Regulation of Macrophage Behavior to Prevent Vocal Fold Fibrosis

Abstract

A 2021 epidemiological study in Japan revealed that iatrogenic causes represent the most prevalent etiology of vocal-fold scarring. Owing to the absence of validated therapeutic modalities, over half of the cases remain untreated. Vocal fold surgery has been identified as a significant factor contributing to the development of scarring, with evidence of scarring being present in all cases. These findings underscore the need for a more comprehensive understanding of the underlying pathology and the advancement of preventive treatments. Research on tissue regeneration and fibrosis in various organs has been ongoing for several years. Single-cell analyses have recently identified numerous cellular players and networks involved in fibrosis, marking a new era in the field of fibrosis research. In particular, interactions between fibroblasts and macrophages play a critical role in both tissue regeneration and fibrosis. In the context of vocal folds, co-culture experiments have demonstrated that these interactions promote fibrosis, thereby underscoring the need for macrophage-targeted therapeutic strategies. Following vocal fold injury, we observed transient infiltration of inflammatory macrophages. We herein report our efforts to enhance wound healing by promoting the transition from inflammatory to reparative macrophage polarization.