Introduction: Adhesion formation remains a frequent complication after abdominal surgery[1]. Crucial steps in serosal wound healing and adhesion formation represent inflammation, fibrin exsudation and fibrous organisation of fibrin bands[2]. Today, the physical separation of damaged serosa represents the leading strategy in adhesion prevention[3]. SupraSeal®, a promising barrier based on poly-D,L-lactide-e-caprolactone-trimethylene carbonate, was shown to be effective in the prevention of peritoneal adhesions[4]. However, no studies exist regarding the time course of the tissue reaction after implantation of this material. The present study presents an investigation of the tissue reaction after 2, 4 and 8 days in an animal model.
Materials and Methods: After bipolar electrocoagulation and induced ischemia Wistar rats were treated (n=20) or not treated (n=20) with SupraSeal®. After 2 (n=7), 4 (n=7) and 8 (n=6) days the animals were killed and the peritoneal wall with the barrier-membrane including surrounding peritoneum was explanted and processed by standard methods for histological evaluation. Via haematoxylin & eosin, chloracetate esterase and elastica van Gieson staining as well as immunohistological evaluation of CD68-positive macrophages the inflammatory response, extent of fibrosis, macrophage infiltration and the amount of fibrin were scored (0 = no reaction/infiltration, 1 = mild reaction/infiltration, 2 = moderate reaction/infiltration, 3 = severe reaction/infiltration). In addition, the extent of adhesion formation was macroscopically assessed.
Results: Macroscopically, mild adhesion formation occurred in the control (1.86) two days postoperatively, but none in the barrier group (0.00). Inflammation was moderate in the control (1.67) and mild in the barrier group (1.29). Both groups revealed moderate macrophage infiltration (control: 1.67, barrier: 2.00) and a narrow fibrosis band. Fibrin exudation was minimal in both groups (control: 0.67, barrier: 1.29). After four days, there was a moderate amount of adhesion formation in the control (1.83) and no adhesions in the barrier group (0.33). The inflammatory response was moderate in the control (1.71) and mild in the barrier group (1.40), whereas macrophage infiltration was mild in the control (0.71) and moderate in the barrier group (1.6). Both groups revealed a narrow adhesion band (control: 1.14, barrier: 1.20). Fibrin exudation was negligible to absent in both groups (control: 0.29, barrier: 0.00). Eight days after treatment, both groups revealed macroscopically severe adhesion formation (control: 2.71, barrier: 2.00). Moderate inflammation was detected in both groups (control: 2.17, barrier: 1.83) as well as a mild macrophage infiltration (control: 0.67, barrier: 1.2). A moderate fibrosis band was present in the control and a narrow band in the barrier group. No fibrin was detectable in either group (both: 0.00)
Discussion and Conclusion: For the first time, the histomorphological effects of SupraSeal® on adhesion formation over time were analyzed. The results gave interesting insights into the early stage of peritoneal wound healing and the initial processes in adhesion formation. Especially the findings after two and four days illustrate the importance of the early stage of peritoneal healing. At these two time points the amount of fibrin differs between the two groups. Fibrin is described as “minimal” in the median in both groups on day two, but the absolute count reveals an obvious difference between the groups (control: 0.67 vs barrier: 1.29). On day four, however, fibrin has completely disappeared in the barrier group (0.00) but was still slightly present in the control (0.29). Since postoperative adhesions originate by the organization of fibrin bands which occur between wounded and surrounding peritoneum (1, 2), the early elimination of fibrin might play a crucial role in adhesion formation and offer an interesting target for the prevention of postoperative adhesions.
References:
[1] Brochhausen C et al. J Biomed Mater Res A 98: 143-56, 2011
[2] Brochhausen C et al. J Gastrointest Surg 16 (6): 1256-74, 2012
[3] Brochhausen C et al. J Mater Sci Mater Med 23 (8): 1931-9, 2012
[4] Rajab TK et al. Surgery 145 (2): 196-201, 2009