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However, the same UV\u2010cross\u2010linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV\u2010cross\u2010linkable chitosan induced significant elevations in MIP\u20102 and TNF\u2010\u03b1 from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of <jats:italic>in vitro<\/jats:italic> cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. <jats:italic>in vivo<\/jats:italic>). \u00a9 2006 Wiley Periodicals, Inc. 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