Autologous fibroblasts for vocal scars and age‐related atrophy: A randomized clinical trial

Abstract

Objectives/Hypothesis: To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA). Study Design: Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial. Methods: ACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 10 7 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice. Results: Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed. Conclusions: In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP.

A Systematic Review on Surgical Treatments for Sulcus Vocalis and Vocal Fold Scar

“…The main characteristics of these 31 articles included in the analysis are seen in Table II Publication years of included articles ranged between 1993 and 2020. Four included studies (12.9%) were randomized controlled trials [25][26][27][28] (one of them including a placebo arm), one (3.2%) 9 was a quasi-experimental clinical trial, five (16.1%) 22,[35][36][37]41 were prospective cohorts, and the remaining (67.8%) were retrospective cohorts. Fifteen (48.4%) of the included studies had a high level of bias (MINORs score <11 points).…”

“…Three studies 14,19,21 included exclusively unilateral procedures, and five others only bilateral procedures. 20,26,27,33,34 Sixteen studies 9,16,17,20,[22][23][24][25]28,[32][33][34][35][38][39][40] (51.6%) included follow-ups greater than 6 months, and only in two studies 9,16 (6.5%) follow-up was longer than 1 year, for every patient. Of the 31 articles, 23 (74.2%) 9,13,17,21,24,25,[27][28][29][30][32][33][34][35][36]39,40 outlined self-reported outcomes, 24 (77.4%) 9,12,17,18,[21][22][23][24][25]…”

“…Some recent papers 33,34 seem to favor a sequential approach, with medialization techniques used as the first approach, based on the European Laryngeal Society recommendation for being the least invasive possible on the treatment of scar. 42 Outcomes that most consistently improve are selfreported outcomes, with few exceptions, 9,19,28 that include experimental techniques not reproduced in other studies. Stroboscopic outcomes are variable and many of the studies mention improvement, while not giving statistical analysis of its magnitude (as seen in Table II).…”

“…No complications were described with either of these products. Other attempted injection products included autologous fibroblasts, 28 glicocorticoids, 29 and collagen 30 with variable results, as stated in Table II.…”

Advances in regenerative medicine for otolaryngology/head and neck surgery

“…Four of the five patients showed objective and subjective improvements in voice quality and in mucosal wave by the study endpoint. This work was followed by a randomized, double blind, placebo controlled, multi-institutional, phase II trial 50. Fifteen patients with either vocal fold scar or atrophy received fibroblasts derived from the postauricular skin, and six patients received saline injections.…”