The effects of cryotherapy on vocal fold healing in a rabbit model

Abstract

Objectives/Hypothesis Cryotherapy has been shown to be a scarless treatment modality for dermal lesions; however, there are limited data addressing the effect of cryotherapy on vocal fold tissue. The aim of this study was to clarify the effectiveness of cryotherapy for prevention of postsurgical vocal fold scarring. Study Design Prospective animal study in rabbits. Methods The lamina propria of 20 rabbit vocal folds was bilaterally stripped, followed by randomized unilateral cryotherapy. Five larynges were harvested for real‐time polymerase chain reaction (RT‐PCR) analysis at 1 day, 3 days, and 7 days postinjury. The remaining five were harvested for histologic analysis at 3 months. Images of the healing phase were recorded by laryngoscopy. Analyses of RT‐PCR for cyclooxygenase (COX)‐2, interleukin (IL)‐6, collagen I, collagen III, matrix metallopeptidase 1 (MMP1), transforming growth factor β (TGFβ1), α smooth muscle actin (α‐SMA), and hyaluronan synthase 1 (HAS1) were completed. Histological samples were completed for collagen and hyaluronic acid analysis. Results RT‐PCR results revealed that higher expressions of HAS1 and MMP1 and lower expressions of COX‐2, IL‐6, collagen I, collagen III, TGFβ1, and α‐SMA were observed, and histological examination showed significantly increased hyaluronic acid, decreased deposition, and more organized configuration of collagen in injury with the cryotherapy cohort compared with the injury cohort. Conclusions Cryotherapy can inhibit the inflammatory reaction and simulate a fetal healing environment in extracellular matrix synthesis to regenerate vocal fold tissue with less fibrosis. Histological results showed that cryotherapy achieves a mature healing result with less scar, which tends to return to normal. In summary, the findings of this study suggest that administration of cryotherapy at the time of injury has the potential to minimize vocal fold scarring. Level of Evidence NA Laryngoscope, 129:E151–E157, 2019

The Role of Cytokines in Modulating Vocal Fold Fibrosis: A Contemporary Review

“…Dysregulation of TGF‐β and its isoforms following VF injury is one of the primary mechanisms underlying the development of fibrosis 27,28 . Many fibrotic conditions are characterized by sustained and excessive TGF‐β signaling, resulting in altered ECM metabolism and fibroblast–myofibroblast differentiation 29,30 .…”

“…Dysregulation of TGF-β and its isoforms following VF injury is one of the primary mechanisms underlying the development of fibrosis. 27,28 Many fibrotic conditions are characterized by sustained and excessive TGF-β signaling, resulting in altered ECM metabolism and fibroblast-myofibroblast differentiation. 29,30 In the early stages of the wound-healing process, TGF-β modulates complex interactions among fibroblasts, inflammatory cells, and TGF-β signaling.…”

Phonosurgery: A review of current methodologies

“…82 Because scarring is the primary cause of poor postoperative voice quality, cryotherapy's potential to produce minimal scarring yields high potential as a treatment for laryngeal lesions. Gong et al 15 found that cryotherapy in a rabbit model simulates an environment similar to that of the fetal wound-healing environment, which is characterized by minimal inflammation, rapid re-epithelialization, and reduced collagen formation. Knott et al 84 found both reduced collagen formation with more organized structure after application of cryotherapy, along with decreased keratinization.…”

Radiation-induced neuropathies in head and neck cancer: prevention and treatment modalities

“…The use of steroids, proton pump inhibitors and TNF-α have been advocated [195]. Moreover, cryotherapy promoted regeneration and reduced inflammation and fibrosis in larynxes of rabbits [196]. Thereafter, all of the abovementioned treatments should be investigated in radiationinduced dysphonia context.…”