Effect of pirfenidone injection on ferret vocal fold scars: A preliminary in vivo study

Abstract

Objectives This study examined the antifibrotic effect of pirfenidone (PFD), which has received regulatory approval in the United States and Japan for treatment of idiopathic pulmonary fibrosis, on the scarred ferret vocal fold (VF) in vivo. Methods Eight male ferrets were divided into two groups: saline and PFD. All animals underwent unilateral scarring under anesthesia. The right VF was electrocauterized with ablation of the entire lamina propria. PFD (1.0 mg/mL) or saline injections into right‐side scarred VFs were performed (under an operating microscope) 4 weeks later. After an additional 4 weeks, the larynges were harvested for histological analysis. Prior to harvesting, the ferrets were re‐anesthetized, and the VFs were observed and recorded using a rigid video laryngoscope. We immunohistochemically evaluated the expression of collagen types I and III, alpha‐smooth muscle actin (α‐SMA), and fibronectin in the entire lamina propria. We compared the affected areas (calculated using ImageJ software) between the treated (right) and untreated (left) sides within the same animals and between groups. Results Collagen type I (P = 0.0021) and α‐SMA (P = 0.0021) expression levels were lower in the PFD group, but the collagen type III and fibronectin levels did not differ significantly between the two groups. Conclusion PFD injection into the scarred VF is a potentially promising novel antifibrotic treatment. Level of Evidence NA Laryngoscope, 130:726–731, 2020

Hyaluronan Hydrogels for the Local Delivery of Mesenchymal Stromal Cells to the Injured Vocal Fold

“…Hydrogel-based delivery of the anti-fibrotic growth factor, HGF, has also been reported in a canine model of VF injury, with data indicating that 3 months after treatment there was reduced PTP, decreased type I collagen, improved mucosal wave excursion and increased HA abundance compared to the saline treated control group (179). Similarly, pirfenidone delivery has also been considered, exhibiting both anti-inflammatory and anti-fibrotic effects in vivo and in vitro (180). New approaches for the treatment of chronic scarring are also being developed using PGE2.…”

Current approaches to management of vocal fold scar

“…Unfortunately, a dose-dependent cytotoxicity was identified which may limit the use of MMC in early VF wound healing [12]. Pirfenidone is approved for idiopathic pulmonary fibrosis treatment and has been explored in animal models of VF scar [13]. Pirfenidone applied to an injured ferret VF resulted in a reduction in collagen type I and aSMA expression but did not modify the expression of collagen type III or fibronectin, suggesting benefit may depend on the exact balance of cytokine expression in the wound bed [13].…”