Evaluation of FeMnN alloy bioresorbable flow diverting stents in the rabbit abdominal aorta

Abstract

Flow diverting stents are braided, metallic endoluminal devices widely used to treat intracranial aneurysms. Bioresorbable flow diverters (BRFDs) are gaining traction as the next generation of flow diverter technology. BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body, mitigating or eliminating complications associated with the permanent presence of conventional flow diverters such as thromboembolism and stenosis. Additional putative advantages of a BRFD include a reduction in metal induced medical imaging artifacts, a restoration of physiological vasoreactivity, and allowing physicians to re-access the aneurysm if an additional procedure is required. In this current study, iron-manganese-nitrogen (FeMnN) alloy BRFDs and permanent control FDs composed of an industry standard Cobalt-Nickel-Chromium alloy were deployed in the rabbit aorta. MicroCT and SEM corrosion analysis determined the FeMnN wire volumes and cross-sectional areas had reduced approximately 85 % and 95 % after 3- and 6-months implantation duration, respectively. Histological analysis demonstrated the BRFDs exhibited suitable biocompatibility, with no cases of in-stent thrombosis, clinically significant stenosis, or adverse tissue responses observed. Immunohistochemistry revealed the neointimas surrounding the BRFDs featured a confluent endothelium covering several layers of smooth muscle cells, with macrophages adjacent to the device wires. The macrophages were able to penetrate the corrosion product and were observed transporting corrosion products away from the implant site. This current work provides primary in vivo corrosion and biocompatibility data to the field for FeMn alloys, which we feel will stimulate and inform the design of next-generation bioresorbable endovascular devices.

Keywords: Biodegradable; Bioresorbable; Flow diverter; Rabbit aorta; Stent.

Graphical abstract

Fig. 1

Representative (A) radiograph and (B) Digital subtraction angiogram of a BRFD and Control FD immediately after deployment in the rabbit infrarenal abdominal aorta. (C) Digital subtraction angiogram of the BRFD and Control FD at the 6-month follow up. (D) Quantified % Stenosis of the Control FDs and BRFDs after 3 or 6 months in the aorta. There was no statistical significance between any groups.

Fig. 2

(A) Representative microCT 3D renderings of a BRFD deployed in the rabbit aorta for 0 (baseline), 3, or 6 months. Red represents tantalum wires and white represents FeMnN wires. (B) Quantified normalized volume of FeMnN in the BRFDs after 0 (baseline), 3, or 6 months of deployment in the rabbit aorta.

Fig. 3

(C) Representative SEM micrograph of a BRFD deployed in the rabbit aorta for 3 months demonstrating the variability in corrosion of FeMnN wires. “Fe1”, “Fe2”, and “Fe3” indicate FeMnN wires that have barely, partially, or completely corroded, respectively. “T” indicates a permanent tantalum wire. (B, C) FeMnN wire cross sectional area reductions normalized to non-implanted baseline FeMnN wires, as assessed by SEM. In both plots, every point represents an individual wire cross section. (B) All measured wires from different rabbits were grouped for the 3- and 6-month endpoints. The solid and dashed lines represent the group mean and median, respectively. (C) The measured wires were separated, with each boxplot representing measurements from a different rabbit.

Fig. 4

Representative backscatter (BSE) and associated SEM-EDS elemental maps of partially and fully degraded FeMnN wires after 3 or 6 months of deployment within the rabbit aorta. The scale bars are 25 μm.

Fig. 5

(A) Representative low magnification images of H&E-stained cross sections of rabbit aortas implanted with a control FD or BRFD for 3 or 6 months. (B) Representative high magnification images of H&E-stained cross sections of rabbit aortas implanted with a BRFD for 3 or 6 months. The L indicates the lumen of the aorta. The solid arrows indicate what appear to be foreign body giant cells forming at the implant interface. The dashed arrows indicate iron-laden cells that appear to be transporting corrosion products away from the implant interface.

Fig. 6

Neointimal morphometrics measured from H&E-stained cross sections of Control FDs and BRFDs deployed in the infrarenal rabbit abdominal aorta for 3 or 6 months. For all three metrics, there was no statistical significance between the 3- and 6-month groups for each device type.

Fig. 7

Representative high magnification images of aortas implanted with control FDs or BRFDs for 3 or 6 months stained with α-SMA (smooth muscle cells – top row), RAM11 (macrophages – middle row), or CD31 (endothelial cells – bottom row) antibodies. In all the images, the antibody staining appears red, all cell nuclei were counterstained blue, and the L indicates the lumen of the aorta.

Fig. 8

Concentration of Fe and Mn in the rabbit serum before BRFD deployment (Pre) and immediately prior to sacrifice (Post). Blue data points represent rabbits with a 3-month implant duration, black data points represent rabbits with a 6-month implant duration.