Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Predicting localised corrosion and mechanical performance of a PEO surface modified rare earth magnesium alloy for implant use through in-silico modelling.

In this study, the influence of a plasma electrolytic oxidation (PEO) surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process. First, a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification, which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning, followed by uniaxial tensile testing. Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model. In-vitro, it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified. While corrosion rates were ∼50% lower in the WE43-PEO modified specimens, the local geometric features of corroding surfaces remained similar to the unmodified WE43 group, however evolving after almost the double amount of time. We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested, and not just in the early stages of corrosion. Using the results from the testing framework, the model parameters of the surface-based corrosion model were identified for both groups. This enabled, for the first time, in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens. This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.

Linking the effect of localised pitting corrosion with mechanical integrity of a rare earth magnesium alloy for implant use.

This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface-based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.

Automated ex-situ detection of pitting corrosion and its effect on the mechanical integrity of rare earth magnesium alloy - WE43.

This study develops a three-dimensional automated detection framework (PitScan) that systematically evaluates the severity and phenomenology of pitting corrosion. This framework uses a python-based algorithm to analyse microcomputer-tomography scans (µCT) of cylindrical specimens undergoing corrosion. The approach systematically identifies several surface-based corrosion features, enabling full spatial characterisation of pitting parameters, including pit density, pit size, pit depth as well as pitting factor according to ASTM G46-94. Furthermore, it is used to evaluate pitting formation in tensile specimens of a Rare Earth Magnesium alloy undergoing corrosion, and relationships between key pitting parameters and mechanical performance are established. Results demonstrated that several of the parameters described in ASTM G46-94, including pit number, pit density and pitting factor, showed little correlation to mechanical performance. However, this study did identify that other parameters showed strong correlations with the ultimate tensile strength and these tended to be directly linked to the reduction of the cross-sectional area of the specimen. Specifically, our results indicate, that parameters directly linked to the loss of the cross-sectional area (e.g. minimum material width), are parameters that are most suited to provide an indication of a specimen's mechanical performance. The automated detection framework developed in this study has the potential to provide a basis to standardise measurements of pitting corrosion across a range of metals and future prediction of mechanical strength over degradation time.

Influence of surface condition on the degradation behaviour and biocompatibility of additively manufactured WE43.

The further development of future Magnesium based biodegradable implants must consider not only the freedom of design, but also comprise implant volume reduction, as both aspects are crucial for the development of higher functionalised implants, such as plate systems or scaffold grafts in bone replacement therapy. As conventional manufacturing methods such as turning and milling are often accompanied by limitations concerning implant design and functionality, the process of laser powder bed fusion (LPBF) specifically for Magnesium alloys was recently introduced. In addition, the control of the degradation rate remains a key aspect regarding biodegradable implants. Recent studies focusing on the degradation behaviour of additively manufactured Magnesium scaffolds disclosed additional intricacies when compared to conventionally manufactured Magnesium parts, as a notably larger surface area was exposed to the immersion medium and scaffold struts degraded non-uniformly. Moreover, chemical etching as post processing technique is applied to remove sintered powder particles from the surface, altering surface chemistry. In this study, cylindrical Magnesium specimens were manufactured by LPBF and surfaces were consecutively modified by phosphoric etching and machining. Degradation behaviour and biocompatibility were then investigated, revealing that etched samples exhibited the overall lowest degradation rates, but experienced large pit formation, while the reduction of surface roughness resulted in a delay of degradation.

Microstructure, mechanical properties, corrosion resistance and cytocompatibility of WE43 Mg alloy scaffolds fabricated by laser powder bed fusion for biomedical applications.

Open-porous scaffolds of WE43 Mg alloy with a body-center cubic cell pattern were manufactured by laser powder bed fusion with different strut diameters. The geometry of the unit cells was adequately reproduced during additive manufacturing and the porosity within the struts was minimized. The microstructure of the scaffolds was modified by means of thermal solution and ageing heat treatments and was analysed in detail by means of X-ray microtomography, optical, scanning and transmission electron microscopy. Moreover, the corrosion rates and the mechanical properties of the scaffolds were measured as a function of the strut diameter and metallurgical condition. The microstructure of the as-printed scaffolds contained a mixture of Y-rich oxide particles and Rare Earth-rich intermetallic precipitates. The latter could be modified by heat treatments. The lowest corrosion rates of 2-3 mm/year were found in the as-printed and solution treated scaffolds and they could be reduced to ~0.1 mm/year by surface treatments using plasma electrolytic oxidation. The mechanical properties of the scaffolds improved with the strut diameter: the yield strength increased from 8 to 40 MPa and the elastic modulus improved from 0.2 to 0.8 GPa when the strut diameter increased from 275 µm to 800 µm. Nevertheless, the strength of the scaffolds without plasma electrolytic oxidation treatment decreased rapidly when immersed in simulated body fluid. In vitro bicompatibility tests showed surface treatments by plasma electrolytic oxidation were necessary to ensure cell proliferation in scaffolds with high surface-to-volume ratio.

Protective antibody response following oral vaccination with microencapsulated Bacillus Anthracis Sterne strain 34F2 spores.

An oral vaccine against anthrax (Bacillus anthracis) is urgently needed to prevent annual anthrax outbreaks that are causing catastrophic losses in free-ranging livestock and wildlife worldwide. The Sterne vaccine, the current injectable livestock vaccine, is a suspension of live attenuated B. anthracis Sterne strain 34F2 spores (Sterne spores) in saponin. It is not effective when administered orally and individual subcutaneous injections are not a practical method of vaccination for wildlife. In this study, we report the development of a microencapsulated oral vaccine against anthrax. Evaluating Sterne spore stability at varying pH's in vitro revealed that spore exposure to pH 2 results in spore death, confirming that protection from the gastric environment is of main concern when producing an oral vaccine. Therefore, Sterne spores were encapsulated in alginate and coated with a protein shell containing poly-L-lysine (PLL) and vitelline protein B (VpB), a non-immunogenic, proteolysis resistant protein isolated from Fasciola hepatica. Capsule exposure to pH 2 demonstrated enhanced acid gel character suggesting that alginate microcapsules provided the necessary protection for spores to survive the gastric environment. Post vaccination IgG levels in BALBc/J mouse serum samples indicated that encapsulated spores induced anti-anthrax specific responses in both the subcutaneous and the oral vaccination groups. Furthermore, the antibody responses from both vaccination routes were protective against anthrax lethal toxin in vitro, suggesting that further optimization of this vaccine formulation may result in a reliable oral vaccine that will conveniently and effectively prevent anthrax in wildlife populations.