Quantifying vocal fold wound‐healing biomechanical property changes

Abstract

OBJECTIVES: Development of novel vocal fold (VF) therapeutics is limited by a lack of standardized, meaningful outcomes. We hypothesize that automated microindentation-based VF biomechanical property mapping matched to histology permits quantitative assessment. STUDY DESIGN: Ex vivo. METHODS: Twelve anesthetized New Zealand white rabbits underwent endoscopic right VF injury. Larynges were harvested/bisected day 7, 30, or 60 (n = 4/group), with four uninjured controls. Biomechanical measurements (normal force, structural stiffness, and displacement at 1.96 mN) were calculated using automated microindentation mapping (0.3 mm depth, 1.2 mm/s, 2 mm spherical indenter) with a grid overlay (>50 locations weighted toward VF edge, separated into 14 zones). Specimens were marked/fixed/sectioned, and slides matched to measurement points. RESULTS: In the injury zone, normal force/structural stiffness (mean, standard deviation [SD]/mean, SD) increased from uninjured (2.2 mN, 0.64/7.4 mN/mm, 2.14) and day 7 (2.7 mN, 0.75/9.0 mN/mm, 2.49) to day 30 (4.3 mN, 2.11/14.2 mN/mm, 7.05) and decreased at 60 days (2.7 mN, 0.77/9.1 mN/mm, 2.58). VF displacement decreased from control (0.28 mm, 0.05) and day 7 (0.26 mm, 0.05) to day 30 (0.20 mm, 0.05), increasing at day 60 (0.25 mm, 0.06). A one-way ANOVA was significant; Tukey's post hoc test confirmed day-30 samples differed from other groups (P < 0.05), consistent across adjacent zones. Zones far from injury remained similar across groups (P = 0.143 to 0.551). These measurements matched qualitative histologic variations. CONCLUSION: Quantifiable VF biomechanical properties can be linked to histology. This technological approach is the first to simultaneously correlate functional biomechanics with histology and is ideal for future preclinical studies. LEVEL OF EVIDENCE: NA Laryngoscope, 130:454-459, 2020.