The effect of biological sealants and adhesive treatments on matrix metalloproteinase expression during renal injury healing

Abstract

Background: Renal injuries are relatively common in cases of abdominal trauma. Adhesives and sealants can be used to repair and preserve damaged organs. Using a rat model, this study explores the activity of different matrix metalloproteinases (MMP) during the healing of renal injuries treated by two biological adhesives (TachoSil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex).

Methods: Renal traumatic injuries were experimentally induced in 90 male Wistar rats by a Stiefel Biopsy Punch in the anterior aspect of the left kidney. Animals were divided into five groups: 1, sham non-injured (n = 3); 2, non-treated standard punch injury (n = 6); 3, punch injury treated with TachoSil (n = 27); 4, punch injury treated with GelitaSpon (n = 27); and, 5, punch injury treated with Adhflex (n = 27). Wound healing was evaluated 2, 6, and 18 days after injury by determining the expression of MMPs, and the histopathological evolution of lesions.

Findings: Histologically, the wound size at 6 days post-injury was larger in Adhflex-treated samples than in the other treatments, but the scarring tissue was similar at 18 days post-injury. Only the MMPs subtypes 1, 2, 8, 9, and 13 were sufficiently expressed to be quantifiable. Both time since injury and treatment type had a significant influence on MMPs expression. Two days after injury, the expression of MMP8 and MMP9 was predominant. MMP2 expression was greater 6 days after injury. The Adhflex-treated group had a significantly higher MMPs expression than the other treatment groups at all healing stages.

Conclusions: All three sealant treatments induced almost similar expression of MMPs than untreated animals indicating a physiological healing process. Given that all renal trauma injuries must be considered emergencies, both biological and synthetic adhesives, such as Adhflex, should be considered as a treatment options.

Fig 1. Metalloproteinases expression in sham-control, non-treated and treated (Adhflex, GelitaSpon and TachoSil) kidneys.

(A) Chart showing the most expressive metalloproteinase; (B) ELISA MMP panel (R&D Systems) plates of the rat metalloproteinase in all groups; (C) Individual graphs for the most expressed metalloproteinases in all groups (control, non-treated, and Adhflex, GelitaSpon and TachoSil treated) tested at 2, 6 and 18 days post-injury. Mann-Whitney U test: (*), p<0.05 as compared to untreated animals; (‡), p<0.05 as compared to Adhf® group; (†), p<0.05 as compared to GelSp® group. Kruskal-Wallis test shows the statistical differences among four groups in each healing time period. (^ns): no significance.

Fig 2. Kidney histopathology panel (Haematoxylin & Eosin) for the different treatments at 2, 6 and 18 days post-injury.

Gap length between injury edges is marked with a dark line. (L) Punch lesion (In) Perilesional inflammatory area, (Res) Residual scar. The chart indicates measurements in μm of the gap between lesion edges. (*) p<0.05 as compared to untreated animals (2 days); (‡), p<0.05 as compared to untreated animals (6 days); (†), p<0.05 as compared untreated animals (18 days).