Metallic zinc exhibits optimal biocompatibility for bioabsorbable endovascular stents

Abstract

Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells.

Keywords: Bioabsorbable; Biocompatible; Corrosion; Hyperplasia; Stent; Zinc.

Figure 1

H&E stained sections from excised high purity zinc wires (250 µm nominal diameter) after residence in the arterial lumen for 2.5, 4, and 6.5 months (n = 2 per time point), showing benign neointimal formation and a healthy artery. Black arrow at 10× magnification identifies the position of the zinc wire, which is surrounded by a neointima (wire cross sections were dislodged during sectioning). Black arrow at 60× magnification identifies the neointima on the luminal side, which never exceeds 100 µm in thickness in any of the six specimens examined. Red stars in the images identify the position of the zinc wires. Yellow stars in the images identify regions of low cell density near the zinc wire, which contrast strikingly with the high-cell density regions further away from the zinc wire. Dark green arrows identify cell and tissue regeneration inside the zinc implant. Light green arrowheads identify cells within the corrosion layer, highlighting the excellent biocompatibility of zinc corrosion products. Tissue regeneration can be seen at 6.5 months. Scale bars: 10× = 500 µm, 20× = 200 µm, 60× = 100 µm, and 100× = 50 µm.

Figure 2

Neointimal tissue thickness at the luminal vs. mural side of the implant (A) and cell density near the implant vs. near the blood interface (B). Significance values were determined via the Student’s t-test.

Figure 3

H&E stained cross sections of wire implants showing typical regions of wire that were not in contact with the arterial wall. Upper images show 4- (A) and 6.5-month (B) implants at 40× magnification. Lower images (C & D) show high magnification images (100×) of the 6.5-month cross section shown in panel B. Note that the wire cross-section was dislodged during cryo-sectioning.

Figure 4

Cross sections were stained for endothelial cells (red, CD31, left panels), smooth muscle cells (red, α-actin, right panels), and cell nuclei (DAPI counterstained blue, both panels) at 2.5 and 6.5 months. The green arrow in each panel identifies a characteristic region of positive staining within the neointimal tissue. Note that the corrosion layer impregnating the center of the neointimal tissue is excited and fluoresces red in these images.