7 mol.% did not affect the glass structure to the same extent. Cell culture studies performed using MG63 cells over a 7-day period clearly showed the ability of the microspheres to provide a stable surface for cell attachment, growth and proliferation. Taken together, the results confirm that 5 mol.% TiO2 glass microspheres, on account of their relative ease of preparation and favourable biocompatibility, are worthy candidates for use as substrate materials in bone tissue engineering applications.

Structural characterization of titanium-doped Bioglass using isotopic substitution neutron diffraction

Melt quenched silicate glasses containing calcium, phosphorus and alkali metals have the ability to promote bone regeneration and to fuse to living bone. Of these glasses 45S5 Bioglass® is the most widely used being sold in over 35 countries as a bone graft product for medical and dental applications; particulate 45S5 is also incorporated into toothpastes to help remineralize the surface of teeth. Recently it has been suggested that adding titanium dioxide can increase the bioactivity of these materials. This work investigates the structural consequences of incorporating 4 mol% TiO2 into Bioglass® using isotopic substitution (of the Ti) applied to neutron diffraction and X-ray Absorption Near Edge Structure (XANES). We present the first isotopic substitution data applied to melt quench derived Bioglass or its derivatives. Results show that titanium is on average surrounded by 5.2(1) nearest neighbor oxygen atoms. This implies an upper limit of 40% four-fold coordinated titanium and shows that the network connectivity is reduced from 2.11 to 1.97 for small quantities of titanium. Titanium XANES micro-fluorescence confirms the titanium environment is homogenous on the micron length scale within these glasses. Solid state magic angle spinning (MAS) NMR confirms the network connectivity model proposed. Furthermore, the results show the intermediate range order containing Na-O, Ca-O, O-P-O and O-Si-O correlations are unaffected by the addition of small quantities of TiO2 into these systems.

Growth of short fatigue cracks in titanium alloys

The initiation and early propagation of short fatigue cracks has been studied in detail in two alpha / beta titanium alloys as a function of microstructure. Detailed metallography is presented relating short crack growth rates to the microstructural features present. The work shows the significant differences in short crack propagation rates which can be achieved by microstructural changes within a single alloy.

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM. © 2014 Springer Science+Business Media.