Vocal Outcomes After Cell-Based Outer Vocal Fold Implant in Porcine Bilateral Vocal Fold Resection

Cell-based outer vocal fold replacement (COVR) consists of human adipose-derived stem cells and is a potential treatment for severe vocal fold injury. Prior rabbit studies demonstrated enhanced wound healing and COVR's safety in pigs. Building on prior work defining pig-specific acoustic parameters, this study evaluates phonatory recovery and establishes quantitative voice assessment frameworks following bilateral cordectomy and COVR implantation in a large animal model.

COVR implantation was performed in eight Yucatan mini-pigs after bilateral vocal fold resection. Functional voice recovery was tracked, with spontaneous vocalizations recorded pre- and post-surgery for up to 6 months. Pig squeals were extracted using Python, manually verified, and nonrepresentative sounds excluded. Acoustic features including Q50 (median frequency of spectral energy), flux (rate of spectral energy change), F0 (fundamental frequency), jitter (period perturbation), and shimmer (amplitude perturbation) were analyzed using linear mixed-effect models and Wilcoxon rank sum test with Benjamini-Yekutieli correction. After 6 months, larynges were harvested and human cells were sought via fluorescent in situ hybridization.

Q50 significantly decreased immediately postoperatively (p < 0.001) and returned to preoperative range by 6 months, while F0 and flux changed modestly over time. Human cells persisted in 7 of the 8 subjects.

COVR implantation improved key nonperiodic acoustic parameters 6 months after extensive laryngeal injury in pigs. Implanted cells were detected after 6 months. Future work includes one-year monitoring to assess long-term voice recovery and extracellular matrix remodeling, artificial intelligence integration for expanded acoustic analysis, and a unilateral injury model comparing control cordectomy alone versus COVR reconstruction.

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