Development of an Animal Model for Wound Healing in Chronic Rhinosinusitis

Objective: To develop a model for sinonasal wounding and evaluation during healing in mice with chronic eosinophilic inflammation. Design: Exploratory controlled study in which chronic eosinophilic nasal and sinus inflammation was established in mice followed by wounding of the sinonasal cavity. Histologic features and gene expression were then studied. Setting: University of Utah Center for Comparative Medicine. Subjects: Chronic eosinophilic inflammation was established in mice. They were then wounded and humanely killed at days 3, 7, and 14 after wounding. Main Outcome Measures: Inflammation was assayed by light microscopic examination. Polymerase chain reaction analysis of transforming growth factor-beta 1b, insulinlike growth factor (IGF)-1, matrix metalloproteinase (MMP)-7, MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), and prostaglandin E receptor EP4 expression was performed as well. Uninflamed mice were wounded and examined using the same protocol. Results: Chronically inflamed mice showed higher histologic inflammatory scores before and after wounding. Expression of IGF-1, TIMP-1, and MMP-9 was also higher prior to wounding and during healing. Continued stimulation appears necessary for the chronic eosinophilic inflammation to persist. Conclusions: We successfully constructed a model in which wound healing in a setting of chronic eosinophilic inflammation can be studied. In this exploratory pilot, we demonstrated the feasibility of reproducibly wounding the sinonasal cavity of chronically inflamed mice and examining histologic and gene expression effects of the inflammatory response after wounding.