Amniotic Fluid as a Potential Treatment for Vocal Fold Scar in a Rabbit Model

J Voice. 2025 Jan 3:S0892-1997(24)00445-4. doi: 10.1016/j.jvoice.2024.12.015. Online ahead of print.

Abstract

Objectives/hypothesis: Vocal fold (VF) injury and chronic inflammation can progress to scarring, which is notoriously difficult to treat. Human amniotic fluid (AF) has potential for VF wound healing in a rabbit model, and we hypothesized that AF would demonstrate wound healing properties superior to hyaluronic acid (HA) over time.

Study design: Randomized, controlled trial.

Methods: In this pilot study, 60 New Zealand white rabbits (10 rabbits in each of six groups) received unilateral VF biopsy and immediate injection treatment of AF, HA, or saline (SA). The contralateral VF served as an uninjured control. Rabbits were sacrificed and VFs removed at 4 or 10 weeks postinjury. Rheology and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were employed to assess viscoelastic properties and inflammation, respectively.

Results: Rheology differences were seen between four and 10 weeks postinjury in treatment groups but not in controls. Values for the AF treatment group differed from the SA and HA groups at week 10 (elastic P = 0.0002, viscous P < 0.0001). RT-qPCR: AF and HA had higher levels of inflammatory cytokines than SA at week 4 [TNFα: SA4 < HA4 (P = 0.0086), SA4 < AF4 (P = 0.0112)]. Presumptive inflammation was still present at 10 weeks in all treatment groups [IL-1β: AF control < AF (P = 0.0002), SA control < SA (P = 0.0212); IL-6: HA control < HA (P = 0.0312)]. AF demonstrated reduced inflammation at 10 weeks compared with SA [IL-6: SA > AF (P = 0.0141)]. AF was the only treatment group that had significant reductions in inflammation at 10 versus 4 weeks [IL-1β: AF4 > AF10 (P = 0.0249)].

Conclusions: The main finding from this pilot study was that AF demonstrated wound healing effects over time compared with HA and SA by reducing inflammation and improving VF viscoelastic properties. Continued research to further investigate the use of AF in VF wound healing over longer periods of time is necessary before translation to human VFs.

Keywords: Vocal fold scar—Amniotic fluid—Hyaluronic acid—Rabbit.