Effects of a Novel Chitosan Gel on Mucosal Wound Healing Following Endoscopic Sinus Surgery in a Sheep Model of Chronic Rhinosinusitis

Abstract

Postoperative bleeding and adhesion formation remain the two major problems after endoscopic sinus surgery (ESS). This study investigates the effect on adhesion formation and wound healing in a sheep model of chronic sinusitis of three topical agents: recombinant tissue factor (rTF, Dade Innovin, Marburg, Germany), poly-ethylene glycol (SprayGel, Confluent Surgical, Waltham, MA), and a novel chitosan-dextran derivative gel (CD, Department of Chemistry, University of Otago, Dunedin, New Zealand). Twenty sheep with chronic sinusitis underwent ESS with standardized mucosal injuries created on the lateral nasal wall and the ethmoid region. Injured areas were divided into four groups, and one of the three agents or control (no treatment) was randomly applied. The presence and severity of adhesions were noted and the healing was evaluated by taking brushings for ciliary beat frequency and biopsies of the injured regions at day 28, 56, 84, and 112 post initial surgery. The biopsy specimens were assessed for re-epithelialisation using light microscopy and scanning electron microscopy for reciliation. The cytobrush specimens assessed cilial function by measuring ciliary beat frequency. CD significantly decreased lateral nasal wall and ethmoidal adhesions compared to tissue factor at all time points (5% vs. 25%, and 0 vs. 50%, respectively). There was a noticeable trend toward decreased adhesions on the lateral nasal wall and ethmoids in the SprayGel group (10% and 14%) and the CD group (10% and 0%) compared to controls (15% and 40%). The CD group had a significantly greater percentage of re-epithelialisation at day 28 and day 84 compared to the rTF group (70% vs. 33%, P < .001; 84.5% vs. 61%, P < 0.05). At day 28, the CD group was significantly more ciliated than control (62% vs. 31%, P < .01) and than rTF (62% vs. 23%, P < .001). This difference between CD and rTF reciliation remained significant at day 56 (67% vs. 40%, P < .05). In addition, the mean cilial grade for CD at day 112 was significantly better than control (1.9 vs. 2.7, P < .05). In the sheep model of chronic sinusitis, CD significantly improves microscopic wound healing and reduces adhesion formation after ESS.