Vocal Fold Augmentation Research Articles

Triological Best Practice: Should Bedside Laryngoscopy Be Routinely Performed Following Thyroidectomy?

Triological Best Practice: Should Bedside Laryngoscopy Be Routinely Performed Following Thyroidectomy?

Vocal Fold Injection Augmentation for Post-Airway Reconstruction Dysphonia: A Case Series.

Post airway reconstruction dysphonia (PARD) is common and has a significant effect on the quality of life of patients. Vocal fold injection augmentation (VFIA) is one treatment that can be used to improve glottic insufficiency in some patients. The goal of this study was to characterize the use and outcomes of VFIA for PARD. Retrospective chart review from January 2007 to July 2018 at a tertiary pediatric care center. Consecutive patients with PARD who underwent VFIA, who had a preoperative voice evaluation and a follow-up evaluation within 3 months after VFIA (fat, carboxymethylcellulose gel, hyaluronic acid). Thirty-four patients (20 female) underwent VFIA. The mean age at the time of the injection was 13.6 years (SD 6.1). Twenty patients (58.8%) had a history of prematurity and a mean of 1.8 open airway surgeries. After injection, 29/34 patients (85.3%) noted a subjective voice improvement. The baseline Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) overall severity score decreased by a mean of 5.7 (SD = 19.6) points, P = .12. Total pediatric Voice Handicap Index (pVHI) improved by 6.0 (SD = 19.5) points, from 57.4 (SD = 20.0) to 51.4 (SD = 17.2), P = .09. Functional pVHI subscore demonstrated a significant improvement, with a decrease of 3.4 (SD = 7.3) points, P = .02. All procedures were performed as an overnight observation and no complication occurred. Patients with PARD represent a complex subset of patients. VFIA is a straightforward intervention that may improve voice perception. Many patients reported subjective improvement despite minimal objective measurement. Further work is warranted to elucidate the role of injection in management of PARD.

Inflammatory complications of vocal fold injection with hyaluronic acid: a multiinstitutional study

Background/aimThis study aimed to assess the inflammatory adverse reactions of vocal fold injection laryngoplasty with hyaluronic acid.Materials and methods This study was a retrospective chart review of patients who underwent vocal fold injection augmentation with HA injection from January 2005 to September 2016 in nine different institutions. Demographic data, indication for injection, injection techniques, types of injection material, settings of procedure, and complications were reviewed. The types of complication, onset time, and management of complications were also noted.ResultsIn all, 467 patients were identified. The majority of patients had been injected under general anesthesia (n = 382, 84.7%). For injection material, two different types of hyaluronic acid were used: hyaluronic acid alone or hyaluronic acid with dextranomer. Complications occurred in nine patients (1.9%). The majority of complications were inflammatory reactions (n = 7, 1.47%). Main symptoms were dysphonia and/or dyspnea with an onset of 0 h to 3 weeks after the hyaluronic acid injection. Three patients were hospitalized, one of which was also intubated and observed in the intensive care unit for 24 h. Systemic steroids and antibiotics were the main medical treatment in the majority of cases. There was no statistical difference in complication rates between patients who received hyaluronic acid and those who received hyaluronic acid with dextranomer (P = 0.220). ConclusionHyaluronic acid can be considered as a safe substance for the injection of vocal folds with a low risk of inflammatory reaction.

In vivo vocal fold augmentation using an injectable polyethylene glycol hydrogel based on click chemistry.

It is important to focus on urgent needs in clinics and develop optimal materials. For successful augmentation of vocal folds, the ideal filler should be injectable through a syringe, and should stably maintain its volume for a long time without toxicity. To achieve these criteria, a click chemistry-based PEG (polyethylene glycol) hydrogel was developed and applied for vocal fold augmentation in vivo. The PEG hydrogel enables fast gelation in vivo after injection and provides long-term stability. Azide- and dibenzocyclooctyne (DBCO)-modified 4-arm PEG were cross-linked by chemical conjugation via click chemistry and yielded gelation within several minutes. After subcutaneous injection into mice and rats, the PEG hydrogel showed higher stability after 1 month compared to the traditionally used calcium hydroxyapatite-carboxymethyl cellulose (CaHA-CMC) filler. In rabbit models with vocal fold paralysis, the PEG hydrogel stably fixed the paralyzed vocal fold in 4 months and minimized the glottic gap. It was an improved therapeutic result compared to CaHA-CMC, demonstrating the potential of a click chemistry-based PEG hydrogel for vocal fold therapy.

Fibrin Gel Suspended Autologous Chondrocytes as Cell-based Material for long-term Injection Laryngoplasty.

Injection laryngoplasty of materials for unilateral vocal-fold paralysis has shown various results regarding the long-term stability of the injected material. We evaluated a fibrin-gel based cell suspension with autologous chondrocytes in-vitro and in-vivo as long-term-stable vocal-fold augmentation material in an animal model. This study compises an in vitro cell-culture part as well as an in vivo animal study with New Zealand White Rabbits. In in-vitro experiments, auricular chondrocytes harvested from 24 New Zealand White Rabbits cadavers were cultivated in pellet cultures to evaluate cartilage formation for 4 weeks using long-term-stable fibrin gel as carrier. Injectability and injection volume for the laryngoplasty was determined in-vitro using harvested cadaveric larynxes. In-vivo 24 Rabbits were biopsied for elastic cartilage of the ear and autologous P1 cells were injected lateral of one vocal cord into the paraglottic space suspended in a long-term-stable fibrin gel. Histologic evaluation was performed after 2, 4, 12, and 24 weeks. During 12-week pellet culture, we found extracellular matrix formation and weight-stable cartilage of mature appearance. In-vivo, mature cartilage was found in two larynxes (n = 6) at 4 weeks, in four (n = 6) at 12 weeks, and in five (n = 6) at 24 weeks mostly located in the paraglottic space and sometimes with spurs into the vocalis muscle. Surrounding tissue was often infiltrated with inflammatory cells. Material tended to dislocate through the cricothyroid space into the extraglottic surrounding tissue. A cell-based approach with chondrocytes for permanent vocal-fold augmentation has not previously been reported. We have achieved the formation of structurally mature cartilage in the paraglottic space, but this is accompanied by difficulties with dislocated material, deformation of the augmentation, and inflammation. N/A Laryngoscope, 131:E1624-E1632, 2021.

Five-year results of vocal fold augmentation using autologous fat or calcium hydroxylapatite.

To evaluate 5-year voice outcomes of vocal fold augmentation (VFA) using autologous fat (AF) injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. Retrospective study of patients who underwent VFA between 2012 and 2015, with a 5-year follow-up. Patients with a glottic gap of ≤ 3mm caused by unilateral vocal fold paralysis or vocal fold atrophy were included in the study. VFA was performed using AF injection via direct microlaryngoscopy in 17 patients, and using office-based CaHA injection in 19 patients. Subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection, and at 12 and 60months post-VFA. Altogether 36 patients underwent VFA between 2012 and 2015, of whom 5 were excluded within 1year post-VFA, and 2 were excluded between 1 and 5years post-VFA. Of the remaining 29 patients, 3 (10.3%) underwent re-intervention at between 1 and 3years post-VFA. Thus, the 5-year follow-up included 26 patients (72.2%; 11 males and 15 females). At 5years after surgery, 73.1% of the patients were satisfied with their voice, with no significant between-group difference (P=0.307). The mean improvement of VHI was 28.8±17.82 in the autologous fat group versus 33±26.24 in the CaHA group (P=0.458). MPT improvement was also similar between the two groups: 6.2±4.26 for the autologous fat group versus 6.3±4.34 for the CaHA group (P=0.667). Both AF injection via direct microlaryngoscopy and office-based CaHA injection yielded good and comparable 5-year results.

A Very Rare Complication of Vocal Fold Augmentation With Calcium Hydroxylapatite: Neck Abscess

Vocal fold injection augmentation is performed routinely for the treatment of glottic insufficiency especially due to unilateral vocal fold paralysis. There are numerous materials that are used for injection laryngoplasty, calcium hydroxylapatite being one of them. We present an interesting case of a 64-year-old male patient with metastatic acinic cell carcinoma of the right parotid gland, who underwent right vocal cord injection laryngoplasty with calcium hydroxylapatite for right vocal cord paralysis with glottal insufficiency and developed a neck abscess. This is the first report in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. It seems that over injection of the vocal fold gave rise to extravasation of the injected material outside the laryngeal framework which later became a nidus for infection. We present the first case in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. Clinicians should be aware of this rare but dangerous complication.

Office-Based Procedure Training in Laryngology Fellowship Programs.

To assess the current practices and challenges of training office-based procedures to laryngology fellows in the United States. An anonymous web-based survey study was distributed to laryngology fellowship program directors, as listed by the American Laryngological Association. The survey was a 19-item questionnaire with free-text, Likert scale, and multiple-choice answers. Twenty-two of 27 program directors (81.4%) replied to the survey. Many programs (8/16) have three or more laryngologists and do more than 10 procedures each week (10/16). Sixty-nine percent (11/16) of directors had not been trained for office procedures in their fellowship. The fellows are allowed to be primary surgeon on 68.75% and 75% of vocal fold augmentation and laser procedures, respectively. The expected competencies for these procedures on graduation are average-moderate and moderate. When program directors asked about the methods used for training, a minority of them use simulators (2/16), procedural checklists (2/16), or structured debriefing (2/16). The most commonly used methods were case-based troubleshooting (13/16) and unstructured debriefing (13/16). Patients being awake and patients' expectations are seen as the most important obstacles. Most of the directors thought office-based procedure training could be improved (14/16). The most common suggestions were using step-wise checklists, simulator-labs, and formal debriefings. This is the first study evaluating the training of office-based laryngeal procedures during laryngology fellowship. Given the increasing importance of these procedures in practice and the herein identified barriers and need for improvement, fellowships should investigate the use of systematic training tools to improve fellow competency with office-based procedures. Laryngoscope, 131:2054-2058, 2021.

Vocal Fold Fat Augmentation for Atrophy, Scarring, and Unilateral Paralysis: Long-term Functional Outcomes.

There is a debate regarding the durability of fat implants. Our experience and recent publications suggest fat implantation may deliver a long-lasting improvement. This study aims to present the long-term outcomes for vocal fold fat augmentation using strict harvesting, preparing, and implantation protocols. A prospective cohort conducted between 2014 and 2020 (recruitment 2014-2017). An academic tertiary referral center. Twenty-two patients with glottic insufficiency were enrolled: 11 had unilateral vocal fold paralysis (UVFP), and 11 had atrophy or scar. Harvested fat was injected unilaterally or bilaterally into multiple sites. Six of these patients also had simultaneous microlaryngoscopic removal of other benign glottic lesions. Outcome measurements included video stroboscopy; Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) score; Voice Handicap Index (VHI); and acoustic analysis, performed preoperatively, 3, 12, 24, and 36 months after surgery. Ten augmentations were unilateral and 12 bilateral. Comparing the preoperative and 36-month postoperative periods, the mean VHI score improved from 73.45 (±22.78) to 44.88 (±28.93), P = .001, and the mean GRBAS decreased from 8.64 (±3.89) to 2.82 (±2.3), P = .001; 24 months postoperatively, the mean fundamental frequency decreased from 163.88 Hz (±41.61) to 150.44 Hz (±41.47), P = .012. Stroboscopic analysis revealed statistically significant improvement in mucosal wave propagation, phase closure, and phase symmetry. Best results were achieved in the UVFP subgroup. Computed tomography scans demonstrated long-term viability of the implanted adipose tissue. Fat is an excellent source of autologous graft. With careful patient selection and proper surgical technique, fat is suitable for long-term correction of glottic insufficiency. Fat augmentation should be considered as a long-lasting or even permanent solution, rather than temporary.

The Aging Voice

Age-related dysphonia in the elderly is more common than appreciated because it is an under-reported symptom. Perceptually, the presbyphonic voice is characterized negatively as sounding weak, breathy, tremulous, and unstable. The frequent association with hearing impairment in this group may lead to social isolation and depression, with a significant impact on quality of life. Although several anatomical and physiological alterations are known to contribute to presbyphonia, singing prevents, in large part, many of the perceptual changes. Vocal exercises, with vocal fold augmentation or thyroplasty when indicated, provide significant improvement. Many older individuals with recognized clinical signs of presbylarynx, such as vocal atrophy, report a normal voice. This suggests that the mere presence of presbylarynx does not necessarily result in presbyphonia. Recognition of presbyphonia is important because of its significant impact on quality of life. Appropriate diagnosis is essential in order to provide effective therapy.

Management of postoperative dysphagia after prosthetic laryngoplasty or arytenoidectomy.

To evaluate the efficacy of various treatments for dysphagia after laryngeal surgery. Retrospective. Horses treated for dysphagia after laryngeal surgery. Medical records of horses treated for dysphagia after prosthetic laryngoplasty (PLP) or partial arytenoidectomy (PA) were reviewed. Signalment, prior surgery, preoperative videoendoscopic diagnosis, and surgical treatments were recorded. Short- and long-term follow-up were obtained. Chi-square and logistical regression were performed to correlate independent variables and outcomes. Forty-four percent of horses with prior PLP and 88% of horses with prior PA had persistent resting dorsal displacement of the soft palate (DDSP). Vocal fold augmentation (VFA) as a single treatment was most commonly performed (n = 22), followed by laryngoplasty removal (LPR; n = 1). Fifteen horses received a combination of treatments: VFA (n = 15), LPR (n = 4), laryngeal tie-forward (LTF; n = 2), and esophageal release (n = 1). Short-term clinical outcomes were reported; 80% of horses treated with VFA (n = 35) had resolution of dysphagia, and 20% were improved. Among the 33 horses available to long-term follow-up, 31 (94%) returned to some level of work, and DDSP during work was reportedly resolved in 23 of 25 horses. Vocal fold augmentation resulted in resolution of symptoms relating to dysphagia in 81% of horses. Twenty percent of horses treated with LPR had sustained resolution of dysphagia. A combination of LPR, VFA, LTF was performed in 18% of horses. Treatment options directed at altering laryngeal geometry and/or position of the larynx were successful in resolving 86% of dysphagia in horses previously regarded as very difficult to treat.

Injection Laryngoplasty for Management of Neurological Vocal Fold Immobility.

Injection laryngoplasty as used in this chapter is synonymous with the term "injection augmentation." Injection augmentation is a technique designed to enhance glottic closure in patients with glottic insufficiency, or failure of glottic closure, by injecting material into the lateral aspect of the vocal fold to move the vibrating surface to the midline. This type of injection augments the vocal fold and improves glottic closure. Injection augmentation originated over 100 years ago. However, the current indications, techniques, and materials have changed significantly. Paralysis, defined as loss of function due to neu-rological injury, remains a common cause of glottic insufficiency. In cases of paralysis, nerve function to adduct the vocal folds for voice production and coughing is interrupted, bilaterally or unilaterally, and the glottis becomes insufficient. While unilateral vocal fold paralysis remains the most common indication for vocal fold injection augmentation, due to the development of newer injectable materials and less invasive injectable techniques, surgeons routinely perform injection augmentation for glottic insufficiency due to other causes such as vocal fold paresis, vocal fold atrophy, presbylarynx, vocal fold scar, and soft tissue loss. Additionally, there is an increasing performance of vocal fold injection in the awake patient. This allows for immediate feedback and reduced anesthetic risk. Outcomes assessment for injection augmentation remains varied by lack of consensus and large-scale studies to identify the factors most instrumental in documenting optimal results. We review the history of injection laryngoplasty, the indications for injection, choice of injectate, outcomes, complications, and future directions of injection laryngoplasty for augmentation.

Autologous Fat Augmentation in The Treatment of Unilateral Vocal Fold Paralysis – A 15-Year Experience in a Single Institution

SUMMARYAutologous fat vocal fold augmentation is a widespread surgical procedure that aims to repair glottal incompetence in patients with unilateral vocal fold paralysis (UVFP). However, there are some concerns in the literature about the long-term results of this technique. At the ENT Department of the Zagreb University Hospital Centre, this technique has been in use for more than 15 years, and a retrospective medical chart review was conducted from June 2005 to November 2019. Overall, 78 patients with UVFP met the inclusion criteria for enrolment in the study. All patients underwent at least one preoperative and two postoperative voice assessments, one early (within 3 months from surgery) and one late (at least 1 year after surgery). All tested voice outcome parameters (maximum phonation time (MPT), jitter, shimmer, noise-to-harmonic ratio (NHR)) significantly improved after surgery, both early and late postoperatively (p<0.001). The reoperation rate was only 10.3% (8/78), with the majority of patients in our series experiencing long-term benefits from this surgical procedure. According to the results of our study, autologous fat vocal fold augmentation appears to be a highly useful and effective surgical technique with long-lasting results in the majority of patients suffering from UVFP.

Development of a microporous annealed particle hydrogel for long-term vocal fold augmentation.

The purpose of this study was to develop and provide evidence of a novel permanent injectable biomaterial for vocal fold augmentation with the potential to treat glottic incompetence by evaluating its performance in two animal models. Animal model. Microporous annealed particle (MAP) hydrogel was fabricated using a water-in-oil emulsion method and synthetically tuned to match the stiffness modulus of native vocalis muscle. Thirty-two New Zealand White rabbits were administered unilateral injections of MAP (n = 16), saline (n = 8), and the clinical standard hyaluronic acid (Restylane-L) (n = 8), and evaluated at day 0, and 6-week, 4-month, and 6-month endpoints. Induced vocal fold vibration was recorded with a high-speed camera prior to euthanization, with glottic closure and mucosal wave characteristics assessed both quantitatively and qualitatively by an experienced voice clinician. Histologic analysis was performed to assess scaffold permanence, immunogenicity, and vascularization within the scaffold. Histologic analysis confirmed the MAP gel treatment group maintained its volume without migration for 6 months postimplantation. Immune staining showed minimal to nonexistent immunogenicity over the course of the implant lifetime. Extensive tissue integration and vascularization was observed histologically within the MAP gel group by immunofluorescence staining. Mucosal wave was not impaired by any of the injected materials, including the MAP gel augmentation. MAP gel is a nonresorbable biostimulatory injectable implant that provides superior tissue integration, stiffness matching, and permanence compared to current injectable implants, with retained biomechanical function, suggesting its potential as a new therapeutic for glottic incompetence. NA Laryngoscope, 130:2432-2441, 2020.

Relationship of vocal fold atrophy to swallowing safety and cough function in Parkinson's disease.

When swallowing function is compromised in patients with Parkinson's disease (PD), cough plays a crucial role in clearing the airway and preventing pulmonary complications. The aim of this study was to determine the influence of vocal fold atrophy severity as measured by the bowing index (BI) on airway protection in PD. Thirty participants with PD completed measures of voluntary and reflex cough. Flexible laryngoscopy with endoscopic evaluation of swallowing allowed for measurement of BI using ImageJ software. Swallowing safety was scored on the Penetration-Aspiration Scale (PAS). Regression and receiver operating characteristic (ROC) analyses were performed to test our study aim. Twenty-four of 30 participants had some degree of vocal fold atrophy (BI >0). When controlling for age, disease duration did not significantly influence BI. BI was not predictive of any sensorimotor parameters of cough including measures of cough airflow, reflex cough threshold, or urge to cough. BI discriminated participants with near-normal (PAS 1-3) swallowing safety from participants with impaired (PAS 4-8) swallowing safety (P = .01, sensitivity: 87.0%, specificity: 71.4%, cutoff value BI >4.6). Vocal fold atrophy is a potential factor contributing to poor swallowing safety in PD. BI was not associated with cough function in this PD cohort, contrary to prior studies that have shown improved cough measures after vocal fold augmentation. Vocal fold atrophy in PD remains an important area of study as a targetable intervention for patients with airway protective dysfunction. Future studies should include measures of glottic closure during vocal fold adduction. Level 3 Laryngoscope, 130:303-308, 2020.

The Larynx as a Target for Treatment in Chronic Refractory Cough

Chronic cough is a common and debilitating problem that remains refractory to medical treatment. Laryngeal dysfunction frequently occurs in chronic cough. The goal of this review was to explore new developments in the mechanism treatment of chronic cough particularly those that target laryngeal function. Treatments for chronic cough that target laryngeal sensation and motor function have include speech pathology, neuromodulators, botulinum toxin, trigger reduction and vocal fold augmentation. Speech pathology treatment for chronic cough can be successful; however, the mechanism behind improvement is unknown. Emerging therapies such as botulinum toxin and vocal fold augmentation show promise and are useful treatments for cough that does not respond to medical or speech pathology management.

Management of Vocal Fold Scars by Concurrent Nanofat and Microfat Grafting.

Vocal fold scarring is the cause of severe dysphonia and represents a therapeutic challenge; dysphagia can also be present in case of soft tissue defect due to previous oncological surgery. The ideal surgical solution should concurrently provide vocal fold augmentation and re-establishment of tissue elasticity. Nanofat technique has given so far promising results in remodeling skin scars and improving tissue pliability. The present paper describes for the first time the use of nanofat injected into the vocal fold cover for pliability restoration, combined with traditional microfat for vocal fold augmentation. Seven patients (aged 23-77 years) affected by severe dysphonia, related to extensive vocal fold scarring (3 of them were also affected by dysphagia for liquid consistencies), underwent a single procedure of concurrent microfat and nanofat vocal fold injection under direct microlaryngoscopy in general anesthesia. Results were evaluated by objective outcome measures and auto evaluation performed by questionnaires concerning the phonatory and swallowing efficiency. The voice quality and the perceived swallowing capability of all patients improved after surgery and are stable at follow-up (4-8 months). The reported preliminary data show that nanofat, due to its regenerative potential related to adipose-derived stem cells and growth factors, can be a promising adjunct to traditional fat augmentation to improve elasticity of the delicate multilayered structure of the vocal fold and to enhance its vibratory capabilities. Further experience on a wider number of patients and long-term follow-up are necessary to confirm the validity of this technique.

Dysphagia in Parkinson's Disease Improves with Vocal Augmentation.

While voice-related disorders in Parkinson's disease (PD) are commonly discussed in the literature, dysphagia in PD is less widely published. Vocal fold augmentation, including injection laryngoplasty (IL), is a well-established treatment for glottal insufficiency (Cates et al. in Otolaryngol Head Neck Surg 155(3):454-457, 2016). This study aimed to observe the effects of IL in PD patients with vocal bowing, with or without therapy, on glottic closure and patient-reported dysphagia outcomes. The study design was based on retrospectively collected database and cohort-case series. PD patients selected for retrospective review over a 2-year period were referred and evaluated in the Voice, Swallowing, and Airway multidisciplinary clinic by speech language pathologist and laryngologist, and were undergoing IL. Charts were reviewed for age, gender, Body Mass Index (BMI), onset of PD, and Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS) scoring. We compared pre/postoperatively (> 1 < 3months) using validated patient-reported outcome tools: Reflux Symptom Index (RSI), Glottal Function Index (GFI), Eating Assessment Tool-10 (EAT), and stroboscopic examinations. The study included 14 patients undergoing 22 IL or 1.6 IL/patient: mean age 70years (63-80), 100% male, and BMI 25.9 ± 4.3 (mean ± SD). MDS-UPDRS scoring 33 ± 20 (moderate severity), with time between PD diagnosis and IL 8 ± 10years. All patients had pre- and post-stroboscopic examinations; however, only 4:14 underwent formal swallowing evaluation. Overall, 14 IL patients improved on patient-reported measures (ΔRSI = 4; ΔGFI = 3; ΔEAT = 4). Based on the findings of the study, we conclude that PD is a progressive neurodegenerative condition with dysphagia. The presented pilot data suggest that IL may be considered as a beneficial adjunct for PD patients with glottal insufficiency. LEVEL OF EVIDENCE: 4.

Efficacy of Calcium Hydroxyapatite in Vocal Fold Augmentation for Unilateral Vocal Fold Paralysis in Asian

Efficacy of Calcium Hydroxyapatite in Vocal Fold Augmentation for Unilateral Vocal Fold Paralysis in Asian

Dual growth factor-immobilized bioactive injection material for enhanced treatment of glottal insufficiency

With increasing demand for treatment of glottal insufficiency, several injection materials have been examined. However, biological resorption, degradation of injected materials, and the subsequent need to perform multiple injections still remain major clinical problems. In this study, we fabricated two different growth factor (GF) [single basic fibroblast growth factor (bFGF), single hepatocyte growth factor (HGF), or dual bFGF/HGF]-immobilized polycaprolactone (PCL)/Pluronic F127 microspheres. These materials were investigated for their potential use as bioactive injection laryngoplasty agents. HGF was found to be continuously released over 20 days and the bFGF was found to be continuously released over 25 days, as demonstrated by ELISA assay. Human vocal fold fibroblasts (hVFFs) showed significantly higher proliferative ability on dual GF-immobilized microspheres. GF-immobilized microspheres (bFGF, HGF, and dual GF) were injected into paralyzed vocal folds of New Zealand white rabbits. Through endoscopic observation and H&E staining, we identified that the microspheres remained localized at the injection site, resulting in constant volume augmentation of the paralyzed vocal fold without significant loss of the initial volume after 4 weeks. The expression of genes related to the extracellular matrix (ECM) in the vocal fold was upregulated by dual GF-immobilized microspheres. Furthermore, dual GF-immobilized microspheres inhibited muscle degeneration and upregulation of myogenic-related genes. In conclusion, dual GF-immobilized microspheres passively augmented the volume of the paralyzed vocal fold while actively inducing ECM synthesis at the injected vocal fold and preserving muscle tissue. Dual GF-immobilized microspheres could be a new and promising injection material for paralyzed vocal folds. Statement of SignificanceLimitation of prolonged augmentation of vocal fold and degeneration of vocal fold tissue still remain as major clinical problems in the treatment of vocal fold paralysis. Herein, we fabricated the polycaprolactone (PCL)/Pluronic F127 microspheres to augment volume of paralyzed vocal folds. On top of that, we additionally immobilized the growth factors (bFGF, HGF, or dual bFGF/HGF) on the surface of these microspheres. We highlight the efficacy of the dual GF-immobilized microspheres which augmented the volume of the paralyzed vocal fold passively, induced ECM synthesis actively at the injected vocal fold and preserved laryngeal muscle tissue. Our results suggest that the dual GF-immobilized microsphere could be a new promising injection material for injection laryngoplasty to treat paralyzed vocal fold.