Expanding Hydrophobically Modified Chitosan Foam for Internal Surgical Hemostasis: Safety Evaluation in a Murine Model

J Surg Res. 2019 Jul;239:269-277. doi: 10.1016/j.jss.2019.01.060. Epub 2019 Mar 16.

Abstract

Background: A novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter).

Methods: Sixty-four Sprague-Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed.

Results: All animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS.

Conclusions: The internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate.

Keywords: Biodegradation; Chitosan; Fibrin sealant; Foam; Hemostasis; in vivo study.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Loss, Surgical / prevention & control*
  • Chitosan / administration & dosage*
  • Chitosan / adverse effects
  • Chitosan / chemistry
  • Disease Models, Animal
  • Fibrin Tissue Adhesive / administration & dosage
  • Hemostasis, Surgical / methods*
  • Hemostatics / administration & dosage*
  • Hemostatics / adverse effects
  • Hemostatics / chemistry
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Liver / surgery
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Fibrin Tissue Adhesive
  • Hemostatics
  • Chitosan