Assessing the suitability of titanium scaffold architectures and alloy compositions for bone tissue engineering

Titanium has long been considered the ‘gold standard’ for orthopaedic implants, yet discrepancies in the elastic modulus between host bone and implant has increased the prevalence of the <b>stress-shielding</b> effect, and the recession of implant-adjacent bone. An effect that also propagates <b>aseptic loosening</b>, and the loss of implant fixation due to inadequate osseointegration, towards eventual implant failure. This has caused an unrequited increase in joint replacement revisions and placed an immense global financial burden on health care providers.This thesis has identified two approachesthat harnessed: the physical architecture of porous Titanium scaffolds manufactured using selective laser melting; and the chemical composition and crystallographic structure of Titanium alloys, to improve mechanical suitability and drive osseointegration, and therefore negate both <b>stress-shielding</b> and <b>aseptic loosening</b>, with a clear aim to increase implant longevity.In this thesis, it was reported that both approaches improved mechanical suitability, shown by a reduced elastic modulus, whilst retaining a suitably high compressive strength – thereby adhering to the <b>stress-shielding</b> effect. Under compressive load, a suitable spread of compressive forces was observed in porous scaffolds, with a reported, appropriate elastic modulus that would indicate beneficial delay/negation of the <b>stress-shielding</b> effect, bar an open strut-based structure which crumpled on scaffold collapse. In parallel, compression testing revealed all alloys reported a reduced elastic modulus compared to commercially pure Titanium, but still above values expected of load-bearing bone, and thus would not negate, but may delay the <b>stress-shielding</b> effect.Furthermore, an in-vitro murine pre-osteoblast cell line, MC3T3-E1, model was used to show that specific geometrical cues and an optimised elemental composition can assist cell retention, colony growth &amp; maturation – creating a stronger union within the bone/implant interface, preventing <b>aseptic loosening</b>. The results presented showed that open strut-based structures suffered from cell attrition and delayed colony growth, whilst a larger maturation extent was promoted when the intrinsic micro-porosity, unique to selective laser melting, matched greater that of osteoblast protrusion, inducing cell elongation and duress, known to be favourable for osteogenesis^[1,2], reducing the risk of <b>aseptic loosening</b>. In parallel, the composition of these quaternary and quinary alloys greatly influenced the cell response, mediated through the surface chemistry. The results presented clearly demonstrate the suitability of these β and α” + β alloys, of a varied composition of Niobium, Tin, Tantalum and Zirconium, to enhance osseointegration and halt the progression of <b>aseptic loosening</b>.The outcome of this research intends to provide a systematic report of the influence of both the physical and chemical approaches in which Titanium can be finetuned to maximise suitability for orthopaedic load-bearing implantation purposes. It is proposed that these approaches will increase the longevity, minimise the rate and requirement for joint replacement revisions, and therefore the overall, intrinsic and financial, success of Titanium-based implants.