Susan L. Thibeault

Characterization of Vocal Fold Scarring in a Canine Model

Objective The objective was to assess the histological and viscoelastic shear tissue properties of the scarred vocal fold lamina propria at 2 and 6 months postoperatively in a canine model.

Hyaluronic Acid: Its Role in Voice

The extracellular matrix (ECM), once regarded simply as a structural scaffold, is now recognized as an important modulator of cellular behavior and function. One component that plays a prominent role in this process is hyaluronic acid (HA)--a molecule found in many different tissues. Research into the roles of HA indicates that it plays a key role in tissue viscosity, shock absorption, and space filling. Specifically, research into the role of HA in laryngology indicates that it has profound effects on the structure and viscosity of vocal folds. This article provides an introduction to the structure and biological functions of HA and its importance in voice. In addition, an overview of the pharmaceutical applications of HA is discussed.

In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels : Early effects on tissue repair and biomechanics in a rabbit model

Objectives: A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. Methods: We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives — Carbylan-SX and HA-DTPH-PEGDA — at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. Results: The Carbylan-SX—treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX—treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Conclusions: Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.

Hyaluronan levels in acute vocal fold scar

Objectives/Hypothesis The objective was to measure the level of hyaluronan during the first 15 days after vocal fold biopsy in a rabbit model.

Injectable synthetic extracellular matrices for tissue engineering and repair.

The development of novel biointeractive hydrogels for tissue engineering1, 2, 3, tissue repair, and release of drugs4 and growth factors5 has attracted considerable attention over the past decade. Our attention has focused on hydrogels based on the extracellular matrix (ECM), a heterogeneous collection of covalent and noncovalent molecular interactions comprised primary of proteins and glycosaminoglycans (GAGs)6. In the ECM, covalent interactions connect chondroitin sulfate (CS), heparan sulfate (HS) and other sulfated GAGs to core proteins forming proteoglycans (PGs). Noncovalent interactions include binding of link modules of PGs to hyaluronan (HA), electrostatic associations with ions, hydration of the polysaccharide chains, and triple helix formation to generate collagen fibrils.

Fibronectin: an interesting vocal fold protein.

A great deal of information is accruing regarding the function of the extracellular matrix. Once thought to be simply a structural entity to surround cells, it is now known to do much more. Fibronectin in particular has received specific attention. Fibronectin is a ubiquitous glycoprotein found most abundantly in the extracellular matrix of regenerating, healing, and embryonic tissue. Vast evidence supports the fact that fibronectin participates in many diverse functions throughout the body that are relevant to vocal fold biology. This article introduces the structure of fibronectin and its isoforms and provides an introduction to some of the many functions it plays. It also reviews the evidence about fibronectins place in vocal folds and vocal fold pathology. It discusses fibronectins presence in vocal nodules, vocal polyps, vocal scarring, and Reinkes edema, and reviews the data on its role in mucosal wave impairment. Lastly, it discusses preliminary microarray data that show gene expression for fibronectin to be upregulated in true vocal folds when compared to false vocal folds.

Microarray analysis of allergic fungal sinusitis and eosinophilic mucin rhinosinusitis

OBJECTIVE: Our goal was to determine and compare the differential gene expression in allergic fungal sinusitis (AFS) and eosinophilic mucin rhinosinusitis (EMRS). STUDY DESIGN AND SETTING: We conducted a complementary DNA microarray analysis of prospectively gathered tissue from a tertiary rhinology practice. RESULTS: Compared to normal subjects, 38 genes or potential genes were differentially expressed in AFS patients, while 10 genes were differentially expressed in EMRS patients. Four genes differentially expressed in EMRS were not differentially expressed in AFS: cathepsin B, sialyltransferase 1, GM2 ganglioside activator protein, and S100 calcium binding protein. These genes mediate lysosomal activity and are known to have differential expression in inflammatory and neoplastic states. CONCLUSIONS: EMRS and AFS show some similarities in gene expression profiles using microarray analysis. Significant differences in gene expression in both EMRS and AFS patients compared with normal subjects provide early clues to the pathophysiology of EMRS and AFS. SIGNIFICANCE: This study demonstrates that complementary DNA microarray analysis is a feasible tool for studying different disease subclassifications and is the first to study these subclasses in chronic rhinosinusitis.

Time and dose effects of mitomycin C on extracellular matrix fibroblasts and proteins.

Objectives/Hypothesis: The objective was to determine treatment dose and time‐dependent effects of injected mitomycin C on extracellular matrix fibroblasts, collagen, and fibronectin, important mediators in the wound healing response, in a rat cutaneous wound model.

Diversity in voice characteristics--interaction between genes and environment, use of microarray analysis.

UNLABELLED Genetic information is used by the cells to make proteins. These proteins are then used to perform cellular and tissue functions. This process is briefly reviewed. Research to identify genes and their expression patterns is a fruitful field in the area of voice disorders. Gene expression studies of vocal lesions illustrates why this type of research is important. The role of microarray analysis (MA) to find genes of interest is discussed. Gene expression may be influenced by various environmental factors. This interaction between environment and genes is constantly manifested in many vocal characteristics and disorders. Since the end result of the gene-environment interaction is the production of cellular and tissue proteins, the field of proteomics is relevant to voice disorders. Some voice disorders have been treated successfully through using proteomic approaches. LEARNING OUTCOMES (a) Understand the factors that influence genetic expression; (b) display a knowledge of why the study of proteins is important to understand voice characteristics; (c) become familiar with MA, a powerful tool for the study of gene expression; and (d) describe the interaction between genes and environment.

Witnessing a revolution in voice research: genomics, tissue engineering, biochips and what's next!

Due to advances in genomics and tissue engineering, new tools and methods are available for use in voice research. Microarray analysis, a method for examining the expression levels of thousand of genes within 24–48 hours, is a very powerful research tool and has greatly hastened the development of biochips for medical application. The use of microarray analysis in voice research will be discussed and the feasibility of a biochip for voice is presented. Gene expression profiles, a fundamental part of biochip development, are now commonly performed in some voice laboratories. Tissue engineering initiatives have led to the ability to grow and work with laryngeal fibroblasts. Because of the extreme conditions (intense vibration, exposure to inhalants, etc.) that vocal fold fibroblasts tolerate, engineering living lamina propria of vocal folds is complex and challenging. Research efforts to explore these conditions in-vitro and their effect on fibroblast growth is detailed. In summary, applying tools from genomic and tissue engineering fields to vocal science is fruitful and holds great clinical promise.