Effect of "phase change" complex on postoperative adhesion prevention

J Surg Res. 2016 May 1;202(1):216-24. doi: 10.1016/j.jss.2015.12.033. Epub 2015 Dec 30.

Abstract

Background: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA).

Materials and methods: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination.

Results: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery.

Conclusions: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

Keywords: Adjustable; Chitosan; CsA; Degradable; Phase change; Postoperative adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants*
  • Animals
  • Biocompatible Materials / therapeutic use
  • Calcium Chloride / therapeutic use*
  • Chitosan / analogs & derivatives*
  • Chitosan / therapeutic use
  • Cyclosporine / therapeutic use*
  • Drug Combinations
  • Female
  • Immunosuppressive Agents / therapeutic use
  • Intestines / surgery
  • Male
  • Peritoneal Diseases / etiology
  • Peritoneal Diseases / prevention & control*
  • Postoperative Complications / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Single-Blind Method
  • Tissue Adhesions / etiology
  • Tissue Adhesions / prevention & control*
  • Treatment Outcome

Substances

  • Biocompatible Materials
  • Drug Combinations
  • Immunosuppressive Agents
  • O-carboxymethylchitosan
  • Cyclosporine
  • Chitosan
  • Calcium Chloride