A Rare Laryngeal Presentation of Stevens-Johnson Syndrome.

Stevens-Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 131:2519-2522, 2021.

Mainstream Cigarette Smoke Impacts the Mouse Vocal Fold Epithelium and Mucus Barrier.

OBJECTIVES/HYPOTHESIS: Cigarette smoke (CS) is a primary risk factor for the development of numerous benign and malignant laryngeal diseases. The epithelium and mucus lining the vocal folds (VF) are the first barriers against CS. The primary objective of this study was to investigate epithelial and mucus barrier changes in the mouse laryngeal mucosa upon exposure to subacute CS. The secondary objective was to compare mucus barrier changes in mice and human smokers and nonsmokers. Study Design Animal model. METHODS: Mice were exposed to CS for 4 weeks for 4 hours (N = 12, high dose [HD]) or 1 hour (N = 12, low dose [LD]) per day. Air-exposed mice were used as a control group (N = 10). Larynges were harvested and VF epithelial barrier integrity was evaluated including cellular proliferation and expression of cell junctions. We also investigated mucus production by examining mucus cell area and mucin expression in mice and human smokers and nonsmokers. RESULTS: HD CS increased VF epithelial cellular proliferation but did not alter the expression of cell junctions. HD CS also induced hypertrophy of the mucus-producing submucosal glands. However, only LD CS increased MUC5AC gene expression. MUC5AC staining appeared elevated in laryngeal specimens from smokers, but this was not significant as compared to nonsmokers. CONCLUSIONS: These findings help us identify potential adaptive mechanisms to CS exposure as well as set the foundation for further study of key aspects of epithelial and mucus barrier integrity that may be implicated in laryngeal disease development following prolonged smoking. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2530-2539, 2021.

Non-Reflex Defense Mechanisms of Upper Airway Mucosa: Possible Clinical Application.

The sinonasal mucosa has an essential role in defense mechanisms of the upper respiratory tract. The innate immune system presents the primary defense against noxious microorganisms followed by induction of the adaptive immune mechanisms as a consequence of the presence of pathogens. This well-known activation of adaptive immune system in response to presence of the antigen on mucosal surfaces is now broadly applicated in vaccinology research. Prevention of infectious diseases belongs to substantial challenges in maintaining the population health. Non-invasive, easily applicable mucosal vaccination purposes various research opportunities that could be usable in daily practice. However, the existence of multiple limitations such as rapid clearance of vaccine from nasal mucosa by means of mucociliary transport represents a great challenge in development of safe and efficient vaccines. Here we give an updated view on nasal functions with focus on nasal mucosal immunity and its potential application in vaccination in nearly future.

Laryngeal Mucosa Alterations in Mice Model of Gastroesophageal Reflux: Effects of Topical Protection.

OBJECTIVES/HYPOTHESIS: The objectives of this study were to evaluate laryngeal inflammation and mucosal integrity in a murine model of reflux disease and to assess the protective effects of topical agents including alginate, hyaluronic acid, and cashew gum. STUDY DESIGN: Animal study. METHODS: A surgical murine model of reflux disease was evaluated at 3 or 7 days postsurgery, and laryngeal samples were collected to measure inflammation (wet weight and myeloperoxidase [MPO]) and mucosal integrity (transepithelial resistance [TER] and mucosal permeability to fluorescein). Additional groups of animals were administered one of several topical agents (alginate, hyaluronic acid, or cashew gum) daily, and laryngeal inflammation and mucosal integrity were evaluated at 3 days postsurgery. RESULTS: At 3 days, and not 7 days postsurgery, we observed increased laryngeal wet weight and MPO, decreased laryngeal TER, and increased laryngeal mucosa permeability. Alginate partially decreased laryngeal inflammation (wet weight and not MPO) and dramatically improved laryngeal mucosal integrity. Conversely, hyaluronic acid eliminated the inflammation; however, it had no effect on laryngeal mucosal integrity impairment. Cashew gum eliminated laryngeal inflammation as well as the impairment in laryngeal mucosal integrity. CONCLUSIONS: This study shows that a surgical model of reflux disease induced laryngeal inflammation and impairment in laryngeal barrier function. These observed alterations were partially attenuated by alginate and hyaluronic acid and completely reversed by cashew gum. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.

Topical protection of mice laryngeal mucosa using the natural product cashew gum.

OBJECTIVES/HYPOTHESIS: Evaluate the effect of in vitro exposure of mice laryngeal mucosa to solutions that simulated human gastric juice and to assess the topical protective effect of cashew gum on mice laryngeal mucosal integrity in vitro. STUDY DESIGN: Animal study. METHODS: Murine (Swiss) laryngeal samples were mounted in Ussing chambers. The luminal side of biopsies was exposed to solutions of different acidity with or without pepsin and/or taurodeoxycholic acid (TDC). Transepithelial electrical resistance (TER) was continuously recorded. The topical protective effect of cashew gum solution was evaluated by precoating the biopsies before the exposure with a solution at pH 5 containing 5 mM TDC. Changes in TER and mucosal permeability to fluorescein were measured. RESULTS: Exposure of laryngeal mucosa to acidic solutions containing pepsin and TDC provoked a pH-dependent drop in TER with the maximal effect at pH 1, but still present at pH 5 (weakly acidic). The exposure of the laryngeal mucosa to a solution of pH 5 with TDC, but not with pepsin, produced a dose-dependent decrease in TER. Precoating the mucosa with cashew gum prevented the reduction of TER and increased transepithelial permeability by exposure to a solution at pH5 containing TDC. CONCLUSIONS: Weakly acidic solutions containing bile acids can produce impairment of laryngeal epithelial barrier, which may be protected by topical treatment with cashew gum. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1157-1162, 2018.

The Effects of Passive Smoking on Laryngeal and Tracheal Mucosa in Male Wistar Rats During Growth: An Experimental Study.

Cigarettes contain toxic and carcinogenic substances. In this context, cigarette smoking, and similar activities, are associated with numerous pathologies, being considered a risk factor in up to 10% of the total number of deaths in adults. Recent evidence suggests that the exposure of children to smoking in the early days of their development causes many diseases. Using light microscopy, this study aims to analyze the possible histopathological effects of an experimental model of chronic inhalation of cigarette smoke (passive smoking) on the laryngeal and tracheal mucosa of young Wistar rats. A total of 24 young Wistar rats were studied for a period of 120 days. The animals were divided into two groups: passive smoking (n = 16) and control (n = 8). The level of exposure to cigarette smoke was evaluated from the urinary cotinine level. Although no cancerous lesions were identified, histopathological analysis in the laryngeal and tracheal mucosa of all the animals in the experimental group showed that the proportion of moderate and focal inflammation was higher in animals exposed to chronic inhalation of cigarette smoke (P = 0.041). Histopathologic analysis revealed moderate and focal inflammatory lesions in the region of the infraglottic mucosa in exposed animals, although without dysplastic or neoplastic lesions in the laryngeal and tracheal mucosa.

Laryngeal mucus hypersecretion is exacerbated after smoking cessation and ameliorated by glucocorticoid administration.

INTRODUCTION: The mechanisms underlying the effects of cigarette smoke and smoking cessation on respiratory secretion, especially in the larynx, remain unclear. OBJECTIVES: The aims of this study were to determine the effects of cigarette smoke and smoking cessation on laryngeal mucus secretion and inflammation, and to investigate the effects of glucocorticoid administration. METHODS: We administered cigarette smoke solution (CSS) to eight-week-old male Sprague Dawley rats for four weeks, then examined laryngeal mucus secretion and inflammatory cytokine expression on days 1, 28 and 90 after smoking cessation. We also investigated the effects of the glucocorticoid triamcinolone acetonide when administered on day 1 after smoking cessation. RESULTS: Exposure to CSS resulted in an increase in laryngeal mucus secretion that was further excacerbated following smoking cessation. This change coincided with an increase in the expression of mRNA for the inflammatory cytokines tumor necrosis factor and interleukin-6, as well as mRNA for MUC5AC, which is involved in mucin production. Triamcinolone suppressed CSS-induced laryngeal mucus hypersecretion and pro-inflammatory cytokine production. CONCLUSION: Cigarette smoke-associated inflammation may contribute to the exacerbated laryngeal mucus hypersecretion that occurs following smoking cessation. The inflammatory response represents a promising target for the treatment of cigarette smoke-associated mucus hypersecretion.

Evaluation of the antioxidant effects of melatonin on the larynx mucosa of rats exposed to environmental tobacco smoke.

OBJECTIVES: This study's aim was to investigate the effect of melatonin in terms of mitigating the effects of smoking on the laryngeal mucosa of rats exposed to environmental tobacco smoke. DESIGN: Rats were divided into four groups: Melatonin + Smoking group exposed to smoke with melatonin; Smoking group exposed to smoke without melatonin; Saline group not exposed to smoke without melatonin; Melatonin group not exposed to smoke with melatonin. CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in plasma and tissues. Tissues were also examined the changes of squamous hyperplasia, keratosis, parakeratosis and epithelial hyperplasia by light microscope and the ultrastructural changes by electron microscope. RESULTS: Tissue SOD, CAT and GSH-Px activities were significantly higher in Saline and Melatonin groups than Melatonin + Smoking and Smoking groups. Plasma CuZn-SOD and CAT activities were significantly higher in Saline and Melatonin groups than Smoking group. Plasma GSH-Px showed no significant difference. The rate of epithelial hyperplasia was significantly higher in Smoking group than the other groups. The rate of parakeratosis was significantly higher in Smoking group than the other groups. The epithelial cells in Melatonin + Smoking group displayed, normal cell structure similar to those in Saline group under electron microscope. CONCLUSIONS: The study shows that smoking induces substantial pathological changes in the laryngeal mucosa and melatonin may have some beneficial effects in partially reversing smoking-induced laryngeal injury by inducing the expression of antioxidants; biochemical and histological outcomes also support these findings due to preventing tissue damage in laryngeal mucosa exposed to smoke.

Epidermal growth factor mediated healing in stem cell-derived vocal fold mucosa.

BACKGROUND: The goal of vocal fold wound healing is the reconstitution of functional tissue, including a structurally and functionally intact epithelium. Mechanisms underlying reepithelialization in vocal folds are not known, although it is suspected that healing involves the interplay between several growth factors. We used a three-dimensional human embryonic stem cell-derived model of vocal fold mucosa to examine the effects of one growth factor, exogenous epidermal growth factor (EGF), on wound healing. MATERIALS AND METHODS: A scratch wound was created in the in vitro model. Rate of wound healing, epidermal growth factor receptor (EGFR) activation, and cell proliferation after injury were analyzed with and without application of both exogenous EGF and an EGFR inhibitor, gefitinib. RESULTS: Wound repair after injury was significantly hastened by application of exogenous EGF (13.3 µm/h, ± 2.63) compared with absence of exogenous EGF (7.1 µm/h ± 2.84), but inhibited with concurrent addition of Gefitinib (5.2 µm/h, ± 2.23), indicating that EGF mediates wound healing in an EGFR-dependent manner. Immunohistochemistry revealed that EGFR activation occurred only in the presence of exogenous EGF. Although not statistically significant, increased density of Ki67 staining in the epithelium adjacent to the scratch wound was observed after treatment with EGF, suggesting a tendency for exogenous EGF to increase epithelial cell proliferation. CONCLUSIONS: Exogenous EGF increases the rate of wound healing in an EGFR-dependent manner in a three-dimensional stem cell-derived model of vocal fold mucosa. This model of wound healing can be used to gain insight into the mechanisms that regulate vocal fold epithelial repair after injury.

Potential of biofluid components to modify silver nanoparticle toxicity.

Establishing realistic exposure scenarios is critical for cytotoxic investigation of silver nanoparticles (AgNP) in the gastrointestinal tract. This study investigated the potential interaction with and effect of biofluid components, namely cholic acid, deoxycholic acid and ursodeoxycholic acid, on AgNP toxicity. Two cell lines corresponding to organs related to the biofluid components were employed. These were HepG-2 a hepatocellular carcinoma derived from liver tissue and Hep2 an epithelial cell line. Physiochemical and cytotoxic screening was performed and the ability of biofluid components to modify AgNP cytotoxicity was explored. No alteration to the physiochemical characteristics of AgNP by biofluid components was demonstrated. However, biofluid component addition resulted in alteration of AgNP toxicity. Greater reactive oxygen species induction was noted in the presence of cholic acid and deoxycholic acid. Ursodeoxycholic acid demonstrated no modification of toxicity in HepG-2 cells; however, significant modification was noted in Hep2 cells. It is concluded that biofluid components can modify AgNP toxicity but this is dependent on the biofluid component itself and the location where it acts.

Effects of Electronic Nicotine Delivery System on Larynx: Experimental Study.

OBJECTIVE: We aimed to assess the effects of electronic nicotine delivery system (ENDS) or also termed electronic cigarette vapor on the laryngeal mucosa of rats. MATERIALS AND METHODS: Sixteen female Wistar albino rats were divided into two groups. The study group was exposed to ENDS vapor for 1 hour/day for 4 weeks. The control group was not subjected to any chemical or physical stimulus. The vocal folds of the study and control group rats were evaluated histopathologically by hematoxylin and eosin staining and immunohistochemically by Ki67 staining. Epithelial distribution, inflammation, hyperplasia, and metaplasia were evaluated. RESULTS: Epithelial distribution and inflammation did not differ between the two groups. Two cases of hyperplasia were detected in the study group but there was no hyperplasia in the control group. Four cases of metaplasia were detected in the study group and one case in the control group. Statistical analysis revealed no significant difference between the study and control groups (P = 0.131 and 0.106, respectively). CONCLUSIONS: Exposure to ENDS for 4 weeks caused hyperplasia and metaplasia of the laryngeal mucosa of rats but this was not significant statistically. These results implemented that further studies with larger cohort and longer duration are required to evaluate long-term effects.

Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells.

Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration-dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration-dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real-time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up-regulated whereas the anti-apoptotic gene bcl-2 was down-regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase-3 and caspase-9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N-acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level.

Bicarbonate availability for vocal fold epithelial defense to acidic challenge.

OBJECTIVES: Bicarbonate is critical for acid-base tissue homeostasis. In this study we investigated the role of bicarbonate ion transport in vocal fold epithelial defense to acid challenges. Acidic insults to the larynx are common in gastric reflux, carcinogenesis and metastasis, and acute inflammation. METHODS: Ion transport was measured in viable porcine vocal fold epithelium. First, 18 vocal folds were exposed to either the carbonic anhydrase antagonist acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a control buffer or a bicarbonate-free buffer on their luminal or basolateral surface or both. Third, 32 vocal folds were challenged with acid in the presence of bicarbonate-free or control buffer. RESULTS: The vocal fold transepithelial resistance was greater than 300 Ω*cm(2), suggesting robust barrier integrity. Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure to bicarbonate-free buffer did not compromise vocal fold ion transport (p > 0.05). Ion transport increased after acid challenge. This increase approached statistical significance and was the greatest for the control buffer and for the bicarbonate-free buffer applied to the basolateral surface. CONCLUSIONS: Bicarbonate secretion may contribute to vocal fold defense against acid challenge. Our data offer a potential novel role for bicarbonate as a therapeutic agent to reduce pH abnormalities in the larynx and prevent associated pathological changes.

Histological effects of inhaled corticosteroids and ß2-agonists on laryngeal mucosa in an allergic rat model.

OBJECTIVE: To constitute an animal model of laryngeal allergy and evaluate the laryngeal effects of inhaled corticosteroids and ß2-agonists on the laryngeal mucosa in an allergic rat model. STUDY DESIGN: Prospective randomized. SETTING: The Experimental Medical Research Institute (DETAE) at Istanbul University. SUBJECTS AND METHODS: Wistar Albino rats (n = 32) were sensitized with ovalbumin. Unsensitized rats (n = 8) served as controls. The rats were exposed to aerosolized ovalbumin (1%). On days 28 through 42, every 2 days preceeding ovalbumin exposure, rats were further exposed to aerosolized phosphate buffered saline (n = 8), fluticasone propionate (n = 8), salbutamol (n = 8), and combined salbutamol+fluticasone propionate (n = 8). Inflammatory cell infiltration was graded semi-quantitatively. The quantitative data included mast cell count and degranulation. Ultrathin sections were investigated under transmission electron microscope. RESULTS: The simultaneous and pairwise comparison of groups (Kruskal-Wallis) revealed statistically significant difference among groups at supraglottic level (critical P < .05, <.01) and no difference at glottic level. In ovalbumin+phosphate buffered saline exposed rats, the light microscopy of supraglottic mucosa revealed regular epithelium with severe inflammatory cell infiltration and increased mast cell count. Electron microscopy revealed increased mast cell degranulation. Increased inflammatory cell infiltration was detected along with reduced mast cell count among fluticasone propionate treated rats. Mild inflammatory cell infiltration was encountered in combined salbutamol+fluticasone propionate treated rats. CONCLUSION: This study supported the presence of localized allergic reaction in the supraglottic laryngeal mucosa through the observation of increased mast cell number and degranulation. It was also shown that inhaled corticosteroids increase inflammation whereas combined inhaled corticosteroids and ß2-agonists minimize allergic and inflammatory reactions in supraglottic laryngeal mucosa providing a safer therapeutic option.

Does treatment of the laryngeal mucosa reduce dystonic symptoms? A prospective clinical cohort study of mannose binding lectin and other immunological parameters with diagnostic use of phonatory function studies.

This study examined efficacy of the innate immune defence via the mannose binding lectin (MBL) in a cohort of 55 dystonic patients prospectively referred to the clinic with laryngeal mucosal complaints, who were placed on local steroids (budesonid inhaler, 400 µg 2 times daily) and antihistamines (fexofenadin 180 mg mostly 3 times daily) with adjuvant lifestyle corrections. Treatment efficacy of the larynx was assessed based on mucosal findings of the vocal folds examined with phonatory function studies (PhFS) comprising simultaneous high-speed digital images, kymography, electroglottography and voice acoustics combined with a visual score of arytenoids oedema, as these measures are indicative of the magnitude of laryngitis. Lactose and gluten intolerance and immunological analyses of the innate system were made systematically. Results showed that the genetic aspects of immunology did not reveal a role for the innate immune system, represented by the MBL. But an unexpected positive effect of the larynx treatment on dystonia symptoms was found evidenced by reduction of dystonic complaints and more normative results of PhFS, and a reduction of oedema of the inter arytenoids region. Symptoms relieve and better quality of life was observed on follow-up for the dystonia complaints.

Effects of ovariectomy and estrogen replacement therapy on laryngeal tissue: a histopathological experimental animal study.

OBJECTIVE: To determine the histopathological effect of estrogen deficiency and hormone replacement treatment on laryngeal tissue in ovariectomized rats. STUDY DESIGN: Animal study. SETTING: The study was conducted at the animal experiment laboratory of Marmara University School of Medicine, Istanbul, Turkey. SUBJECTS AND METHODS: Six-month-old female Wistar albino rats were divided into the following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and ovariectomized with estrogen replacement. Rats in the ovariectomized with estrogen replacement group received 17 ß-estradiol valerate (200 µg/kg, subcutaneously) once a week. Animals were killed after 8 weeks of intervention. RESULTS: Significant changes were observed in the ovariectomized group when edema in lamina propria, inflammation in squamous, respiratory epithelia and lamina propria, pseudostratification, and cilia loss were assessed. Except cilia loss, there were no significant differences in the assessments between the sham-operated control and ovariectomized with estrogen replacement groups. CONCLUSIONS: On the basis of histopathological evaluations, it was shown that estrogen replacement helped to improve laryngeal changes due to experimentally induced menopause.

Acute stress to excised vocal fold epithelium from reactive oxygen species.

OBJECTIVES/HYPOTHESIS: Vocal fold epithelium is exposed to reactive oxygen species from the inhaled environment and from tissue inflammation. The objective of this study was to explore the functional and structural consequences of reactive oxygen species exposure on vocal fold epithelium. STUDY DESIGN: In vitro, prospective study design. METHODS: Hydrogen peroxide (H(2)O(2)), a common reactive oxygen species, was utilized in this study. Freshly excised, viable porcine vocal fold epithelia (N = 32) were exposed to H(2) O(2) or sham challenge for 2 hours. Electrophysiology, western blotting, and light microscopy were used to quantify the functional and structural effects of reactive oxygen species on vocal fold epithelia. RESULTS: Exposure to reactive oxygen species did not significantly alter transepithelial resistance. There was a small, nonsignificant trend for decreased concentration of epithelial junctional complex protein with reactive oxygen species challenge. Minimal changes to the gross structural appearance of vocal fold epithelia were also noted. CONCLUSIONS: The stratified squamous epithelia of the vocal folds effectively defend against an acute reactive oxygen species challenge. The current study lays the groundwork for future investigations on the effects of reactive oxygen species on vocal fold epithelia that are compromised from phonotrauma.

Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

OBJECTIVES: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. METHODS: We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. RESULTS: High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. CONCLUSIONS: The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

In Vivo engineering of the vocal fold ECM with injectable HA hydrogels-late effects on tissue repair and biomechanics in a rabbit model.

OBJECTIVES: To determine if the utilization of injectable chemically modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix (ECM) and lamina propria 6 months after treatment. STUDY DESIGN: Prospective, controlled animal study. METHODS: Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed 6 months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, transforming growth factor beta one (TGF-ß1), HA synthase, and hyaluronidase, and tissue biomechanics-viscosity and elasticity. RESULTS: Extracel-treated vocal folds were found to have significantly less fibrosis than saline-treated controls. Extracel-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-ß1, procollagen I, and HA synthase were measured. CONCLUSIONS: Prophylactic in vivo manipulation of the ECM with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months.

Characterization of vocal fold scar formation, prophylaxis, and treatment using animal models.

PURPOSE OF REVIEW: To review recent literature on animal models used to study the pathogenesis, detection, prevention, and treatment of vocal fold scarring. Animal work is critical to studying vocal fold scarring because it is the only way to conduct systematic research on the biomechanical properties of the layered structure of the vocal fold lamina propria, and therefore develop reliable prevention and treatment strategies for this complex clinical problem. RECENT FINDINGS: During the period of review, critical anatomic, physiologic, and wound healing characteristics, which may serve as the bases for selection of a certain species to help answer a specific question, have been described in mouse, rat, rabbit, ferret, and canine models. A number of different strategies for prophylaxis and chronic scar treatment in animals show promise for clinical application. The pathways of scar formation and methods for quantifying treatment-induced change have become better defined. SUMMARY: Recent animal vocal fold scarring studies have enriched and confirmed earlier work indicating that restoring pliability to the scarred vocal fold mucosa is challenging but achievable. Differences between animal models and differences in outcome measurements across studies necessitate considering each study individually to obtain guidance for future research. With increased standardization of measurement techniques it may be possible to make more inter-study comparisons.