A chitosan-based sinus sealant for reduction of adhesion formation in rabbit and sheep models

Abstract

Objective: Chronic sinusitis is the most prevalent chronic disease in the United States in adults aged 18 to 44 years, with approximately 250,000 operations performed annually. Although often successful, sinus surgery fails in greater than 15% of patients. Adhesion formation is a common complication and cause for subsequent revision surgery. Here, the authors evaluate a sprayable chitosan/starch-based sinus sealant and demonstrate its ability to reduce adhesion formation both in vitro and in 2 animal models.

Study design: Randomized, controlled, animal trials.

Setting: Academic medical center (fibroblast experiments) and animal laboratories (sheep and rabbit studies).

Subjects and methods: This sinus sealant was applied to human cultured fibroblasts obtained from surgically removed polyps to examine its ability to inhibit fibroblast migration and proliferation. The sinus sealant was applied to New Zealand White rabbits (n = 20) in an established cecal-sidewall abrasion model and to sheep (n = 10) in a sinus surgical adhesion model to examine its ability to reduce adhesion formation.

Results: This sinus sealant inhibited migration and proliferation of human cultured fibroblasts and reduced the total adhesion score from 4.9 to 0.3 for a total reduction of 94% (95th percentile confidence interval [CI], 78%, 100%; P < .001) in a well-established rabbit cecal-sidewall model commonly used for adhesion testing. Moreover, this sealant reduced adhesion formation from 80% to 10% for a total reduction of 70% (95th percentile CI, 57%, 93%; P = .003) in a sheep sinus adhesion surgical model.

Conclusion: This chitosan-based sealant demonstrates promise for reducing adhesion formation in sinus surgery.

Figure 1

Biochemical formulation of chitosan, the active compound used in this sealant. The chitosan active compound was selected for its potential as an antiadhesive during sinus surgery.

Figure 2

Chitosan was compounded with a starch-based gel to make the final preparation.

Figure 3

A spray medical device was then developed to allow precise delivery of the compound to sinus cavities.

Figure 4

Human nasal polyp fibroblast migration and proliferation model. (A) Dose-response inhibition of fibroblast migration and proliferation by chitosan. (B) Inhibition of fibroblast migration and proliferation by chitosan-based sealant. Microscopy images at 0 and 72 hours of untreated at 0 (C, E) and 72 (D, F) hours and treated wounded fibroblast monolayers, respectively, show complete inhibition of migration and proliferation in sealant-treated fibroblasts.

Figure 5

Rabbit cecal and sidewall adhesion model. (A) Sealant treatment of wounds resulted in significantly lower adhesion scores, which reduced the calculated total adhesion score by 94% compared with untreated controls. *P < .001. (B) Control rabbit after wounding. (C) Large adhesion formed 14 days after surgery. (D) Rabbit treated with chitosan-based sealant. (E) Lack of adhesion formation 14 days after surgery.

Figure 6

Experimental sheep sinus surgical model. Sealant treatment reduced adhesion formation by 70%. Black arrows indicate adhesions in the untreated sides of the sheep. (A) A control sheep nasal cavity showing large adhesion formation 18 days after surgery. (B) A sheep nasal cavity treated with chitosan-based sealant showing no adhesion formation. (C) Closeup of a nasal cavity showing two adhesions in a control animal 18 days after surgery. (D) Closeup of a nasal cavity treated with chitosan-based sealant showing no adhesion formation.