Vocal Outcomes After COVR in Porcine Bilateral Vocal Fold Resection

Clinical Question

Does cell-based outer vocal fold replacement (COVR) with human adipose-derived stem cells lead to measurable recovery of vocal function in a preclinical setting?

Bottom Line

In a bilateral cordectomy porcine model, COVR implantation restored the median spectral energy frequency (Q50) to pre-operative levels by six months. It significantly changed other acoustic parameters, indicating partial phonatory recovery after severe vocal fold injury. Human stem cells persisted in the reconstructed vocal folds in seven of eight pigs at six months.

Background: Severe structural vocal fold injury, including oncologic resection or scarring, often produces permanent dysphonia because the lamina propria is replaced by disorganized collagen that fails to support normal vibration. Regenerative approaches such as COVR—a human adipose-derived stem cell construct in a fibrin scaffold—have shown improved biomechanics and scar prevention in rabbit models and demonstrated safety in pigs, but longitudinal functional vocal outcomes in large-animal models remain limited.

Study Design: Prospective large animal experimental study of eight Yucatan mini pigs undergoing bilateral European Laryngological Society type II cordectomy followed by immediate COVR implantation. Acoustic recordings were recorded pre-surgery and over six months post-surgery. Acoustic features (Q50, spectral flux, fundamental frequency, jitter, shimmer) were extracted in Python and analyzed using linear mixed-effects models and Wilcoxon rank-sum tests with Benjamini–Yekutieli correction. Fluorescent in situ hybridization (FISH) assessed human cell persistence.

Setting: UCLA David Geffen School of Medicine and affiliated centers, with acoustic and engineering collaboration at UCLA and phoniatrics support from University Hospital Erlangen.

Synopsis: Eight Yucatan mini pigs (four male, four female) underwent bilateral cordectomy with excision of epithelium and lamina propria from both vocal folds, followed by reconstruction using COVR implants anchored with sutures. Spontaneous vocalizations were recorded during standardized enclosure sessions before surgery and up to 27 weeks post-operatively; 291 pre-operative and 574 post-operative squeals met quality criteria for analysis. Five acoustic parameters were measured in this study: Q50 (median spectral energy frequency), spectral flux, fundamental frequency (F0), jitter, and shimmer, with time grouped into pre-operative, early, mid, and late post-operative phases. Population-level mixed effects modeling showed Q50 dropped significantly immediately after surgery (P< 0.001) but was no longer different from baseline by late post-operative recordings, suggesting recovery of spectral energy distribution. F0 increased significantly in the late post-operative period (P< 0.0001), while flux decreased mid- and late post-operatively with a small late effect size, and jitter and shimmer exhibited an early post-operative rise followed by partial normalization, reflecting evolving vibratory stability. FISH targeting human-specific GUCY2F demonstrated persistence of donor cells in seven of eight pigs, mainly in the lamina propria and occasionally in the epithelium. The authors conclude that COVR supports partial functional voice recovery after extensive bilateral mucosal resection, with ongoing extracellular matrix remodeling, and recommend one year of monitoring, AI-based acoustic analysis, and unilateral injury models with and without COVR to further define therapeutic impact.

Citation: Zhang K, et al. Vocal outcomes after cell-based outer vocal fold implant in porcine bilateral vocal fold resection. Laryngoscope. 2026. https://doi.org/10.1002/lary.70738.