Regeneration of Aged Vocal Fold: First Human Case Treated With Fibroblast Growth Factor

Background/Objectives: Aged vocal folds are characterized by atrophy of the mucosa, which causes dysphonia and is difficult to treat. We have revealed a therapeutic potential of basic fibroblast growth factor (bFGF) for tissue regeneration of the aged vocal fold. We report here the first human case that has been treated with bFGF. Study Design: Institutional review board approved clinical human trial. Methods: A 63‐year‐old man with atrophied vocal folds was treated by local injection of 10 μg of bFGF into the left vocal fold under topical anesthesia. The effects of the injection were examined after 1 to 3 months by videostroboscopy, acoustic and aerodynamic measurements. Results: The atrophy of the vocal fold was improved at 1 week after the injection and glottic gap disappeared. Aerodynamic and acoustic parameters also showed remarkable improvement. These positive effects were maintained up to 3 months. Conclusion: The first case with aged vocal folds treated with bFGF administration is presented. The results are encouraging, suggesting therapeutic effects of bFGF for atrophied vocal folds in human.     

Adipose tissue formation in response to basic fibroblast growth factor

CONCLUSION: Formation of new fat cells may occur in injected adipose tissue in response to basic fibroblast growth factor (bFGF). OBJECTIVE: In an effort to prevent loss of fat volume and generation of additional adipose tissue after intracordal injection of autologous fat, the effects of injecting fat together with basic fibroblast growth factor bFGF were evaluated. MATERIALS AND METHODS: Models of bilateral recurrent laryngeal nerve paralysis were prepared using 12 beagle dogs. Autologous fat was injected into one vocal cord, and a mixture of autologous fat with bFGF, gelatin microspheres, and collagen sponge was injected into the other. Histologic reactions were examined over time. RESULTS: In vocal cords where autologous fat was injected together with bFGF, fusiform immature adipocytes were found in the injected fat at 8 weeks after injection. The volume of the injected fat was maintained almost completely even at 24 weeks after injection. Vocal cords where only autologous fat was injected showed a marked decrease in volume of injected fat over time.     

Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model

ObjectivesVocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring.MethodsSprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed.ResultsA significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction.ConclusionSignificant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring.     

Long-term outcomes of basic fibroblast growth factor treatments in patients with vocal fold scarring,aged vocal fold,and sulcus vocalis

ObjectiveFibrotic changes in the vocal fold mucosa have been observed in patients with vocal fold scarring, aged vocal fold, and sulcus vocalis, which often lead to severe voice disorders. Previous research suggests that the basic fibroblast growth factor (b FGF) improves variations in vocal fold properties [1,2]. Although clinical studies on b FGF treatments have been conducted [3,4,5], these studies only demonstrated the efficacy of this drug over a short period. The present study is the first to investigate the long-term efficacy of b FGF treatment.Methodsb FGF injections were performed in six patients from January of 2016 to December of 2017 at our institution. Patient follow-up continued for at least two years after the last injection. Three patients had vocal fold scarring, two had aged vocal fold atrophy, and one patient had sulcus vocalis. Each vocal fold was injected with 10 µg of b FGF four times. Voice and stroboscopic examinations were performed after surgery (at one month, three months, six months, one year, two years). Fundamental frequency, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), pitch perturbation quotient (PPQ), and noise-to-harmonic ratio (NHR), and voice handicap index-10 (VHI-10) were examined and compared statistically between the pretreatment time and at each posttreatment time point.ResultsThe speaking F0 had an obvious decreasing tendency, with significant differences suggesting the increase in volume in the vocal folds. Aerodynamic parameters also showed small improvements. The most remarkable improvement was observed in the acoustic parameters, indicating that the treatment could improve the vocal fold to make vibrations symmetrically and regularly for a long period. Achievement of symmetry and regularity on vocal fold vibrations suggested the property changes had happened in the vocal folds. Consequently, the score of VHI-10 had improved, indicating high patient satisfaction with this treatment.Conclusionb FGF injections could be a reliable treatment option for diseases that deteriorate the property of vocal fold.     

Drug delivery system of hepatocyte growth factor for the treatment of vocal fold scarring in a canine model

OBJECTIVES: Vocal fold scarring remains a therapeutic challenge. Previous studies have indicated that hepatocyte growth factor (HGF), a strong antifibrotic element, has therapeutic potential for restoring scarred vocal folds. To enhance the effect of HGF in vivo, we developed a novel drug delivery system (DDS) in which HGF is embedded in gelatin hydrogel and continuously released over a period of 2 weeks. In the present study we investigated the therapeutic efficacy of the HGF DDS on vocal fold scarring by using a canine model. METHODS: The vocal folds of 8 beagles were unilaterally scarred by stripping the entire layer of the lamina propria. The contralateral vocal folds were kept intact as normal controls. One month after the procedure, hydrogels (0.5 mL) containing 1 microg of HGF were injected into the scarred vocal folds of 4 dogs (HGF-treated group), whereas hydrogels containing saline solution were injected in the other 4 dogs (sham group). Histologic and vibratory examinations were completed for each group 6 months after the initial surgery. RESULTS: The excised larynx experiments showed significantly better vibration in terms of mucosal wave amplitude and glottal closure in the HGF-treated group compared to the sham group. Histologic evaluation of the vocal folds indicated remarkable reduction in collagen deposition and tissue contraction, with favorable restoration of hyaluronic acid and elastin in the HGF-treated group. CONCLUSIONS: The present findings suggest that the novel HGF DDS may provide favorable effects in restoring the vibratory properties of scarred vocal folds.     

Favorable Vocal Fold Wound Healing Induced by Platelet-Rich Plasma Injection

Objectives

To introduce a new injection material for vocal fold diseases, which could be readily translated to clinical practice, we investigated the effectiveness of platelet-rich plasma (PRP) injection on the injured vocal fold in terms of histological recovery.

Methods

Blood samples were drawn from New Zealand White rabbits and PRP was isolated through centrifugation and separation of the samples. Using a CO₂ laser, we made a linear wound in the 24 vocal fold sides of 12 rabbits and injected each wound with PRP on one vocal fold side and normal saline (NS) on the other. Morphologic analyses were conducted at 2, 4, and 12 weeks after injection, and inflammatory response, collagen deposit, and changes in growth factors were assessed using H&E and masson trichrome (MT) staining and western blot assay.

Results

PRP was prepared in approximately 40 minutes. The mean platelet concentration was 1,315,000 platelets/mm³. In morphological analyses, decreased granulation was observed in the PRP-injected vocal folds (P<0.05). However, the irregular surface and atrophic change were not difference. Histological findings revealed significant inflammation and collagen deposition in NS-injected vocal folds, whereas the PRP-injected vocal folds exhibited less (P<0.05). However, the inflammatory reaction and fibrosis were not difference. In western blot assay, increased amounts of growth factors were observed in PRP-injected vocal folds.

Conclusion

Injection of injured rabbit vocal folds with PRP led to improved wound healing and fewer signs of scarring as demonstrated by decreased inflammation and collagen deposition. The increased vocal fold regeneration may be due to the growth factors associated with PRP.     

Autologous fat augmentation of the vocal fold with basic fibroblast growth factor: Computed tomographic assessment of fat tissue survival after augmentation

Conclusion: The volume of fat tissue loss after vocal fold augmentation can be decreased when augmentation is performed with addition of basic fibroblast growth factor (b-FGF). Objectives: The effectiveness of augmentation is easily decreased due to absorption. Canine experiments have confirmed that the decreased effectiveness caused by absorption after augmentation can be reduced by administering low-concentration b-FGF. Clinical application was trialed after acquiring approval from the institutional clinical review committee. Method: Autologous fat tissue with b-FGF was injected into the vocal folds in cases of unilateral vocal cord paralysis. This study compared fat tissue survival after injection by assessing images from computed tomography (CT). Results: Assessments using CT revealed that the decrease in volume of injected fat tissue was smaller in cases treated using b-FGF than in cases using the conventional method. No severe complications were encountered using this method.     

Influence of aging on hyaluronic acid concentration in the vocal folds of female rats

The vibration of the vocal fold lamina propria is an important factor involved in vocal production and aging may change the amount of hyaluronic acid in the vocal fold leading to dysphonia.AimsThis study compares the concentration of hyaluronic acid in vocal folds of aged and young female rats. Study design: experimental.Materials and MethodsWe used the vocal cords of 13 female rats divided into two groups: five aged rats and eight young ones. The tissue concentration of hyaluronic acid was determined using the fluorimetric method with the hyaluronic acid binding-protein coated on plates of enzyme-linked immunosorbent assay (ELISA), conjugated with biotin. Europium-labeled streptavidin was added and, after europium release with the use of enhancement solution, the final fluorescence was measured in a fluorometer.ResultsWe found the following concentrations of hyaluronic acid in vocal fold according to the group: 581.7 ng/mg in old female rats and 1275.6 ng/ mg in young female rats. Statistical analysis showed differences between groups.ConclusionsThe vocal folds of old female rats have a lower concentration of hyaluronic acid when compared to such concentration on the vocal folds of young female rats.     

Chronic vocal fold scar restoration with hepatocyte growth factor hydrogel

Objectives/Hypothesis:

Therapeutic challenges exist in the management of vocal fold scarring. We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the management of acute phase vocal fold scarring using a novel hydrogel‐based HGF drug delivery system (DDS). However, the effect of HGF on matured vocal fold scarring remains unclear. The current study aims to investigate the effect of HGF‐DDS on chronic vocal fold scarring using a canine model.

Study Design:

Animal model.

Methods:

Vocal folds from eight beagles were unilaterally scarred by stripping the entire layer of the lamina propria; contralateral vocal folds were kept intact as normal controls. Six months after the procedures, hydrogels (0.5 mL) containing 1 μg of HGF were injected into the scarred vocal folds of four dogs (HGF‐treated group). Hydrogels containing saline solution were injected into the other four dogs (sham group). Histological and vibratory examinations on excised larynges were completed for each group 9 months after the initial surgery.

Results:

Experiments conducted on excised larynges demonstrated significantly better vibrations in the HGF‐treated group in terms of mucosal wave amplitude. Although phonation threshold pressure was significantly lower in the HGF‐treated group compared with the sham group, no significant differences were observed in the normalized glottal gap between HGF‐treated and sham groups. Histological examinations of the HGF‐treated vocal folds showed reduced collagen deposition and less tissue contraction with favorable restoration of hyaluronic acid.

Conclusions:

Results suggest that administration of HGF may have therapeutic potential in the treatment of chronic vocal fold scarring. Laryngoscope, 2010     

Vocal fold injection: review of indications, techniques, and materials for augmentation

Vocal fold injection is a procedure that has over a 100 year history but was rarely done as short as 20 years ago. A renaissance has occurred with respect to vocal fold injection due to new technologies (visualization and materials) and new injection approaches. Awake, un-sedated vocal fold injection offers many distinct advantages for the treatment of glottal insufficiency (vocal fold paralysis, vocal fold paresis, vocal fold atrophy and vocal fold scar). A review of materials available and different vocal fold injection approaches is performed. A comparison of vocal fold injection to laryngeal framework surgery is also undertaken. With proper patient and material selection, vocal fold injection now plays a major role in the treatment of many patients with dysphonia.     

Hepatocyte growth factor and its receptor c-met in rat and rabbit vocal folds

Vocal fold fibrotic scar is characterized by fibrosis of the lamina propria and epithelium, and is difficult to treat. Hepatocyte growth factor (HGF) has antifibrotic activity and has received attention as a possible therapeutic alternative to treat fibrosis. In this study, in order to clarify whether HGF can be involved in vocal fold scarring, we examined the existence of HGF and its receptor, c-Met, in rat vocal folds, and then the activity of HGF in rabbit injured vocal folds, using immunohistochemistry and enzyme-linked immunosorbent assay. We found HGF and c-Met on epithelial cells and gland cells of the rat vocal folds. On the injured vocal folds of rabbits, little HGF was observed immediately after injury, but prominent activity occurred simultaneously with reepithelialization of the vocal fold mucosa on days 10 to 15. The activity of HGF was observed on fibroblasts in the lamina propria, as well as the epithelium. It is suggested that HGF in the vocal folds is produced by the fibroblasts and delivered to the epithelium. The implication of these findings is that HGF is involved in wound healing of the vocal fold, and may provide an alternative approach in preventing and treating vocal fold scarring.     

Results with collagen injection into the vocal folds for medialization

PURPOSE OF REVIEW: This review outlines the indications, surgical techniques and follow-up, with results, for current collagen use. RECENT FINDINGS: Micronized AlloDerm (Cymetra) is a presently available injectable substance made from human collagen and elastin particles. A mean follow-up of 8-10.5 months showed lasting results after injection for vocal fold immobility. Collagen injection is one possible method for treating a vocal fold scar - or sulcus -vergeture by medialization of one or both of the scarred vocal folds. Collagen injection laryngoplasty is presently the treatment of choice for presbyphonia if speech therapy is insufficient. Collagen injection for Parkinson-related dysphonia is an effective temporary method of subjectively improving voice and speech in selected patients. Laryngeal collagen injection can also permit further medialization of one or both vocal folds after medialization thyroplasty. SUMMARY: Injection laryngoplasty with micronized AlloDerm, a presently available homologous collagen, remains a suitable option for the treatment of vocal fold immobility with a moderate gap. Collagen injection is also efficient for sulcus vergetures, scars and presbyphonia, and can help in cases of Parkinson's disease. Complications are uncommon but patients must be advised that the stability of results is unpredictable. Collagen injection can be repeated and does not prevent other surgical solutions.     

人羊膜上皮细胞移植用于兔损伤声带组织修复的初步研究

目的 研究人羊膜上皮细胞(human amniotic epithelial cells,hAEC)移植入兔声带损伤组织内的生长分布特点,探索hAEC促进声带损伤后修复再生的潜能.方法 分离和培养hAEC,慢病毒增强型绿色荧光蛋白(1entivirus enhanced green fluorescent protein,Lenti-EGFP)基因转染作标记.建立深及声韧带的兔声带损伤模型,设hAEC移植组(13侧声带)、损伤对照组(13侧声带)及正常对照组(4侧声带).荧光显微镜下连续观察hAEC在声带内的存活、分布情况,应用HE染色和免疫组化染色分析胶原、纤维连接蛋白等主要细胞外基质在损伤后3个月时的含量及分布.结果 hAEC原代培养6 d后呈铺路石样生长,植入声带损伤组织后可在固有层内持续存活2个月,细胞呈纵向排列,有趋向性.声带损伤2个月时免疫荧光显示hAEC移植组兔肌细胞标志结蛋白荧光阳性,提示hAEC向肌细胞分化;同时Ⅲ型胶原荧光阳性,提示hAEC植入后具有分泌Ⅲ型胶原功能.光镜观察见hAEC移植后3个月兔胶原纤维密度和排序较损伤对照组改善,但未及正常;免疫组化染色示hAEC移植组纤维连接蛋白含量和分布介于损伤对照组和正常对照组之间.结论 hAEC可在异种动物声带损伤组织内持续存活、生长,并有向声带组织分化和分泌部分细胞外基质的潜能,可能促进声带损伤后的修复再生.

Abstract：

Objective To investigate the survival, growth and distribution of human amniotic epithelial cells (hAEC) after injected into injured rabbit vocal folds, in addition, to assess the ability of hAEC to affect the components of lamina propria extracellular matrix (ECM) and prevent vocal fold scarring.Methods hAEC were isolated from human amnion and marked by Lenti-EGFP. Fifteen New Zealand rabbits were used for this experiment. EGFP-hAEC was injected into the left injured vocal folds in thirteen rabbits, and the contralateral thirteen vocal folds experienced an injured procedure only (" injured untreated control"), and four vocal folds were left as untreated controls. The survival, distribution, differentiation potential and secretion function of hAEC were examined by immunofluorescence method. HE staining and immunohistochemical staining were performed for the evaluation of collagen and fibronectin respectively.Results hAEC showed a cobblestone-like growth. After implanted into the injured vocal folds, hAEC could survive in vocal fold lamina propria for 2 months. The immunofluorescence analysis showed the evidence of hAEC differentiation into muscle cells as well as secretion the ECM protein. Three months postoperatively, the density of collagen was higher in the injured untreated control folds than that in the injured vocal folds injected with hAEC and the untreated controls. Besides, the content of fibronectin in the injured untreated control group was significantly increased. Conclusions hAEC survived in the vocal folds lamina propria,and had the potentiality to differentiate into vocal folds tissue and secret some ECM components. The histological improvement caused by the injected cells demonstrate that hAEC had the ability to promote the repairment and regeneration of injured vocal folds.     

人羊膜上皮细胞移植用于兔损伤声带组织修复的初步研究

目的 研究人羊膜上皮细胞(human amniotic epithelial cells,hAEC)移植入兔声带损伤组织内的生长分布特点,探索hAEC促进声带损伤后修复再生的潜能.方法 分离和培养hAEC,慢病毒增强型绿色荧光蛋白(1entivirus enhanced green fluorescent protein,Lenti-EGFP)基因转染作标记.建立深及声韧带的兔声带损伤模型,设hAEC移植组(13侧声带)、损伤对照组(13侧声带)及正常对照组(4侧声带).荧光显微镜下连续观察hAEC在声带内的存活、分布情况,应用HE染色和免疫组化染色分析胶原、纤维连接蛋白等主要细胞外基质在损伤后3个月时的含量及分布.结果 hAEC原代培养6 d后呈铺路石样生长,植入声带损伤组织后可在固有层内持续存活2个月,细胞呈纵向排列,有趋向性.声带损伤2个月时免疫荧光显示hAEC移植组兔肌细胞标志结蛋白荧光阳性,提示hAEC向肌细胞分化;同时Ⅲ型胶原荧光阳性,提示hAEC植入后具有分泌Ⅲ型胶原功能.光镜观察见hAEC移植后3个月兔胶原纤维密度和排序较损伤对照组改善,但未及正常;免疫组化染色示hAEC移植组纤维连接蛋白含量和分布介于损伤对照组和正常对照组之间.结论 hAEC可在异种动物声带损伤组织内持续存活、生长,并有向声带组织分化和分泌部分细胞外基质的潜能,可能促进声带损伤后的修复再生.     

Injection of basic fibroblast growth factor for unilateral vocal cord paralysis*

Objective: Unilateral vocal cord paralysis (UVCP) not only induces severe dysphonia, but aspiration as well. Although laryngeal framework surgery is usually performed to treat this condition, the procedure is not tolerated by some patients. In the previous study, basic fibroblast growth factor (bFGF) injections for vocal cord scarring and sulcus have been reported to provide favorable outcomes while being minimally invasive. In this study, the authors retrospectively investigated phonological outcomes after bFGF injection in patients with UVCP.

Methods: This study was registered in University hospital Medical Information Network – Clinical Trials Registry (UMIN000019347). Nineteen patients with unilateral cord paralysis were treated with bFGF injection. The treatment regimen involved a single injection of 50?μg of bFGF into the muscle layer. More than six months after the injection, aerodynamic and acoustic outcomes were examined.

Results: The voice handicap index, maximum phonation time, mean airflow rate, and pitch range improved significantly after injection of bFGF. No sex-related differences were observed in any phonological parameter.

Conclusion: bFGF injection, an easy method and suitable as an office procedure, significantly improved the hoarseness caused by UVCP. It is expected to be widely adopted and effective adjunctive drugs, and procedures are anticipated to be developed.     

Effect of sugarcane biopolymer gel injected in rabbit vocal fold

IntroductionAlterations in the vocal folds that involve volume reduction and glottal closure failure result in exaggerated air escape during speech. For such situations, the use of implants or grafts of different materials has been proposed.ObjectiveTo define the effect of sugarcane biopolymer gel when implanted in the vocal folds of rabbits.MethodsThis was an experimental study. The vocal folds of rabbits injected with sugarcane biopolymer and saline solution were histologically evaluated after 21 and 90 days.ResultsMild to moderate inflammation and increased volume were observed in all vocal folds injected with biopolymer, when compared to controls. There were no cases of necrosis or calcification.DiscussionThis study showed higher inflammatory reaction in cases than in controls and biopolymer biointegration to the vocal fold. This fibrogenic response with absence of epithelial repercussions suggests that the biopolymer in its gel form can be bioactive and preserve the normal vibratory function of the epithelium.ConclusionWe show that in spite of producing an inflammatory reaction in vocal fold tissues, the material remained in vocal fold throughout the study period.     

自体脂肪间充质干细胞移植促进声带修复再生的实验研究

目的 探讨自体脂肪间充质干细胞移植入损伤声带后的生长分布及对声带固有层及其主要细胞外基质变化的影响特点.方法 对34只实验用兔(68侧声带)的53侧声带进行全麻支撑喉镜下声带锐性损伤.分离培养、鉴定及定向诱导20只实验用兔脂肪间充质干细胞.将自体脂肪间充质干细胞植入20侧损伤声带后,示踪观察脂肪间充质干细胞在声带固有层内的生长分布;同时以单纯支架(胶原或透明质酸凝胶)植入18侧受损声带(胶原10侧,透明质酸8侧)及单纯损伤15侧声带作为对照组.术后15 d～12个月时采用HE染色、Masson染色、Alcian Blue染色及免疫组化染色观察声带形态学变化及声带固有层胶原、透明质酸、纤维连接蛋白的含量及分布变化.结果 脂肪间充质干细胞呈梭形贴壁生长,具有多向分化潜能,植入损伤兔声带后持续分布于声带固有层.损伤声带在脂肪间充质于细胞植入6个月时形态接近正常,12个月时部分组织学结构类似正常;声带细胞外基质中的胶原于植入3个月内含量有增高趋势,无序分布于固有层,后逐渐减少至正常水平附近,12个月时部分分布略显不规则;透明质酸于植入40 d含量亦有增高趋势,分布于固有层各层,6个月含量减至正常水平附近,局限于固有层浅中层;纤维连接蛋白于植入后始终在固有层内散在分布,含量在40 d内有增高趋势,后逐渐减少,12个月时含量接近正常.单纯声带损伤3个月后局部开始出现瘢痕挛缩,以胶原纤维为主的大量纤维组织增生,12个月时仍紊乱分布于声带固有层各层.单纯支架植入组变化介于二者之间.结论 脂肪间充质干细胞植入兔损伤声带后具有促进声带细胞外基质分泌、合理分布及部分有序化排列的功能,具有促进声带修复再生的作用.     

Regeneration of aged vocal folds with basic fibroblast growth factor in a rat model: a preliminary report

Aged vocal folds have been reported to have dense collagen deposition and decreased hyaluronic acid (HA) in the lamina propria. These characteristics are thought to contribute to vocal problems that occur with age (presbyphonia). To restore better viscoelasticity to aged vocal folds, an intervention that might increase HA and decrease collagen production from aged vocal fold fibroblasts would appear to be a potentially useful approach. Our previous in vitro study has revealed that basic fibroblast growth factor (bFGF) consistently stimulates HA production and decreases collagen production from aged rat vocal fold fibroblasts. The present in vivo study examined the effects of intracordal injection of bFGF into aged rats' vocal folds in terms of restoration of HA and collagen distribution in the lamina propria. We injected bFGF transorally into the lamina propria of (unilateral) vocal folds. The injection was repeated 4 times weekly, and rats were painlessly sacrificed 1 week, 1 month, and 2 months after the final injection. Histologic examination revealed that bFGF significantly increased the HA content of the lamina propria up to 2 months, but showed no effect on collagen, even after 2 months. Because it might take longer for excessive collagen to be degraded, further studies are necessary to clarify the long-term effect on collagen. A drug delivery system for bFGF also needs to be developed to maximize its effect in the future. The present study suggested at least a positive effect of bFGF in restoring the HA content in the aged vocal fold lamina propria.     

Prevention of vocal fold scarring by topical injection of hepatocyte growth factor in a rabbit model

OBJECTIVES/HYPOTHESIS: Vocal fold scarring disrupts the layer structure of the vocal fold lamina propria that is essential for optimal mucosal vibration. Prevention of vocal fold scarring remains challenging. Hepatocyte growth factor (HGF) has strong antifibrotic activity. The authors' previous studies have found that HGF stimulates hyaluronic acid production and suppresses collagen production from vocal fold fibroblasts, suggesting that HGF has therapeutic potential in prevention of vocal fold scarring. The present study aimed to demonstrate the effects of HGF on vocal fold scarring in an in vivo rabbit model. STUDY DESIGN: Animal experiment. METHODS: The vocal fold mucosa was stripped unilaterally in 20 rabbits, then HGF or saline (sham-treated group) was immediately injected into the injured site. At 6 months after the procedure, histological, rheological, and physiological examinations of vibratory behavior were completed. RESULTS: Histological examination revealed excessive collagen deposition and disorganized elastin in the sham-treated group, whereas the HGF-treated group presented with better wound healing exhibiting less collagen deposition. Contraction of the injured vocal folds observed in the sham-treated group did not occur in the HGF-treated group. Rheological data indicated that the HGF-treated vocal folds were less stiff and viscous compared with the sham-treated group. Mucosal vibration of HGF-treated vocal folds appeared much better than the sham-treated group in terms of phonation threshold pressure, vocal efficiency, mucosal wave amplitude, and glottal closure. CONCLUSION: Hepatocyte growth factor proved to be useful in preventing vocal fold scarring and maintaining viscoelastic shear properties of the vocal fold.     

Voice and vocal fold position in men with unilateral vocal fold paralysis

The paralyzed vocal fold positioning and the degree of dysphonia are important inputs when one is deciding upon treatment options for unilateral vocal fold paralysis (UVFP).ObjectiveTo check voice characteristics and paralyzed vocal fold position in men with UVFP.Materials and MethodsThis is a retrospective historical cross-sectional cohort study, with data from 24 men with UVFP with mean age of 60.7 years, submitted to voice assessment by three speech therapists and three ENT physicians used laryngeal images to classify the position of the paralyzed vocal fold.ResultsThe paralyzed vocal fold was found in the paramedian position in 45.83% of the cases; in the intermediary position in 25%; lateral in 20.83%, and it was in the median position in 4.16%; the dysphonia resulting from the UVFP was characterized by moderate hoarseness, roughness and stress in the voice; breathiness (most had severe breathiness); weakness and instability(mostly mild); the position of the paralyzed vocal fold had a significant influence on the general degree of vocal deviation.ConclusionThe general degree of dysphonia is associated with the paralyzed vocal fold position; dysphonia is characterized by hoarseness, breathiness, roughness and stress of moderate to severe levels.