Summary Vocal fold scarring is a common cause of dysphonia. Current treatments involving vocal fold augmentation do not yield satisfactory outcomes in the long term. Tissue engineering and regenerative medicine offer an attractive treatment option for vocal fold scarring, with the aim to restore the native extracellular matrix microenvironment and biomechanical properties of the vocal folds by inhibiting progression of scarring and thus leading to restoration of normal vocal function. Hyaluronic acid is a bioactive glycosaminoglycan responsible for maintaining optimum viscoelastic properties of the vocal folds and hence is widely targeted in tissue engineering applications. This review covers advances in hyaluronic acid-based vocal fold tissue engineering and regeneration strategies.

Here we present an injectable PEG/collagen hydrogel system with robust networks for use as elastomeric tissue scaffolds. Covalently crosslinked PEG and physically crosslinked collagen form semi-interpenetrating networks. The mechanical strength of the hydrogels depends predominantely on the PEG concentration but the incorporation of collagen into the PEG network enhances hydrogel viscoelasticity, elongation, and also cell adhesion properties. Experimental data show that this hydrogel system exhibits tunable mechanical properties that can be further developed. The hydrogels allow cell adhesion and proliferation in vitro. The results support the prospect of a robust and semi-interpenetrating biomaterial for elastomeric tissue scaffolds applications.

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Optimal hydration is thought to be necessary for maintaining healthy vocal folds. Whether in vivo systemic dehydration induces vocal fold dehydration is not fully understood. Furthermore, whether systemic rehydration of vocal folds following systemic dehydration has not been investigated. Due to the ubiquitous nature of water in the body, the complex physiological mechanisms in place to maintain body hydration, and the often insensitive markers of hydration status, we set out to design an animal model to study how systemic dehydration affects the vocal folds. The objectives of this study include (1) identifying the optimal animal model for investigations of systemic dehydration and systemic rehydration, (2) developing a reliable and physiologically relevant methodology of systemic dehydration, (3) developing markers of systemic dehydration and (4) demonstrating whether systemic dehydration induces vocal fold dehydration through a combination of methodologies. Sprague Dawley (SD) rats (males and females) and New Zealand White rabbits (males) were used for systemic dehydration and rehydration studies. Rats were systemically dehydrated to an average of 10% reduction in body weight by withholding water. Rabbits were given 5 mg/kg furosemide IP to induce a moderate level of systemic dehydration based on 5% body weight loss. Body weight loss due to dehydration was corroborated by parameters of hemoconcentration. Proton‐density weight MRI at variable dehydration states, genomic analysis of vocal folds, and histopathology were all investigated to determine effects of systemic dehydration. Proton‐density weighted MR imaging can be used to demonstrate that systemic dehydration reliably induces vocal fold dehydration as detected by signal intensity changes. These changes however, are only detected at high body weight loss levels (> 6% body weight loss). Acute episodes of systemic dehydration do not produce reliable, adverse pathological changes to the vocal folds as assessed by histopathology and gene expression studies. Access to water does not induce rehydration if defined by body weight. There are challenges in inducing physiologically‐relevant systemic dehydration and developing a robust and reliable animal model to study the pathobiology of vocal fold dehydration. A combination of techniques are necessary to confirm that dehydration, in an otherwise healthy animal, is occurring; and that dehydration of the body is dehydrating the vocal folds. The sequelae of chronic versus acute dehydration, and systemic dehydration versus surface dehydration also need to be parsed out. Support or Funding Information NIH R01DC015545