elastin and Voice-Disorders

Elastic fibers are large, complex, and surprisingly poorly understood extracellular matrix macromolecules. The elastin fiber, generated from a single human gene--elastin, is a self assembling integral protein that endows critical mechanical proprieties to elastic tissues and organs such as the skin, lungs, and arteries. The biology of elastic fibers is complex because they have multiple components, a tightly regulated developmental deposition, a multistep hierarchical assembly, and unique biomechanical functions. Elastin is present in vocal folds, where it plays a pivotal role in the quality of phonation. This review article provides an overview of the genesis of elastin and its wide-ranging structure and function. Specific distribution within the vocal fold lamina propria across the lifespan in normal and pathological states and its contribution to vocal fold biomechanics will be examined. Elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. The properties of various elastin-based materials will be discussed and their current and future applications evaluated. A new level of understanding of the biomechanical properties of vocal fold elastin composites and their molecular basis should lead to new strategies for elastic fiber repair and regeneration in aging and disease.

Topics: Animals; Biomechanical Phenomena; Elastic Tissue; Elastin; Fibroblasts; Humans; Phonation; Vocal Cords; Voice Disorders; Voice Quality

Vocal fold scarring is the greatest cause of poor voice after vocal fold injury. Scarring causes a disruption of the viscoelastic layered structure of the lamina propria, an increase in stiffness of the vibratory structure, and glottic incompetence. Current treatments for this complex condition are inconsistent and often produce suboptimal results. Research investigating this condition has dramatically increased over the last several years. The literature has been directed toward understanding vocal fold scarring at the biological level and translating this to the clinical forum. We present an up-to-date, thorough, and scholarly review of the literature in vocal fold scarring since 1996.

Topics: Adjuvants, Immunologic; Animals; Cicatrix; Collagen; Elastin; Extracellular Matrix Proteins; Growth Substances; Humans; Hyaluronic Acid; Treatment Outcome; Vocal Cords; Voice Disorders; Voice Quality; Wound Healing

Personalized, preemptive, and predictive medicine is a central goal of contemporary medical care. The central aim of the present study was to investigate the utility of mechanistic computational modeling of inflammation and healing to address personalized therapy for patients with acute phonotrauma.. Computer simulation.. Previously reported agent-based models (ABMs) of acute phonotrauma were extended with additional inflammatory mediators as well as extracellular matrix components. The models were calibrated with empirical data for a panel of biomarkers--interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α and matrix metalloproteinase-8--from individual subjects following experimentally induced phonotrauma and a randomly assigned voice treatment namely voice rest, resonant voice exercise, and spontaneous speech. The models' prediction accuracy for biomarker levels was tested for a 24-hour follow-up time point.. The extended ABMs reproduced and predicted trajectories of biomarkers seen in experimental data. The simulation results also agreed qualitatively with various known aspects of inflammation and healing. Model prediction accuracy was generally better following individual-based calibration as compared to population-based calibration. Simulation results also suggested that the special form of vocal fold oscillation in resonant voice may accelerate acute vocal fold healing.. The calibration of inflammation/healing ABMs with subject-specific data appears to optimize the models' prediction accuracy for individual subjects. This translational application of biosimulation might be used to predict individual healing trajectories, the potential effects of different treatment options, and most importantly, provide new understanding of health and healing in the larynx and possibly in other organs and tissues as well.

Topics: Adult; Biomarkers; Blood Platelets; Computer Simulation; Elastin; Extracellular Matrix; Female; Fibroblast Growth Factor 2; Fibroblasts; Humans; Hyaluronic Acid; Inflammation Mediators; Interleukins; Laryngitis; Macrophages; Male; Matrix Metalloproteinase 8; Middle Aged; Phonation; Rest; Sound Spectrography; Speech; Vocal Cords; Voice Disorders; Voice Training; Wound Healing; Young Adult

The voice of persons with Williams syndrome (WS) is described as hoarse with a deep and unstable fundamental frequency (f0). These observations may be justified by the deficit of elastin due to a haplo-insufficiency in the ELN gene characteristic of the syndrome. In view of the possible relationship between elastin deficit and dysphonia, a study of the dynamic function of WS phonation was conducted by means of biomechanical analysis. In order to assess the presence of dysphonic symptoms and their degree of severity, the biomechanical description of WS phonation has been evaluated in terms of dynamic mass and viscoelasticity estimates. Glottal biomechanical features such as vocal fold dynamic mass, stiffness, unbalances, and laryngeal tremor of 12 children with WS aged 3 to 8 years (five girls and seven boys) have been estimated and compared with the normative phonation of 97 children with typical development (53 girls and 44 boys). The results show that WS children show differences in f0, vocal fold mass and stiffness, phonation stability, glottal contact defects, and laryngeal tremor. The conclusions may help to make a more complete view of the connection between WS and dysphonia based on objective assessments.

Topics: Acoustics; Age Factors; Biomechanical Phenomena; Case-Control Studies; Child; Child, Preschool; Chromosome Deletion; Elastin; Female; Humans; Larynx; Male; Phonation; Speech Production Measurement; Voice Disorders; Voice Quality; Williams Syndrome

The human elastin gene (ELN) is responsible for the generation of elastic fibres in the extracellular matrix of connective tissue throughout the body, including the vocal folds. Individuals with Supravalvular aortic stenosis (SVAS) and Williams syndrome (WS) lack one normal ELN allele due to heterozygous ELN abnormalities, resulting in a haploinsufficiency. We measured perceptual and acoustic characteristics of voice quality in individuals with SVAS and WS to investigate the consequences to vocal function secondary to ELN haploinsufficiency. Results indicated that the voice quality of individuals with SVAS/WS was rated as significantly more abnormal, rough, and hoarse compared to normal controls, and that adults with SVAS/WS were rated as significantly lower in pitch. Acoustic measures indicated that individuals with SVAS/WS produced greater instability of fundamental frequency during phonation (as reflected via increased pitch sigma and increased jitter). These findings support the possibility that heterozygous ELN abnormalities negatively influence vocal fold biomechanics and the resulting sound produced by the vibrating glottis.

Topics: Adolescent; Adult; Aortic Stenosis, Supravalvular; Elastin; Female; Genetic Carrier Screening; Haplotypes; Humans; Male; Phenotype; Sound Spectrography; Speech Acoustics; Voice Disorders; Voice Quality; Williams Syndrome

We report on a short-term clinical study of injectable autologous collagen (Vocalogen) used to correct dysphonias arising from vocal fold immobility. The collagen is extracted from skin taken from the lower abdominal quadrant area or from just above the bikini line. About 30 cm2 of skin are required to provide 2 mL of injectable collagen. The histologic examination of the preparation before injection disclosed the presence of elastin fibers and some clusters of epithelial cells, beside the collagen fibers. The collagen is naturally reticulated, and the molecule is preserved in its entirety. The technique is exactly the same as that reported for bovine collagen: injection into Reinke's space, under general anesthesia, monitored by direct microlaryngoscopy. The amount injected is also similar: 1.5 mL for correction of glottic insufficiency in which the immobile vocal fold is in the intermediate position. Eight patients were injected, and the average follow-up was 4.5 months. Voice assessments made before and after the treatment included stroboscopy, subjective and perceptual judgments, and aerodynamic and acoustic measurements. The functional results were similar to those obtained with bovine collagen. No complications arose. The probability of any hypersensitivity reaction, always a possibility to be feared with bovine collagen, is negligible with the autologous collagen. Long-term results are as yet unknown, but from the fact that the collagen molecular structure is intact and there is little risk of foreign body response, it would be expected that autologous preparations would be more stable than bovine collagen; this appears to be the case in cosmetic applications. Autologous collagen could be employed for the same indications as bovine collagen, provided that a delay of 45 days (the time required to prepare the injectable collagen) is acceptable. The amount of collagen required is also a limiting factor, since the patient's own skin is the starting donor material.

Topics: Aged; Collagen; Elastin; Female; Humans; Injections; Male; Middle Aged; Speech Therapy; Treatment Outcome; Vocal Cord Paralysis; Voice Disorders