Chitosan is made from chitin which is found in a large number of natural sources including crustaceans, insects, annelids and molluscs. Chitin is the most important polymer in the exoskeleton of these organisms. It has a low toxicity and is inert in the gastrointestinal system of mammals.
Chitosan is a commonly used product as a preservative and anti-microbial coating on fruits and vegetables for human consumption.
It is also used on seeds prior to planting, as a hydrating cosmetic product and as an additive to shampoos and toothpastes.25 25Muzzarelli RAA. Encyclopedia of Polymer Science and Engineering. 1990.,26 26Kurita K. Mar. Chitin and Chitosan: functional biopolymers from marine crustaceans. Biotechnol 2006; 8: 203:226
Chitosan has also been shown to prevent adhesions with multiple animal studies showing efficacy in adhesion reduction. 30 30Prevention 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. Costain DJ1, Kennedy R, Ciona C, McAlister VC, Lee TD. Surgery. 1997 Mar;121(3):314-9,31 31Prevention of experimental postoperative peritoneal adhesions by N,O-carboxymethyl chitosan. Kennedy R, Costain DJ, McAlister VC, Lee TD. Surgery. 1996 Nov;120(5):866-70.
Dextran is a polysaccharide made of D-glucose units linked predominantly by α-1,6 linkages. Before dextran can be cross-linked to the chitosan component, it must be activated. Reactive groups can be generated from the dextran by oxidation. The resulting activated dextran aldehyde can then be cross-linked to chitosan succinamide to form Chitogel.
To understand how the combination of chitosan succinamide and dextran aldehyde (Chitogel) works we must first look at the steps that occur in the wound healing process after endoscopic sinus surgery.
The physical barrier within the nose and the sinuses is formed by an intact mucous membrane and this protects the nose and sinuses from noxious insults, allergens, toxins, viruses and bacteria. During surgery, this natural barrier is disrupted and the body attempts to re-establish the barrier through the healing process.
The healing process starts with the formation of a blood clot. Within this blood clot there are factors that help the healing of a wound occur, including fibroblasts. Prolonged inflammation at this stage results in significant overstimulation of fibroblasts and significantly increased collagen formation with resultant adhesion formation.
Raw mucosal surfaces that are close to one another will stick together as fibroblasts migrate into the blood clot between these surfaces. The presence of a blood clot between surfaces greatly increases the risk of adhesion formation.
Two of the ways that Chitogel improves healing are that Chitogel has a significant anti-inflammatory action and Chitogel delays fibroblast migration 32 32The use of chitosan-dextran gel shows anti-inflammatory, antibiofilm, and antiproliferative properties in fibroblast cell culture. Paramasivan S1, Jones D, Baker L, Hanton L, Robinson S, Wormald PJ, Tan L. Am J Rhinol Allergy. 2014 Sep-Oct;28(5):361-5..
This dual effect of inhibiting inflammation and delaying fibroblast migration provides effective mechanisms for the anti-adhesion effect of Chitogel.33 33The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Valentine R, Athanasiadis T, Moratti S, Hanton L, Robinson S, Wormald PJ. Am J Rhinol Allergy. 2010 Jan-Feb;24(1):70-5.,34 34A blinded randomized controlled trial evaluating the efficacy of chitosan gel on ostial stenosis following endoscopic sinus surgery. Ngoc Ha T, Valentine R, Moratti S, Robinson S, Hanton L, Wormald PJ.Int Forum Allergy Rhinol. 2013 Jul;3(7):573-80. This is also thought to be Chitogel’s main mode of action in preserving the ostial patency of the sinus ostia. 35 35A blinded randomized controlled trial evaluating the efficacy of chitosan gel on ostial stenosis following endoscopic sinus surgery. Ngoc Ha T, Valentine R, Moratti S, Robinson S, Hanton L, Wormald PJ.Int Forum Allergy Rhinol. 2013 Jul;3(7):573-80.
Chitogel inhibits excessive blood clot formation, and the physical barrier that the gel creates once placed in the nose and the sinuses separates tissue surfaces to prevent fibroblasts migrating into coagulum and blood clot between mucosal surfaces.
Chitogel also improves the speed of wound epithelialization and studies have shown that this epithelium recovers its ciliated surface, as seen on electron microscopy, significantly faster than where no gel has been used.36 36Effects of a novel chitosan gel on mucosal wound healing following endoscopic sinus surgery in a sheep model of chronic rhinosinusitis. Athanasiadis T, Beule AG, Robinson BH, Robinson SR, Shi Z, Wormald PJ. Laryngoscope. 2008 Jun;118(6):1088-94. This indicates that although Chitogel delays fibroblast migration, it enhances epithelial migration and subsequent functionality thereby improving the healing time and functioning of the mucosa. This is also thought to contribute to the increased ostial patency when using Chitogel.37 37The efficacy of a novel budesonide chitosan gel on wound healing following endoscopic sinus surgery. Ha T, Valentine R, Moratti S, Hanton L, Robinson S, Wormald PJ. Int Forum Allergy Rhinol. 2018 Mar;8(3):435-443
Chitogel is a highly effective postoperative hydrogel nasal dressing that can be applied to sinuses after endoscopic sinus surgery and addresses a number of the traditional sinus surgery shortcomings:
Clinical results show that where Chitogel has been used post surgery, that compared to using no packing materials at 12 months post surgery, patients on average experienced the following:1 1Ha T, Valentine R, Moratti S, Hanton L, Robinson S, Wormald PJ. The efficacy of a novel budesonide chitosan gel on wound healing following endoscopic sinus surgery. Int Forum Allergy Rhinol. 2018 Mar;8(3):435-443.