Multidimensional analysis for the correlation of physico-chemical attributes to osteoblastogenesis in TiNbZrSnTa alloys.

Data-enabled approaches that complement experimental testing offer new capabilities to investigate the interplay between chemical, physical and mechanical attributes of alloys and elucidate their effect on biological behaviours. Reported here, instead of physical causation, statistical correlations were used to study the factors responsible for the adhesion, proliferation and maturation of pre-osteoblasts MC3T3-E1 cultured on Titanium alloys. Eight alloys with varying wt% of Niobium, Zirconium, Tin and Tantalum (Ti- (2-22 wt%)Nb- (5-20 wt%)Zr- (0-18 wt%)Sn- (0-14 wt%)Ta) were designed to achieve exemplars of allotropes (incl., metastable-ß, ß + α', α″). Following confirmation of their compositions (ICP, EDX) and their crystal structure (XRD, SEM), their compressive bulk properties were measured and their surface features characterised (XPS, SFE). Because these alloys are intended for the manufacture of implantable orthopaedic devices, the correlation focuses on the effect of surface properties on cellular behaviour. Physico-chemical attributes were paired to biological performance, and these highlight the positive interdependencies between oxide composition and proliferation (esp. Ti4+), and maturation (esp. Zr4+). The correlation reveals the negative effect of oxide thickness, esp. TiOx and TaOx on osteoblastogenesis. This study also shows that the characterisation of the chemical state and elemental electronic structure of the alloys' surface is more predictive than physical properties, namely SFE and roughness.

In-silico design and experimental validation of TiNbTaZrMoSn to assess accuracy of mechanical and biocompatibility predictive models.

Numerical design of TiNbTaZrMoSn alloy preceded its manufacture and mechanical, physico-chemical and in vitro characterisation. The specifications of the alloy required a multi-objective optimisation including lower modulus of elasticity than c.p.Ti, high strength, stabilised ß crystal structure with a low martensitic start temperature, a narrow solidification range and high biocompatibility. The results reveal that there was a good match between the bulk mechanical properties exhibited by the alloy experimentally and those predicted. Regarding surface properties, independent of roughness effects, the oxide thickness and surface zeta-potential, measured in biologically relevant electrolytes and at physiological pH, arose as important factors in osteoblastic activity (i.e., cell proliferation, measured via DNA, protein and metabolite content, and differentiation, via ALP levels), but not in cell adhesion and viability. The thinner oxide layer and lower absolute value of surface zeta-potential on the TiNbTaZrMoSn alloy explain its lesser osteogenic properties (i.e., inhibition of ALP activity) compared to the c.p. Ti. This study demonstrates that the numerical models to predict microstructure and bulk mechanical properties of ß-Ti alloys are robust, but that the prediction of cellular bioactivity lags behind and still requires parameterisation to account for features such as oxide layer composition and thickness, electro-chemical properties and surface charge, and topography to optimise cell response in silico before committing to the costly manufacture and deployment of these alloys in regenerative medicine.

Synthetic bone: Design by additive manufacturing.

A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to propose new conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii) the mechanical properties - stiffness and strength - are experimentally measured, evaluated, and compared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants. STATEMENT OF SIGNIFICANCE: We present a conceptual bio-engineering design methodology for new biomedical lattices produced by additive manufacturing, which addresses some of the critical points in currently existing porous implant materials. Amongst others: (i) feasibility and accuracy of manufacturing, (ii) design to the elastic properties of bone, and (iii) sensible pores sizes for osseointegration. This has inspired new and novel geometrical latticed designs which aim at improving the properties of intervertebral fusion devices. In their fundamental form, these structures are here fabricated and tested. When integrated into medical devices, these concepts could offer superior medical outcomes.