Tissue-Engineered Vocal Fold Mucosa Implantation in Rabbits.

Abstract

To assess phonatory function and wound healing of a tissue-engineered vocal fold mucosa (TE-VFM) in rabbits. An "artificial" vocal fold would be valuable for reconstructing refractory scars and resection defects, particularly one that uses readily available autologous cells and scaffold. This work implants a candidate TE-VFM after resecting native epithelium and lamina propria in rabbits. Prospective animal study. Research laboratory. Rabbit adipose-derived stem cells were isolated and cultured in three-dimensional fibrin scaffolds to form TE-VFM. Eight rabbits underwent laryngofissure, unilateral European Laryngologic Society type 2 cordectomy, and immediate reconstruction with TE-VFM. After 4 weeks, larynges were excised, phonated, and examined by histology. Uniform TE-VFM implants were created, with rabbit mesenchymal cells populated throughout fibrin hydrogels. Rabbits recovered uneventfully after implantation. Phonation was achieved in all, with mucosal waves evident at the implant site. Histology after 4 weeks showed resorbed fibrin matrix, continuous epithelium, and mildly increased collagen relative to contralateral unoperated vocal folds. Elastic fiber appearance was highly variable. Inflammatory cell infiltrate was limited to animals receiving sex-mismatched implants. TE-VFMs were successfully implanted into 8 rabbits, with minor evidence of scar formation and immune reaction. Vibration was preserved 4 weeks after resecting and reconstructing the complete vocal fold cover layer. Further studies will investigate the mechanism and durability of improvement. TE-VFM with autologous cells is a promising new approach for vocal fold reconstruction.