Thermoresponsive gel delivery of caffeic acid promotes healing in a rat nasal septal perforation model

Abstract

Background: Nasal septal perforations (NSPs) are a challenging clinical problem due to impaired healing under constant airflow, dryness, and microbial exposure. Adjuncts that enhance mucosal regeneration and extracellular matrix activity are needed.

Objectives: This study evaluated whether topical caffeic acid (CA) delivered in a thermoresponsive Pluronic F127 gel improves histopathological and macroscopic healing in a rat NSP model.

Material and methods: Nineteen male Sprague Dawley rats were randomly assigned to control (n = 8) or CA (n = 11) groups. A standardized full-thickness septal perforation (∼2 mm) was surgically created. Controls received intranasal saline, while the CA group received 0.2 mL CA-loaded Pluronic F127 gel once daily for 14 days. Histopathological parameters (epithelial regeneration, degeneration, fibroblast density, collagen density, angiogenesis, inflammation) were scored on a 0-3 scale. Macroscopic closure was also evaluated. Fisher's exact test was applied (p < 0.05).

Results: CA significantly increased epithelial regeneration (p = 0.005), fibroblast density (p = 0.014), and collagen density (p = 0.018), while reducing epithelial degeneration (p < 0.001). Angiogenesis and inflammation showed favorable trends. Macroscopic closure improved but was not statistically significant (p = 0.101).

Conclusions and significance: Topical CA in a thermoresponsive gel enhanced mucosal repair and extracellular matrix activity in a rat NSP model, supporting its potential as a therapeutic adjunct in septal perforation management.

Keywords: Nasal septal perforation; Pluronic F127; caffeic acid; epithelial regeneration; thermoresponsive gel; wound healing.