The field of biodegradable metals is fast evolving and expanding to new potential biometal candidates such as various alloying systems, coatings, fabrication processes or usage of new encouraging base materials (e.g. molybdenum). In those research fields the question of biocompatibility is often tried to address with simple and fast cytotoxicity assays, without realizing that the corrosion behavior and the specific environment have a substantial influence on the corrosion of the metal. After receiving the cytotoxicity results there are still many questions how these results represent the performance of the candidate metals in vivo in preclinical in animal models or even in humans. This lecture is aiming to provide an overview on the corrosion performance of different biodegradable metals (magnesium, zinc and iron) in different environments from atmospheric conditions over in vitro and in vivo to in humans. In vitro, choice of corrosion media, pH and/or mechanical stimulation influence corrosion performance and calculation of corrosion rate can additionally vary in dependence of the used test method (e.g. electrochemical measurement or weight/ volume loss). In vivo, the surrounding tissue with a huge variance in blood supply, inflammatory processes and the availability of corrosion accelerating elements has an impact on corrosion rate and morphology, which cannot be fully addressed in in vitro settings. Additionally, availability and applicability of test systems differ to in vitro settings, with mainly µ-computed tomography as tool to calculate corrosion rates. However, in dependence to the used CT-system a differentiation between original material and corrosion layer is not always possible, which limits comparable calculation of in vivo corrosion rates. Calculation of corrosion in humans is even more challenging, as radiographic follow ups often are restricted due to ethical issues and the assessment is limited in magnetic tomographic imaging, Finally, the use of in silico methods for corrosion prediction will be addressed. Overall, the here presented comparison of in vitro, in vivo, in human and in silico methods can help in the choice of methods as well as in the interpretation of obtained results when corrosion performance of new promising biodegradable metals is evaluated, which directly influences in vivo or in human performance with regard to biocompatibility and functionality.

The development and testing of new biodegradable metal implants is a time- and resource-consuming process that can generally be divided into in vitro testing and preclinical and clinical in vivo testing. For a long time one main objective to accelerate this process has been to enable a correlation between in vitro and in vivo corrosion rates. In silico methods can facilitate this process and, moreover, they can also be applied to predict the bone growth surrounding the implant. While models of varying detail and complexity exist, we are presenting an approach in which ordinary differential equations (ODEs) are used to model the degradation rate of magnesium-based implants, both in vitro and ex vivo, as well as the bone growth and its mineralization. For comparison, the bone growth surrounding titanium implants is also modelled. With these models, we aim to find a correlation between degradation rates in varying testing scenarios, as well as the degradation and bone growth, such that we may predict in vivo degradation and bone growth based solely on in vitro degradation rates.

The growing scientific interest in zinc stems from its optimal degradation rate, which makes it suitable to produce implants intended for temporary presence in the human body. However, zinc suffers from low mechanical properties and its recrystallization temperature is close to room temperature. This is why the immediate application of zinc in medicine is unattainable. Therefore, research focused on enhancing the mechanical properties of zinc-based materials and controlling their microstructural changes during stent manufacturing is of great importance. The studies have demonstrated that zinc-magnesium is a viable candidate material for producing absorbable stents. Despite its low recrystallization temperature, careful selection of manufacturing methods can yield high-strength implants with appropriate degradation rates and cell responses.

While the foreign body reaction for traditional implant materials has been thoroughly described, there is a general lack of information regarding the dynamic inflammatory response towards bioabsorbable metals. Complicating the matter further, studies have demonstrated that the microstructure of absorbable metals plays a key role in regulating immune reactions, however emphasis has been mostly placed on the long-term response, without much consideration to the acute phase reaction. The goal of this study is to investigate the impact of microstructurally distinct and clinically relevant magnesium-aluminum (Mg-Al) implants and its impact on acute inflammation in vivo. We describe the corrosion behavior of Mg-Al implants in vitro and in vivo, and describe relationships between inflammation and corrosion behavior. This work indicates a persistent acute phase inflammatory reaction, possibly exacerbated by residual Mg17Al12 particles which are more noble and likely undegraded. This work will directly aid in future efforts to identify appropriate Mg microstructures not only for manipulating corrosion and mechanical performance, but also for tuning the inflammatory response towards more regenerative reactions.

Biodegradable cardiovascular stents have the potential to treat vascular occlusion as a temporary device, allowing for the possibility of reintervention. Additionally, these devices reduce the need for long-term antithrombotic therapies, which are known to increase patients’ bleeding risk. Understanding the acute thrombosis response of any vascular devices, is critical. Mg alloys have so far led in the development of biodegradable stents, but preclinical and clinical testing is nearly always completed with antiplatelet therapies. This work tested the in vitro and ex vivo responses of a variety of developed Mg alloys in a highly prothrombotic model to characterize the alloys’ responses and identify the mechanism causing these changes occur. Mg alloy wires were obtained from Ft Wayne Metals and CoCr wires were used as a clinical control. In vitro testing was performed to quantify factor (F)XIIa and fibrin generation, indicating early and late ends of the contact pathway of coagulation, respectively. Ex vivo testing was completed using a non-human primate model of acute thrombogenesis without antiplatelet therapies. Autologous platelets and homologous fibrin were radiolabelled with 111-In and 125-I, respectively, to quantify the thrombus generation over 1hr exposure to flowing, whole blood. Downstream blood samples allowed for testing of the wire microenvironment. Thrombi on the wires were qualitatively characterized with SEM. The Mg alloys consistently showed lower thrombogenicity compared to the CoCr control. Specifically, they had slower fibrin take off times, decreased quantities of FXIIa generation, and lower platelet and fibrin attachment ex vivo. Ex vivo results demonstrated the significantly lower quantities of platelets and fibrin on the wire coils after 1hr of flowing, whole blood for ZX10 and WE43, compared to CoCr. The Mg alloy results reflect previous observations of low thrombogenicity for pure Mg, suggesting that alloying did not limit the anti-thrombotic effects of Mg. However, given the observed gas development on the wires, it is unclear whether this reduction in thrombosis is inherent to Mg ions or if it is a biophysical prevention of protein adsorption and therefore thrombosis. Ongoing work is examining a Mg alloy after surface treatment to determine the effects of surface passivation on thrombogenicity.