Tissue reactions to polyethylene glycol and glutaraldehyde-based surgical sealants in a rabbit aorta model

Abstract

Surgical sealants help achieve rapid haemostasis when applied as an adjunct to sutures in vascular surgery, but their use can lead to various side effects. This study compared the local inflammatory reaction to commercially available BioGlue and Coseal sealants in a rabbit aorta suture hole model. Twenty male New Zealand white rabbits were randomised to testing with either BioGlue or Coseal. Two weeks after sealant application to suture holes, sections of the aorta at the puncture site, and surrounding tissue, were processed for histopathological analysis. Inflammation was graded from 0 to 3 according to tissue alteration and presence of inflammatory cells. Material stiffness was measured in vitro using compression testing. From examination of the inflammatory response to the sealants, a less severe histopathological assessment score was assigned to the Coseal compared to the BioGlue group (mean ± SD: 1.56 ± 0.53 vs 2.67 ± 0.50; p = 0.002). While both materials triggered a typical foreign body reaction characterised by granulomatous inflammation, BioGlue additionally provoked eosinophilic cell infiltration. Lymphocytes, plasma cells and B cells were also more prevalent in the BioGlue compared to the Coseal specimens. Coseal residue was either absent or visible in only small quantities, while significant BioGlue deposits remained in the tissue 2 weeks after application. Coseal was much more elastic than BioGlue, with a compressive modulus an order of magnitude lower (mean ± SD: 91 ± 41 vs 1833 ± 297 kPa). Compared to BioGlue, Coseal elicited a less pronounced inflammatory response in the aortic and peri-aortic tissue in this model, and demonstrated greater elasticity.

Keywords: Anastomosis; BioGlue; Coseal; inflammation; stiffness; surgical sealant.

Figure 1.

Representative images of the application sites after 2 weeks: (a) BioGlue, *aorta, grey box: area of application and tissue reaction; (b) Coseal, *aorta, grey box: area of application and tissue reaction%; (c) opened tissue capsule that surrounded the BioGlue residue.

Figure 2.

(a) BioGlue; (b) Coseal: in both groups inflammatory cells (*) were localised predominantly around the aorta, demonstrating segmental circular fragmentation (arrowheads) of the vessel wall, scale bar = 400 μm.

Figure 3.

(a) Mean (±standard deviation (SD)) of grades given by investigators at centre 1; (b) Mean (±SD) of grades given by investigators at centre 2. p-Values were calculated using a Mann–Whitney U test. Inflammation grade: none (0); mild (1); moderate (2); severe (3). The use of means in the figure is for the purpose of illustration.

Figure 4.

(a and b) BioGlue, Pattern A: (a) Intense granulomatous inflammation, scale bar = 150 μm, material residues are marked with *; (b) Note lymphocytes, plasma cells, multinucleated giant cells (arrows) and many intensively eosinophilic-stained granulocytes (arrowheads), scale bar = 40 μm; (c and d), Coseal, Pattern B: (c) Moderate granulomatous inflammation (arrowheads), scale bar = 150 μm; (d) note the presence of many macrophages (arrowheads) and few lymphocytes, scale bar = 40 μm. Localisation of high magnification images are highlighted in the low-power images.

Figure 5.

(a to c) BioGlue, Pattern A: (a) HE staining demonstrating a mixed pattern of epithelioid cells (arrowheads), eosinophilic granulocytes (arrows) and a few plasma cells and lymphocytes, scale bar = 30 μm; (b) Luna staining showing numerous intensively stained (red) eosinophilic granulocytes (arrowheads), scale bar = 30 μm; note that erythrocytes reveal a similar staining pattern, but can be differentiated in high power images as they do not contain nuclei; (c) CD79a immunostaining indicate that many cells of the infiltrate comprise B-lymphocytes (arrowheads), scale bar = 40 μm; (d to f) Coseal, Pattern B: (d) HE staining demonstrating granulomatous inflammation comprising epitheloid cells (arrows), scale bar = 30 μm; (e) Just single eosinophilic granulocytes can be found by Luna staining (arrowheads), scale bar = 30 μm; (f) Some immunopositive B-cells can be demonstrated by CD79a immunohistochemistry (arrowheads), scale bar = 40 μm.

Figure 6.

(a) Stress–strain curve resulting from compression of sealant samples; (b) Comparison of compressive moduli for sealant samples showing mean (central line), SD (bars) and individual sample values (squares/dots).