Transient elastic support for vein grafts using a constricting microfibrillar polymer wrap

Abstract

Arterial vein grafts (AVGs) often fail due to intimal hyperplasia, thrombosis, or accelerated atherosclerosis. Various approaches have been proposed to address AVG failure, including delivery of temporary mechanical support, many of which could be facilitated by perivascular placement of a biodegradable polymer wrap. The purpose of this work was to demonstrate that a polymer wrap can be applied to vein segments without compromising viability/function, and to demonstrate one potential application, i.e., gradually imposing the mid-wall circumferential wall stress (CWS) in wrapped veins exposed to arterial levels of pressure. Poly(ester urethane)urea, collagen, and elastin were combined in solution, and then electrospun onto freshly-excised porcine internal jugular vein segments. Tissue viability was assessed via Live/Dead staining for necrosis, and vasomotor challenge with epinephrine and sodium nitroprusside for functionality. Wrapped vein segments were also perfused for 24h within an ex vivo vascular perfusion system under arterial conditions (pressure = 120/80 mmHg; flow = 100 mL/min), and CWS was calculated every hour. Our results showed that the electrospinning process had no deleterious effects on tissue viability, and that the mid-wall CWS vs. time profile could be dictated through the composition and degradation of the electrospun wrap. This may have important clinical applications by enabling the engineering of an improved AVG.

Figure 1

Schematic showing a cross-sectional view of the vein /wrap complex.

Figure 2

(A) shows a low magnification SEM image of the PIJV segment with the electrospun polymer deposited onto its adventitial surface. (B) is an SEM image (taken at 500x magnification) of the adventitial surface of the PIJV after the polymer wrap was applied. Note the high porosity of the polymer wrap. (C) is an SEM image (taken at 500x magnification) showing the attachment of the polymer wrap to the vein. (D) is an SEM image (taken at 500x magnification of the luminal surface of the vein and shows a continuous endothelium layer which appears to have remained intact.

Figure 3

Representative vasomotor challenge results obtained using epinephrine (EPI) and sodium nitroprusside (SNP) to stimulate both a spun and a sham control PIJV segment. Since SNP was not administered until a full relaxation of the tissue was observed following stimulation with EPI, SNP was administered at different times for the sham and spun PIJVs. Outer diameter measurements of each PIJV segment over the duration of the experiments were normalized to the baseline outer diameter which was measured prior to administration of the first dose of EPI.

Figure 4

Results from vasomotor challenge experiments (N=4). There appears to be no significant difference in the level of contraction or dilation between the sham control and spun PIJVs. The data are presented as mean ± standard error of the mean.

Figure 5

H&E (A,B) and Masson’s trichrome images (C,D) for both before perfusion and after wrapping procedure (A,C) and after 24 hours of ex vivo perfusion (B,D). Note the uniform thickness of the polymer wrap prior to perfusion, and the absence of the polymer wrap in the post-perfusion images. The single-headed arrow indicates the vessel lumen. The double-headed arrow in (A) and (C) indicates the thickness of the polymer wrap, which was not detectable in (B) or (D).

Figure 6

(A): Normalized outer diameter over time for both sham and spun PIJVs under ART conditions. Note that the normalized diameter of the spun veins is markedly reduced compared to sham controls. Pressurized outer diameter (OD_p) was normalized to unpressurized outer diameter (OD_up) for each vein. (B): β-stiffness values for both sham and spun PIJVs under ART conditions over 24 hours.

Figure 7

Normalized CWS vs. time results from 24 hour ex vivo perfusions of electrospun polymer wrapped PIJV segments for each combination of polymers as shown in Table 1. Normalization was to CWS_o, the mean CWS level measured in an unwrapped vein under venous conditions (~25 KPa), which is represented by the lower dashed horizontal line. The middle dashed horizontal line indicates the mean CWS in a coronary artery (~120 KPa) [32]. The upper dashed line represents the mean CWS measured in an unwrapped vein (sham control) under ART conditions (~1.75 MPa). In the legend, ET stands for electrospinning time.