Abstract

Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly undesirable. We have developed a novel mouse peritoneal strip ex vivo adhesion model which may serve to bridge the gap between single cell culture systems and in vivo animal drug testing for the assessment of potential anti-adhesion agents, and study of causality of the process. We investigated the optimal conditions for adhesion formation with mouse peritoneal tissue strips by modifying an existing ex vivo rat model of peritoneal adhesions. We assessed the impact of the following conditions on the formation of adhesions: contact pressure, abrasions, and the presence of clotted blood. Macroscopic adhesions were detected in all mouse peritoneal strips exposed to specific conditions, namely abrasions and clotted blood, where peritoneal surfaces were kept in contact with pressure using cotton gauze in a tissue cassette. Adhesions were confirmed microscopically. Interestingly, connexin 43, a gap junction protein, was found to be upregulated at sites of adhesions. Key features of this model were the use of padding the abraded tissue with gauze and the use of a standardised volume of clotted blood. Using this model, peritoneal strips cultured with clotted blood between abraded surfaces were found to reproducibly develop adhesion bands at 72h. Our goal is to develop a model that can be used in genetically modified mice in order to dissect out the role of particular genes in adhesion formation and to test drugs to prevent adhesion formation.

Highlights

  • Post-surgical peritoneal adhesions pose a considerable risk in modern-day procedures

  • We investigated the optimal conditions for adhesion formation with mouse peritoneal tissue strips by modifying an existing ex vivo rat model of peritoneal adhesions

  • We found that the combination of contact between peritoneal surface, abrasion trauma, and clotted blood was essential for adhesion development in this mouse ex vivo adhesion model

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Summary

Introduction

Post-surgical peritoneal adhesions pose a considerable risk in modern-day procedures. Peritoneal and pelvic adhesions are a major cause of infertility [1]. Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still plague even the most experienced surgeons. Various experimental models can be employed/studied to assess the efficacy of anti-adhesion agents in preventing post-surgical peritoneal adhesions. The models are inherently variable and require large numbers of animals per treatment group to ensure the reliability of the results. In addition to this are the requirements for calibration of each model, testing of multiple treatments and the comparison of dose-responses, which all further increase the number of animals used and the related costs

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