Current research approaches employ traditional tissue engineering strategies to promote vocal fold (VF) tissue regeneration, whereas recent novel advances seek to use principles of developmental biology to guide tissue generation by mimicking native developmental cues, causing tissue or allogenic/autologous progenitor cells to undergo the regeneration process. To address the paucity of data to direct VF differentiation and subsequent new tissue formation, we characterize structure-proliferation relationships and tissue elastic moduli over embryonic development using a murine model. Growth, cell proliferation, and tissue biomechanics were taken at E13.5, E15.5, E16.5, E18.5, P0, and adult time points. Quadratic growth patterns were found in larynx length, maximum transverse diameter, outer dorsoventral diameter, and VF thickness; internal VF length was found to mature linearly. Cell proliferation measured with EdU in the coronal and transverse planes of the VFs was found to decrease with increasing age. Exploiting atomic force microscopy, we measured significant differences in tissue stiffness across all time points except between E13.5 and E15.5. Taken together, our results indicate that as the VF mature and develop quadratically, there is a concomitant tissue stiffness increase. Greater gains in biomechanical stiffness at later prenatal stages, correlated with reduced cell proliferation, suggest that extracellular matrix deposition may be responsible for VF thickening and increased biomechanical function, and that the onset of biomechanical loading (breathing) may also contribute to increased stiffness. These data provide a profile of VF biomechanical and growth properties that can guide the development of biomechanically-relevant scaffolds and progenitor cell differentiation for VF tissue regeneration.
Objective: To delineate the relationship between patient and parent-reported quality of life (QOL) ratings and perceptual characteristics of speech assigned by a speech-language pathologist (SLP) in children with repaired cleft palate. Design: Prospective. Setting: Academic Children’s Hospital. Participants: This population-based sample included children, aged 3 to 18 with a history of repaired cleft palate, and their parents. Intervention: Participants completed the Velopharyngeal Insufficiency Effects on Life Outcomes Questionnaire (VELO). Children’s speech was judged perceptually by an expert SLP using the Pittsburgh Weighted Speech Scale (PWSS). Main Outcome Measure(s): Velopharyngeal Insufficiency Effects on Life Outcomes questionnaire assessed participant and parent perceptions of impact of velopharyngeal function on QOL. Pittsburgh Weighted Speech Scale assessed nasal emissions, facial grimacing, nasality, quality of phonation, and articulation. Results: Enrollment included 48 participant parent dyads. Overall, participants reported high QOL scores within the 95% CI with children reporting slightly better yet not significantly different QOL (86.27 ± 8.96) compared to their parents (81.81 ± 15.2). Children received an average score of 1.38 ± 1.96 on the PWSS corresponding to borderline velopharyngeal competence. A significant moderate negative correlation was found between PWSS total score and parent VELO total score (r = −0.51103, P = .0002). Mild–moderate significant negative correlations were measured between PWSS total and the 5 subscales of the VELO. No significant correlations were measured between PWSS and child VELO total responses or between total scores and subscales. Conclusions: Results suggest that as perceptual analysis of speech improves, overall QOL improves moderately.
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