Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

Abstract

Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice.

A Review of Hyaluronic Acid and Hyaluronic Acid-based Hydrogels for Vocal Fold Tissue Engineering

“…This review is organized into the following sections: vocal fold composition, vocal fold biomechanics, pathophysiology of vocal fold scarring with an emphasis on changes in HA, and current HA-based tissue engineering solutions for scarring. The readers are directed to comprehensive reviews by Fishman et al 16 for recent advances in stem cell-based regeneration, and by Li et al 17 for broader perspectives in vocal fold tissue engineering.…”

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS)

“…Various types of biological materials and biomimetic scaffolds have been proposed as candidates of tissue substitutes for vocal fold reconstruction involving surgical repair of lamina propria deficits, including scarring, fibrosis, tissue loss and atrophy. Such materials have included biologic ECM scaffolds, HA hydrogels, as well as aligned biomimetic scaffolds being identified as promising implants for vocal fold repair [24-27]. A better characterization of their nonlinear viscoelastic properties under LAOS in comparison with those of the vocal fold cover and vocal ligament would allow for optimized functional biomechanical and vibratory performance of the tissue substitutes during phonation.…”

50th Anniversary Perspective: Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry

“…82–84 These encouraging findings have initiated applications of RLP materials in biorubbers, nanosprings, diagnostic biosensors and in regenerative medicine as elastomeric tissue engineering scaffolds. 81, 84–87 Our group has designed constructs combining the resilin consensus motif (GGRPSDSYGAPGGGN) with bioactive domains to impart cell adhesion, proteolytic degradation and heparin immobilization functions in tunable bioelastomers for mechanically demanding applications such as in therapies for vocal folds and cardiovascular tissues. 83, 88–90 Hydrogels with different cell adhesion morphologies and matrix degradation profiles can be produced without compromising desired mechanical features (e.g., oscillatory shear moduli, Young’s moduli, resilience and stress relaxation), 84, 91 offering substantial opportunities for reproducibility, tunable biocomplexity and dynamic multifunctionality (Figure 3).…”