Biodegradation Behavior And Biological Responses Of Magnesium-based Materials For Vascular Stents In The Hydrodynamic Near-Physiological Ambient Conditions

There is currently a paradigm shift in the medical implant device industry where absorbable metallic materials made from Magnesium (Mg) and Mg alloys are being reviewed to replace permanent metal implants. Even with the heavy volume of research that has been conducted, absorbable metals cannot be investigated using the current American Society for Testing and Materials (ASTM) and International Organization for Standards (ISO) standards, since the traditional in vitro test methods cannot predict the in vivo results. A key step of the development of current standards is to identify and test the relevant microenvironments and parameters in test-systems. Furthermore, with respect to clinical applications of absorbable Mg-based vascular stents, there needs to be a full understanding of the mechanisms of biodegradation of Mg-based stents, along with developing reliable methods for controlling degradation and biocompatibility.The main objective of this research is to better understand the effect of fluid dynamics on the Mg degradation, mimicking the vascular environment. We developed a series of vascular bioreactors to simulate in vivo/clinical conditions to reveal degradation mechanisms, such as in vitro varied fluid flow system with computational fluid dynamic calculation, in-situ or real-time electrochemical monitoring system, a porcine aortal bioreactor as well as a rat aortal in vivo system.The accurate determinations of the corrosion types, corrosion rate and corrosion products play a vital part in predicting the fate of magnesium-based stent. Experiments revealed that fluid hydrodynamics, fluid flow velocity, and shear stress play essential roles in the degradation/corrosion behavior of absorbable magnesium-based stent devices. Flow-induced shear stress (FISS) accelerates mass and electron transfer processes, leading to an increase in the entire corrosion, including localized, uniform, pitting and erosion corrosions. FISS increased the average uniform corrosion rate, the localized corrosion coverage ratios and depth, and the removal rate of corrosion products inside of corrosion pits. These results prodived a consistent correlation to the resistance of the uniform corrosion product layer, the resistance of localized corrosion and polarization resistance, which were investigated in the in-situ and real-time electrochemical test. In terms of the stents, the volume loss ratio at a FISS of 0.056 Pa was nearly twice that at a FISS of 0 Pa before and after corrosion. Flow direction has a significant impact on corrosion behavior as the corrosion product layer facing the flow direction peeled off from the stent struts.To understand progressive degradation behaviors of Mg associated to the different vascular remodelling stages, i.e. pre-and post-endothelialization stages, a porcine aortal bioreactor model and a rat aortal in vivo are developed to study flow convection and diffusion induced biodegradation behavior of Mg. The results revealed flow plays a dominant role on the corrosion rate in aortal bioreactor, and biological factors are more important on the corrosion rate in aortal in vivo model. The in vivo degradation was slower than the in vitro degradation. The established porcine aorta porcine aortal bioreactor and a rat aortal in vivo model is expected to provide more information for a better understanding of the degradation behavior of absorbable metallic stents.Concerning the corrosion-control and biocompatiblity of Mg-base stent, a surface-eroding coating of poly(1,3-trimethylene carbonate) (PTMC) on Mg alloy was studied, and its dynamic degradation behavior, electrochemical corrosion, hemocompatiblity and histocompatibility were investigated. The PTMC coating effectively protected the corrosion of the Mg alloy in the dynamic degradation test. The corrosion current density of the PTMC-coated alloy was reduced by three orders and one order of magnitude compared to controls, bare and poly(ε-caprolactone) (PCL)-coated Mg alloy, respectively. Static and dynamic blood tests in vitro indicated that significantly fewer platelets were adherent and activated, and fewer erythrocytes attached on the PTMC-coated surface and showed less hemolysis than on the controls. The PTMC coating after 16 weeks subcutaneous implantation in rats maintained-55%of its original thickness and presented a homogeneously flat surface demonstrating surface erosion; in contrast to the PCL coated control which exhibited non-uniform bulk erosion. The Mg alloy coated with PTMC showed less volume reduction and fewer corrosion products as compared to the controls after 52 weeks in vivo. Excessive inflammation, necrosis or hydrogen gas accumulation were not observed. The homogeneous surface erosion of the PTMC coating from exterior to interior (surface-eroding behavior) and its charge neutral degradation products contribute to its excellent protective performance. It is concluded that PTMC is a promising candidate for a surface-eroding coating applied to Mg-based stents.This study demonstrates that flow-induced corrosion should be understood to properly design Mg-based stents in vascular environments. The experimental data in this dissertation are expected to reduce the gap between in vivo and in vitro test results, as well as, provide more accurate information to better understand degradation behavior of absorbable metallic stents.