Non-clinical safety of novel cross-linked chondroitin sulfate (SI-449) as an anti-adhesion barrier for abdominal and pelvic surgeries

Abstract

Postoperative adhesions result from abnormal tissue repair and most frequently occur in patients following abdominal and pelvic surgeries. Prevention of adhesion formation, including the use of anti-adhesion barriers during surgery, is considered the most effective clinical strategy for postoperative adhesions. However, no commercial product is commonly used worldwide because of its insufficient efficacy, complexity, and difficulty of use. We developed a new anti-adhesion barrier using novel biomaterial (SI-449), a cross-linked chondroitin sulfate, in an easy-to-apply powder form. Our previous study using animal models showed that the anti-adhesion efficacy of SI-449 was superior to that of an existing product. In this study, the safety of SI-449 was evaluated based on the results of systemic toxicity tests in rats after intraperitoneal application and a wound healing test in laparotomized rats to mimic its clinical use in abdominal and pelvic surgeries. In the systemic toxicity test, minimal and transient hematological changes and muscular regeneration in the abdominal wall and ileum were observed and were considered to be related to systemic toxicity or local irritation due to SI-449. However, these findings were within the safety margin and not associated with serious toxicity. Other changes were considered physiological reactions to SI-449 or its degradants. In the wound healing test, SI-449 was found to have no effect on the healing of the incisional abdominal wall. In conclusion, the non-clinical safety of SI-449 was confirmed, and this novel biomaterial is expected to be used as an anti-adhesion barrier in abdominal and pelvic surgeries.