Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: Examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing

Abstract

Background. Adhesion formation after operation can result in major complications. We have previously demonstrated that N,O-carboxymethyl chitosan (NOCC) is an effective inhibitor of postsurgical peritoneal adhesion formation. However, the optimal form of NOCC (i.e., cross-linked gel versus solution), as well as the best time of administration for optimal reduction in adhesion development, was not investigated. In addition, because adhesion formation and normal wound healing are related events and weakening of wound healing would be a serious drawback to the use of NOCC clinically, we wished to assess the effect of NOCC on the healing of surgical incisions. Methods. Three surgical models were used: (1) an abdominal aortic anastomosis, (2) a large bowel anastomosis, and (3) an abdominal skin incision. In the first model Sprague-Dawley rats received an abdominal aortic transection and repair. NOCC solution or gel was administered at different time points throughout the procedure. Control and NOCC-treated animals were killed 14 days after operation. The condition of the anastomosed vessel was examined, and adhesion frequency and intensity in the abdomen were scored. In the second model Sprague-Dawley rats underwent large bowel transection and repair. Control and NOCC-treated animals were killed on postoperative days 4, 7, and 14, and strength of repair was assessed by removal of the large bowel and measurement of the bursting strength of the repaired incision. In the third model rats received an abdominal incision and were immediately closed. Control and NOCC-treated animals were killed 14 days after operation, and the skin tensile strength of the wound was measured with a tensiometer. Results. In all three models studied, NOCC treatment did not adversely affect the strength of the repaired incision. NOCC solution administered before operation did not greatly reduce adhesion formation, whereas the delivery of both NOCC gel and solution after operation was most efficacious. Conclusions. The administration of both NOCC gel and solution after operation is most efficacious, and NOCC does not compromise postsurgical healing in rats at doses that prevent peritoneal adhesion formation.