Deciphering the relationship between bioresorbable magnesium alloy corrosion and the inflammatory microenvironment of the neotinima - Summary A new generation of bioresorbable metal stents using magnesium (Mg) is currently being developed and tested clinically. The research team is motivated by recent clinical data to explore whether local changes in the atherosclerotic inflammatory microenvironment can exert a considerable shift in the biocorrosion of Mg alloys. Additionally, the team is interested in understanding how corrosion products from the metals influence neointimal progression. Therefore, the objectives of this project are to: I) clarify how physiologically relevant atherosclerotic inflammatory microenvironments affect the corrosion progression of Mg based materials, and II) determine whether Mg corrosion can exert measurable changes in the progression of the neointima, using advanced elemental imaging and large-scale data collection in an APOE-/- KO mouse model. First, an in vitro co-culture model will be run, using key atherosclerotic inflammatory cells (foam cells) that are implicated in plaque progression and will characterize their cellular behavior when exposed to clinically used Mg alloys (WE43) and other clinically relevant Mg alloys (AZ31, WE22, ZA41). The team will then determine if their modulation of the microfluidic degradation environment via secreted reactive species can exert considerable shifts in the corrosion progression of Mg alloys in Aim I. For Aims II and III, the team will implant the Mg alloys in atherogenic APOE-/- transgenic mice. Aim II will focus on using an elemental imaging system, which will allow for in situ element detection at high resolution and sensitivity. The team will describe the relationship between the in-situ presence of implant derived trace metals and inflammation. Aim III will explore the global relationships between Mg alloys, neointimal characteristics, and biological variables. Here, the corrosion rate of Mg alloys in diseased animals will be described and compared to healthy animal controls. Overall, these aims will allow the team to determine whether 1) diseased neointimal microenvironments influence the corrosion rate of Mg alloys, and 2) if neointimal progression is related to the biocorrosion of Mg alloys. This will be accomplished by using large scale histological data collection, and dimensional reduction techniques. This work will aid in deciphering the failure mechanisms of Mg stents in the clinic and help bioengineers and clinicians identify more corrosion resistant and biocompatible Mg alloys.
