The life-cycle and restoration of the human vocal fold

Abstract

Objective: To better understand the challenges of designing therapies to treat damaged vocal fold lamina propria, it is essential to understand the biophysical and pathophysiological mechanisms involved in vocal fold development, maintenance, injury, and aging. This review critically analyses these points to try and direct future efforts and new strategies toward science-based solutions.

Data sources & review methods: MEDLINE, Ovid Embase, and Wed of Science databases were used to identify relevant literature. A scoping review was performed following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews checklist.

Results: The layered arrangement of the vocal fold, develops during early childhood and is maintained during adulthood unless injury occurs. The stellate cells of the macular flava are likely to be important in this process. The capacity for vocal fold regeneration and growth is lost during adulthood and repair results in the deposition of fibrous tissue from resident fibroblasts. With advancing age, viscoelastic tissue declines, possibly due to cell senescence. Strategies aimed at replacing fibrous tissue within the vocal folds must either stimulate resident cells or implant new cells to secrete healthy extracellular protein. Injection of basic fibroblast growth factor is the most widely reported therapy that aims to achieve this.

Conclusions: The pathways involved in vocal fold development, maintenance and aging are incompletely understood. Improved understanding has the potential to identify new treatment targets that could potentially overcome loss of vocal fold vibratory tissue.

Keywords: regenerative medicine; tissue‐engineering; vocal fold biology; vocal fold regeneration.

FIGURE 1

An axial and sagittal diagram of the vocal cords. The relevant structures are identified. DLP, deep lamina propria; ILP, intermediate lamina propria; SLP, superficial lamina propria

FIGURE 2

The life cycle of the vocal fold is presented. Example one demonstrates a normal life cycle whereby there is expansion of viscoelastic tissue in childhood followed by maintenance in adulthood. As the individual ages, the viscoelastic tissue begins to decline. Example two represents an individual with an early onset decline in viscoelastic tissue due to aging in keeping with presbyphonia. Example three demonstrates sustained and repetitive injury due to voice misuse or factors such as tobacco smoke. Example four represents the life cycle of an individual that suffers damage to the lamina propria resulting in fibrosis or tissue loss. There is a rapid decline in available viscoelastic tissue. Providing there is no further injury, viscoelastic tissue is unlikely to change up to the point where age‐related decline occurs. In both example three and four, the effects of aging are likely to have a greater impact on vocal function as there is less viscoelastic tissue to lose at onset.

FIGURE 3

A flowchart presenting the pathways for success or failure of novel therapies that aim to restore vocal fold viscoelasticity. Therapies can be divided into implantable and injectable treatments. Any implanted material eventually undergoes encapsulation or remodeling and resorption. These processes can influence the surrounding cellular microenvironment with deposition of viscoelastic extracellular matrix protein that enables restoration of vibration or, deposition of fibrous tissue that does not.