Treatment Of Vocal Fold Scarring Research Articles

Prospective Outcomes After Serial Platelet-Rich Plasma (PRP) Injection in Vocal Fold Scar and Sulcus.

Vocal fold scar and sulcus pose significant treatment challenges with no current optimal treatment. Platelet-rich plasma (PRP), an autologous concentration of growth factors, holds promise for regenerating the superficial lamina propria. This study aims to evaluate the potential benefits of serial PRP injections on mucosal wave restoration and vocal function. In a prospective clinical trial across two institutions, patients with vocal fold scar underwent four serial PRP injections, one month apart. Blinded independent laryngologists and expert listeners used pretreatment and one-month post-fourth injection videostroboscopy and CAPE-V assessments to evaluate mucosal wave and voice quality changes, respectively. Additionally, patient reported outcome measures (PROMs) were evaluated. In the study, 15 patients received 55 PRP injections without adverse effects. Eight patients (53.3%) had mild, three patients (20%) had moderate, and four patients (26.7%) had severe scar. There was an average reduction of 8.7 points in post-treatment VHI-10 scores (p = 0.007). The raters observed an improvement in post-treatment voice in 73.4% of cases, and CAPE-V scores showed a reduction of 18.8 points on average (p = 0.036). The videostroboscopic VALI ratings showed an improvement in mucosal wave rating from 2.0 to 4.0. On average, the raters perceived the post-PRP exams to be better in 56.7% of cases. PRP has been validated as a safe autologous option for treatment of vocal fold scar. While results for mucosal wave and voice quality varied, there was a consistent improvement in PROMs. Level 3: Prospective cohort study, with blinded analysis Laryngoscope, 2024.

5-Fluorouracil for Treatment of Vocal Fold Scar

Vocal fold (VF) scar can result from trauma, neoplasm, inflammatory processes, congenital causes, surgery and other etiologies. In general, once the vibratory margin of the VF has been scarred, it has not been possible to return VF function to normal; but often it can be improved. The drug 5-fluorouracil (5-FU) is a pyrimidine antimetabolic that has many clinical applications ranging from systemic chemotherapy to topical treatment of actinic keratosis and basal cell carcinoma of the skin. Local injection with 5-FU also has been used for hypertrophic scar and keloids. 5-FU was shown to have benefit in animal models of VF scar and subglottic stenosis. The present study aimed to evaluate the effect of 5-FU injection on VF vibratory function in patients with VF scar. Outcomes of 5-FU injection were compared to controls injected with dexamethasone. Adult voice center patients who had undergone VF injection with dexamethasone or a series of three 5-FU injections for treatment of VF scar were included in the study. Postoperative outcomes included percentage of subjects demonstrating improvement after injection, change in scar size, glottic closure, and VF stiffness, as well as digital image analysis measurements of mucosal wave. Outcomes were compared between subjects who received 5-FU and those who received dexamethasone. There were 58 VFs injected with 5-FU and 58 historical controls injected with dexamethasone. Baseline subject characteristics and etiology of scar did not differ significantly between the 5-FU and dexamethasone cohorts, except that scar size was greater in the 5-FU group and mucosal wave was worse at baseline. After a series of three 5-FU injections, 61.22% improved, 8.16% demonstrated no change, and 30.61% worsened. In the dexamethasone cohort, 51.06% improved, 0.00% demonstrated no change, and 48.94% worsened. The response differed significantly between the 5-FU and dexamethasone cohorts, with a greater proportion of subjects who underwent 5-FU injection demonstrating improvement postoperatively. In the 5-FU cohort, 32.76% of subjects previously had undergone and failed dexamethasone injection for VF scar: and within that group 84.21% improved, 5.26% demonstrated no change, and 10.53% worsened following 5-FU injection. On digital image analysis, the percent improvement in postoperative mucosal wave was significantly greater in the 5-FU cohort compared to the dexamethasone group, which demonstrated a worsening of mucosal wave. A series of three intralesional injections with 5-FU outperformed dexamethasone for improving mucosal wave in patients with VF scar. A prior failed trial of dexamethasone injection predicted a favorable response to 5-FU. Further research is encouraged to confirm or refute these findings.

Establishment and characterization of immortalized human vocal fold fibroblast cell lines.

Vocal fold scarring is abnormal scar tissue in the lamina propria layer of the vocal fold. To facilitate investigation of vocal fold scarring, we established and characterized immortalized human vocal fold fibroblast (iHVFF) cell lines. Human vocal fold fibroblasts were immortalized by introducing Simian virus 40 large T antigen (SV40TAg) by transfection. Successfully transfected fibroblasts were sorted using flow cytometry. Immunofluorescence cytochemistry and western blot were applied to analyze the expression of fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Cell proliferation rate was measured by CCK-8 assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA expression level. The iHVFFs continued to proliferate for more than 30 generations and appeared spindle-shaped. The expression of Vimentin and α-SMA were detected in both iHVFFs and primary fibroblasts, and enhanced expression of FAP was observed in iHVFFs. Furthermore, iHVFFs exhibited an increased proliferative capability compared with the primary fibroblasts. RT-qPCR results suggested that collagen type III alpha 1 chain (COL3A1), interleukin-6, cyclooxygenase 2 (COX2), hyaluronan synthase 2 (HAS2), hepatocyte growth factor (HGF) in the iHVFFs significantly increased, whereas transforming growth factor-β1 (TGF-β1), elastin and matrix metallopeptidase-1 (MMP-1) expression significantly downregulated. No differences in mRNA expression of α-SMA, fibronectin and collagen type I alpha 2 chain (COL1A2) were noted between iHVFFs and primary fibroblasts. iHVFFs can be used as a novel tool cell for future researches on the mechanisms of pathogenesis and treatment of vocal fold scarring.

Ultrafast laser surgery probe for sub-surface ablation to enable biomaterial injection in vocal folds

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting.

Phonation Threshold Pressure as a Unique Outcome Measure of Phonatory Physiology Changes Following Submucosal Saline Injection for Vocal Fold Scarring

Purpose: This study aimed to describe the utility of phonation threshold pressure (PTP) measurement as an additional outcome measure for changes in vocal fold vibration secondary to submucosal saline injection in the case of an individual with idiopathic vocal fold scarring. Method: An 8-week program of voice therapy, followed by submucosal saline infusion, was administered, using multiple outcome measures to assess voice quality, effort, and function in a 38-year-old woman with idiopathic bilateral vocal fold scarring. Transoral rigid video-endoscopy with stroboscopy in conjunction with the Stroboscopy Evaluation Rating Form provided measures of the vibratory characteristics of the vocal folds (amplitude, mucosal wave, nonvibratory portion, edge smoothness, and straightness). Auditory-perceptual measures were obtained using the Consensus Auditory-Perceptual Evaluation of Voice. Acoustic measures included jitter (%local), shimmer (%local), harmonics-to-noise ratio (dB), and Cepstral Spectral Index of Dysphonia. Additionally, PTP was measured 1 day prior to, and 1 month after, saline infusion. Results: Acoustic, auditory-perceptual, and stroboscopic variables suggested minimal change to the vibratory properties of the vocal folds in response to submucosal saline infusion for the treatment of vocal fold scarring. PTP measurements across the patient's frequency range, however, revealed a marked decrease post infusion. This was consistent with the patient's report of improved functioning and her request for repeat saline infusion. Conclusion: These results are consistent with the possibility of using PTP as an independent means of quantifying changes in phonatory physiology across the frequency range in patients with vocal fold scarring. Supplemental Material: https://doi.org/10.23641/asha.21313725

Cryotherapy Modifies Extracellular Matrix Expression of Vocal Fold in Rat Models

Vocal fold (VF) scarring is the major cause of voice disorders. Cryotherapy is an effective anti-scarring therapy for skin lesions. The aim of this study was to explore the anti-scarring potential of cryotherapy in vocal folds. The extracellular matrix (ECM) mRNA expression of cryotherapy on normal VF tissue and the histologic results of cryotherapy on vocal fold healing were studied. Fifteen rats were introduced cryotherapy on the normal VF bilaterally and were harvested for real-time polymerase chain reaction (RT-PCR) analysis for collagen I, collagen III, TGFβ1, decorin, fibronectin and HAS1 at 1 day, 3 days and 7 days. Ten rats were unilaterally injured by stripping lamina propria and immediately treated with or without cryotherapy and were harvested at 2 months for histological and immunohistochemical analysis. Regenerative effect of cryotherapy was validated of ECM gene expression. Histological and immunohistochemical analysis showed significantly increased hyaluronan, decreased collagen, and increased decorin deposition in injury-cryotherapy cohort compared with injury control cohort and normal control cohort. Cryotherapy may provide an optimal environment for vocal fold tissue regeneration. The results of the present investigation suggest that cryotherapy has therapeutic potential in prevention and treatment of vocal fold scarring.

Safety of Platelet-Rich Plasma Subepithelial Infusion for Vocal Fold Scar, Sulcus, and Atrophy.

To demonstrate the safety profile of platelet-rich plasma (PRP) as an injectable therapeutic for the treatment of vocal fold scarring and atrophy. Preliminary report on a prospective clinical trial of patients with vocal fold scar or atrophy undergoing unilateral vocal fold subepithelial infusion with autologous PRP. Enrolled patients underwent four subepithelial injections spaced 1 month apart. Adverse events were assessed peri and post-injection at each session. Patient-reported outcomes were collected at every visit using the Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI) questionnaires. Twelve patients underwent unilateral vocal fold injection with autologous PRP prepared according to Eclipse PRP® system protocol. Forty-three injections were performed using a peroral or percutaneous approach. An average of 1.57 ± 0.4 cc (range 0.6-2.0 cc) injectate was used. All patients tolerated the procedure without difficulty or peri-procedural complications. The average duration of follow-up was 3.6 ± 1.8 months. No significant inflammatory reactions or adverse events were seen to date. There was statistically significant improvement in patient-reported outcomes at the 3 month follow up (n=9) follow-up (mean ΔVHI-10=10.8, p < 0.001, mean ΔVFI=18.9, p=0.01, t test, paired two sample for means, two-tail). All nine patients who completed the series of four injections subjectively (yes/no) reported they were satisfied with the results. This prospective study cohort demonstrated a favorable safety profile, with no adverse events or peri-procedural complications. Subjective improvements in vocal quality and reduction in vocal fatigue need to be clinically correlated with further study. 4 Laryngoscope, 133:647-653, 2023.

Core-Shell Microfibers via Bioorthogonal Layer-by-Layer Assembly.

A new technique is described for the construction of core-shell microfibers for biomedical applications. Fibrous scaffolds were fabricated by electrospinning, followed by covalent layer-by-layer deposition based on the rapid bioorthogonal reaction between s-tetrazines (Tz) and trans-cyclooctenes (TCOs). Electrospun poly(ε-caprolactone) (PCL) scaffolds were subjected to surface modifications to install tetrazine groups. The scaffolds were iteratively submerged in aqueous solutions of TCO-modified hyaluronic acid (HA-TCO) and tetrazine-modified hyaluronic acid (HA-Tz), resulting in the controlled growth of a cross-linked HA gel around individual microfibers. Integrin-binding motifs were covalently attached to the surface of the microfibers using TCO-conjugated RGD peptide. The scaffolds fostered the attachment and growth of primary porcine vocal fold fibroblasts without a significant induction of the myofibroblast phenotype. Stimulation with transforming growth factor beta (TGF-β) moderately enhanced fibroblast activation, and inhibition of the Rho/ROCK signaling pathway using Y27632 further decreased the expression of myofibroblastic markers. The bioorthogonally assembled scaffolds with a stiff PCL core and a soft HA shell may find application as therapeutic implants for the treatment of vocal fold scarring.

Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells\u2014first phase I/II human clinical study

BackgroundVocal fold (VF) scarring, caused by surgery or inflammation, often results in severe voice problems or aphonia. Effective lasting treatment is lacking. Previous in vitro and in vivo animal studies reported positive effects on VF scar resolution with mesenchymal stromal cell (MSC) implantation. The principal aim of this study was to examine safety aspects and secondly treatment efficacy vocal fold function in patients with VF scarring and severe voice problems.MethodsIn this open-label phase I/II study, 16 patients were treated with surgical scar resection followed by injection of autologous MSCs (0.5–2 × 106 MSCs/patient). Patients were monitored 1 year for serious adverse events (SAE) or minor complications. Therapeutic efficacy on treated VFs was evaluated by measurement of VF vibrations using high-speed laryngoscopy (HSL) and phonation pressure threshold (PTP) for elasticity and VF function. Patients self-reported voice change using the Voice Handicap Index (VHI).ResultsNo SAE or minor side effects were reported. Video ratings of VF vibrations and digitized analysis of HSL and PTP were significantly improved for 62–75% of the patients (depending on parameter). Two patients showed deteriorated VF vibrations, but improved PTP. VHI was significantly improved in 8 patients, with the remaining experiencing no significant change.ConclusionsThe results indicate that local injection of autologous MSC into scarred VFs with severe voice problems may offer a safe and feasible therapeutic option. VF vibration and elasticity were improved in approximately two thirds of treated patients.This clinical study is registered in clinicaltrials.gov (ID: NCT01981330). Retrospective registration of first patient (20130511). https//: register.clinicaltrials.gov/.

Cryotherapy has antifibrotic and regenerative effects on human vocal fold fibroblasts.

Vocal fold scarring remains a major treatment challenge, and scar prevention without residual lesions remains a dilemma. Cryotherapy has shown cosmetic outcomes on skin lesions with minimal scarring. The aim of this study was to clarify the beneficial effects of cryotherapy for the prevention and the treatment of vocal fold scarring. In vitro. Primary cultures of human vocal fold fibroblasts (VFFs) were used in this study. Myofibroblast differentiation was stimulated by transforming growth factor β1 (TGF-β1). We mimicked the cryotherapy effect on vocal fold healing in vivo by freezing VFFs ± TGF-β1 in vitro. The influence of freezing on cell viability, proliferation, migration, and contractile properties were analyzed. The expression of collagen I, collagen III, fibronectin, TGF-β1, matrix metallopeptidase 1 (MMP1), hyaluronan synthase 1 (HAS1) were investigated by real-time polymerase chain reaction (RT-PCR), and the expression of alpha smooth muscle actin (α-SMA) and decorin were investigated by RT-PCR and Western blot. Freezing was found to modify extracellular matrix (ECM) synthesis and differentiation of VFFs. Expression of collagen I, collagen III, fibronectin, α-SMA, and TGF-β1 was downregulated, and MMP1 was upregulated in VFFs + TGF-β1 (myofibroblast) by freezing. HAS1 and decorin were upregulated in both VFFs ± TGF-β1 by freezing. Freezing VFFs + TGF-β1 (myofibroblast) with fast thawing had a lower expression of α-SMA when compared with slow thawing. Freezing reduced the migration and collagen contraction of VFFs + TGF-β1 (myofibroblast). Cryotherapy induces antifibrotic and regenerative ECM alterations in VFFs. These data provide insight into the prevention and the treatment of vocal fold scarring with cryotherapy in phonomicrosurgery. NA Laryngoscope, 129:E143-E150, 2019.

Adipose-Derived Mesenchymal Stromal Cells Persist in Tissue-Engineered Vocal Fold Replacement in Rabbits.

Cell therapies using mesenchymal stromal cells (MSCs) have been proposed as a promising new tool for the treatment of vocal fold scarring. However, the mechanisms by which MSCs promote healing as well as their duration of survival within the host vocal fold have yet to be defined. The aim of this work was to assess the persistence of embedded MSCs within a tissue-engineered vocal fold mucosal replacement in a rabbit model of vocal fold injury. Male rabbit adipose-derived MSCs were embedded within a 3-dimensional fibrin gel, forming the cell-based outer vocal fold replacement. Four female rabbits underwent unilateral resection of vocal fold epithelium and lamina propria and reconstruction with cell-based outer vocal fold replacement implantation. Polymerase chain reaction and fluorescent in situ hybridization for the sex-determining region of the Y chromosome (SRY-II) in the sex-mismatched donor-recipient pairs sought persistent cells after 4 weeks. A subset of implanted male cells was detected in the implant site at 4 weeks. Many SRY-II-negative cells were also detected at the implant site, presumably representing native female cells that migrated to the area. No SRY-II signal was detected in contralateral control vocal folds. The emergent tissue after implantation of a tissue-engineered outer vocal fold replacement is derived both from initially embedded adipose-derived stromal cells and infiltrating native cells. Our results suggest this tissue-engineering approach can provide a well-integrated tissue graft with prolonged cell activity for repair of severe vocal fold scars.

Migration and Contraction of Fibroblasts from Normal and Scar Vocal Folds with Applications to Wound Healing

Vocal fold scarring has various causes, including inflammation, trauma, radiotherapy and laryngeal surgeries. The treatment for vocal fold scarring is a challenge in Laryngology practice. Scars disrupt the layered structure and induce disorder in the lamina propria extracellular matrix, which causes significant change in vocal fold biomechanics, resulting in voice disorders that often compromise patient quality of life. Vocal fold fibroblasts are responsible for synthesis of the extracellular matrix, playing a key role in support of the lamina propria in normal and diseased conditions. During tissue injury, vocal fold fibroblasts become activated and differentiate into myofibroblasts, initiating contractile forces that facilitate wound healing. The correct balance between contraction and extracellular matrix deposition is required for optimal healing. Using a scratch assay with live-cell time lapse microscopy and traction force microscopy, we analyze the migration and contraction of fibroblasts from normal and scar human vocal folds during wound healing. As expected, most of the normal and scar vocal fold fibroblasts migrated toward the free area within 24 hours, which is a critical time-point after laryngeal surgeries. Scar vocal fold fibroblasts moved less persistently but in a collective manner whereas normal cells had more persistent and individual patterns of migration. Additionally, scar cells contracted approximately two times more than normal vocal fold fibroblasts. We expect these results to clarify mechanisms of migration and contraction of normal and scar vocal fold fibroblasts. This data may be useful to design experiments that increase or decrease contraction and migration to cause faster healing or reduced scar formation.

Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long-Term Outcomes.

Sulcus vocalis and vocal fold scar involve derangement of the superficial lamina propria of the vocal fold, which results in significant dysphonia. Many options exist for treatment, most of which have unsatisfactory and unpredictable outcomes. Autologous transplantation of temporalis fascia into the vocal fold (ATFV) has the potential to be a better treatment option, but long-term outcomes have not been well studied. Retrospective chart review and patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus vocalis and treated with ATFV with at least 1-year follow-up were included. Voice Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6 months postoperatively. Patients were reached at the time of the study to complete another VHI-10 and a Likert scale survey. The mean decrease in VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P < .001). From preoperation to the time of the study (average 44 months; range, 12-72 months), the VHI decreased 13.53 ( P < .001). Eighty-eight percent of patients reported they would recommend this surgery to others with the same diagnosis. Only 1 minor self-limited complication occurred. Autologous transplantation of temporalis fascia into the vocal fold for the treatment of vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes and high patient satisfaction.

The Ferret as a Surgical Model for Vocal Fold Scar Creation and Treatment.

To develop a vocal fold (VF) scarring procedure in the ferret, characterize the scars histologically, and test the injectability of the lamina propria (LP). Secondarily, to compare laryngeal anatomy of the ferret with rat and rabbit. The larynges of 18 male ferrets were prepared by unilateral scarring, and normal larynges from 6 female Wistar rats and 5 male albino rabbits were used for comparative purposes. For scarring, the right VF were electrocauterized, ablating the entire LP. Prior to harvesting the larynges at 4 and 16 weeks, each ferret was re-anesthetized, and in 3 animals, India ink was injected into the LPs of both normal and scarred VFs. Laryngoscopic methods and instrumentation for precise visualization, scarring, and injection were developed. The scarred VFs had reduced hyaluronic acid and increased collagen type I, III, and fibronectin compared with normal VFs. The 2 timepoints (4 and 16 weeks) differed significantly only in collagen type III level (levels were higher at 4 weeks). Injected ink migrated from scarred LP to muscle layer just beneath the scarred tissue 3 hours after injection. The ferret is a promising species for creation and experimental treatment of vocal fold scar.

Experimental study of autologous fibroblast cell transplantation in the treatment of vocal fold scar

Objective:To study the change characteristics of vocal cords scar after the implantation of autologous fibroblast cells into the vocal cords. Method:Forty New Zealand rabbits were used for the production of vocal fold scar model by creating a unilateral vocal fold wounds, we take the skin tissues of each rabbits and cultured them via enzyme digestion method to obtain autologous fibroblast cells. The models were separated into the experimental group and the control group, the third generation fibroblast cells with CM DIL labeled were then injected into the surrounding area of the vocal fold scar in the experimental group, the survival situation of the injected cells were observed by fluorescence microscopy after 1 week, histological examination was performed after 1 months to observe the morphological changes of vocal fold scar tissues, RT-PCR method was used to measure the expression variation of typeⅠcollagen and type Ⅲ collagen in the vocal cords and the normal vocal cords, respectively. Result:After 1 week of autologous fibroblast transplantation into the vocal folds, the fluorescence labeled cells were observed.1 month after transplantation, the collagen protein in the vocal fold scar tissues was similar to that in the normal vocal folds，the expression of typeⅠcollagen and type Ⅲ collagen in vocal fold scars is similar to those in the normal vocal folds. Conclusion:Autologous fibroblast migration into the vocal cords can survive well inside the vocal cords, and the vocal scar can be recovered to normal vocal cord structure after transplantation of autologous fibroblast cells.

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies.

ObjectivesTherapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring.Data SourcesPubMed, Embase, the Cochrane Library and Google Scholar were searched.MethodsControlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude.ResultsSeven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds.ConclusionThe results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.

Prevention of vocal fold scarring by local application of basic fibroblast growth factor in a rat vocal fold injury model.

Vocal fold scarring, which causes severe hoarseness, is intractable. The optimal treatment for vocal fold scarring has not been established; therefore, prevention of scarring is important. The aim of this study was to clarify the effectiveness of basic fibroblast growth factor (bFGF) for prevention of postsurgical vocal fold scarring. Prospective animal experiments with controls. The vocal folds of Sprague-Dawley rats were injured unilaterally or bilaterally after local application of a 10 μL solution of bFGF. Larynges ware harvested for histological and immunohistochemical examination 2 months postoperation and for quantitative real-time polymerase chain reaction (qRT-PCR) analysis 1 week postoperation. Histological examination showed significantly increased hyaluronic acid and decreased deposition of dense collagen in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. Immunohistochemical examination showed significantly decreased collagen type III deposition in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. qRT-PCR revealed that hyaluronan synthase 2 (Has2), Has3, and hepatocyte growth factor were upregulated in bFGF-treated groups compared with sham-treated group. The current results suggest that local application of bFGF at the time of injury has the potential to prevent vocal fold scarring. Preventive injection of bFGF could be applied at the time of phonomicrosurgery to avoid postoperative scar formation. N/A. Laryngoscope, 2016 127:E67-E74, 2017.

Injection Laryngoplasty for The Treatment of Vocal Fold Scar, and Sulcus

Background and Objectives The clinical reports for the treatment of vocal fold scar and sulcus vocalis are limited, also there is no best one for the treatment of them. This study is to evaluate the effect of Injection laryngoplasty (IL) for the treatment of vocal fold scar and sulcus vocalis. Materials and Methods from January 2013 to May 2015, the Nineteen patients who were diagnosed as vocal fold scar, sulcus and atrophy, and underwent IL, were engaged in this study. Clinical information and voice parameters were analyzed by retrospective chart review. Pre and post voice parameters were compared. Results Subgroups of diagnosis were classified into sulcus vocalis for 12 patients, vocal fold scar for 5, and atrophy for 2. IL was performed under local anesthesia through cricothyroid membrane except one patient. Atesense®, Radiessess®, and Rofilan® were used as injected materials in 9, 9, and 1 patients respectively. Maximal phonation time (p=0.0124), dynamic range (p=0.0028), pitch range (p=0.0141), voice handicap index (p=0.028), glottal closure (p=0.0229), and mucosal wave (p=0.0132) had significant improvement for post-IL voice assessment than Pre-IL. While GRBAS, Mean flow rate, Jitter, Shimmer, Harmony to Noise ratio didn’t have improvement. Conclusion IL is a feasible option for the treatment of glottis incompetence with normally mobile vocal folds such as sulcus vocalis and vocal fold scar. Key words: Sulcus vocalis ㆍ Vocal atrophy ㆍ Scar ㆍ Injection laryngoplasty 핵심용어: 성대구증 ㆍ 성대위축 ㆍ 반흔 ㆍ 주사후두성형ìˆ

Small Intestinal Submucosa Implantation for the Possible Treatment of Vocal Fold Scar, Sulcus, and Superficial Lamina Propria Atrophy.

Evaluate the histologic effects of grafting porcine-derived small intestinal submucosa (SIS) into the vocal fold superficial lamina propria (SLP) layer for the potential treatment of vocal fold scar, sulcus and superficial lamina propria atrophy. Small intestinal submucosa was implanted into the right vocal fold SLP of 6 mongrel dogs. The left vocal fold served as a sham surgical control. At 2, 4, and 6 weeks postoperative, bilateral vocal fold specimens were evaluated histologically. At 2 and 4 weeks, respectively, SIS-implanted vocal folds demonstrated moderate and mild inflammation and acute and chronic inflammation. At 6 weeks, inflammation was minimal and chronic. The 6-week specimens showed copious amounts of newly generated hyaluronic acid (HA) within the graft. There was no reactive fibrosis at 6 weeks. In the canine model, SIS appears safe for SLP grafting. Inflammation is similar to that of sham surgery. Small intestinal submucosa results in newly generated HA without concomitant fibrosis. Small intestinal submucosa has potential to be used in treatment of disorders with SLP, including vocal fold scar, sulcus, and atrophy. Studies evaluating the effect of SIS implantation on vocal fold function, as well as the ultimate fate of the graft, are required.

The efficacy of a novel collagen-gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar.

Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen-gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α-smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose-dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm2 ; CGS + bFGF group); or a sham-treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd.