Vocal Fold Augmentation Research Articles

Voice: From Cells to Song

Program Description: This miniseminar will feature thought provoking perspectives from leaders in translational and clinical research. An exploration of the pathophysiology of vocal fold scar and present cell biology treatment methods will be presented. This will include recent advances for vocal fold lamina propria rehabilitation. A discussion will be presented regarding evidence for vocal fold paralysis treatment of laryngeal framework surgery versus laryngeal re-innervation. This discussion will highlight the areas of indications and results. Advanced voice procedures to optimize voice outcomes will be presented, including laser application for a variety of voice disorders and vocal fold augmentation approaches and materials. Educational Objectives: 1) Describe the cellular biology of vocal fold scar and approaches of regenerative medicine as treatment options. 2) Interpret the known and unknown aspects of vocal fold paralysis treatment with laryngeal framework surgery in contrast to laryngeal re-innervation. 3) Apply the most modern, advanced voice surgical methods, including laser and vocal fold injection approaches.

Serial computed tomographic and positron emission tomographic properties of injection material used for vocal fold augmentation

This study aimed to demonstrate the radiological properties of hyaluronic acid (HA) and calcium hydroxylapatite (CAHA) on serial computed tomography (CT) and positron emission tomography (PET) scan. Retrospective Case Series. Retrospective chart and imaging analysis of patients who underwent HA or CAHA injection laryngoplasty. Total of 243 patients who underwent more than one CT of PET after last injection laryngoplasty were included. Sixty-eight patients received HA injection and 175 patients received CAHA injection. In all cases HA showed hypo-density in CT and no abnormal uptake on PET. CAHA showed bright calcific density on CT scan and high uptake on PET but had disappeared with time in 18 months if injected less than 0.85 mL in amount. These findings support previous clinical studies on CAHA longevity and provide proper radiological interpretation on injection materials in the vocal folds. IV (Case series).

Optimal Management of Acute Recurrent Laryngeal Nerve Injury During Thyroidectomy

Recurrent laryngeal nerve (RLN) injury is commonly encountered by thyroid surgeons and may carry with it great morbidity. Whether the injury is accidental or due to deliberate resection for oncologic soundness, the surgeon must be prepared to offer the best available treatment to patients, either at the time of injury or early in the recovery process. We review advances in treatment that allow optimal management of an acute RLN injury: ansa cervicalis–RLN reinnervation, in-office unsedated vocal fold injection augmentation, and electromyographic prognostication. The benefits and advantages of each procedure as well as relevant anatomy and techniques are delineated.

Polycaprolactone spheres and theromosensitive pluronic F127 hydrogel for vocal fold augmentation: In vivo animal study for the treatment of unilateral vocal fold palsy

The purpose of this study was to explore a novel strategy to restore vocal gap by using polycaprolactone (PCL) spheres with thermosensitive Pluronic F127 in a paralyzed rabbit vocal fold. In vivo study using a rabbit model. The PCL spheres were fabricated by an isolated particle-melting method. The PCL spheres/Pluronic F127 gel mixture was prepared by a simple mixture of PCL and Pluronic F127 solution. We used 33 New Zealand white rabbits, which were divided into normal (n = 3), vocal fold palsy (VFP, n = 12), PCL/Pluronic F127 gel mixture (PCL, n = 12), and Radiesse (n = 6) groups. After unilateral recurrent laryngeal nerve section, PCL or Radiesse were injected into paralyzed vocal folds. Laryngoscopic exams were performed 1, 2, 4, and 12 weeks after implantation; then larynx specimens were sampled. High-speed camera recording of vocal fold vibration and evaluation by videokymography were performed. Open quotient and asymmetric index were calculated. We evaluated the volume of the implants over time and investigated histologic changes. Endoscopic analysis showed that PCL/Pluronic F127 gel mixture maintained its volume without migration or inflammatory response. Vocal fold gap decreased and asymmetric vocal fold movement was improved compared with the VFP group. Histologically, connective tissue growth was observed between the spheres. The remaining volume of injected material was greater than the Radiesse group, without statistical significance. Locally injected PCL/Pluronic F127 can enhance glottal contact, suggesting it as a potential new therapeutic approach that may lead to better treatment of vocal fold palsy.

Techniques in Vocal Fold Augmentation with Autologous Fat

Techniques in Vocal Fold Augmentation with Autologous Fat

A proposal to extend application of laryngeal electromyography (LEMG)-guided vocal fold injection to treatment of unilateral vocal fold paralysis to enhance clinical popularity of LEMG: response to the paper by G.F. Volk et al.

As faithful readers of the European Archives of Otorhinolaryngology, we read with great interest the article entitled ‘‘Laryngeal electromyography: a proposal for guidelines of the European Laryngological Society’’ by Volk et al. [1]. We would like to compliment the authors and the members of the European Laryngological Society for proposing practical guidelines for laryngeal electromyography (LEMG). The equipment, monitoring, documentation, and interpretation of LEMG for vocal fold immobility were comprehensively reviewed in this paper and we believe this article will be an important reference for both beginners and experts. However, as the authors mentioned, many laryngologists do not routinely use LEMG even though it has been considered as a valuable diagnostic tool for more than 60 years. It is clear that further discussion and innovations will be needed to enhance the clinical popularity of LEMG. Here, we would like to share our ideas about using LEMG-guided vocal fold injection for unilateral vocal fold paralysis (VFP) and also propose this procedure as an innovative implementation of LEMG. According to the review by Sataloff et al. [2], LEMG has been used for diagnosis, prognosis, and treatment of laryngeal movement disorders. The two most common movement disorders in which LEMG can be applied are VFP and spasmodic dysphonia (SD). However, in their review, the authors revealed that LEMG has been used to treat SD but not VFP. Since Ludlow et al. [3] successfully used LEMG to guide botulinum toxin injection for adductor SD, injecting botulinum toxin through the cricothyroid membrane submucosally at the thyroarytenoid muscle using LEMG guidance has become the most popular treatment modality for SD [4]. Conversely, although the TA muscle is also the target of vocal fold injection augmentation for unilateral VFP, no LEMG-guided injection augmentation has ever been reported. In our experience, the accuracy of LEMG in predicting the prognosis of unilateral VFP was as high as 87 % [5]. But regardless of the result of an LEMG test, patients still need treatment for their symptoms. If we could perform vocal fold injection augmentation via an injectable needle electrode during LEMG, prognosis, evaluation, and treatment could be achieved in one step (Figs. 1, 2, video). Therefore, we propose an algorithm for adopting this Electronic supplementary material The online version of this article (doi:10.1007/s00405-012-2211-4) contains supplementary material, which is available to authorized users.

Rayleigh wave propagation method for the characterization of viscoelastic properties of biomaterials

The frequency-dependent viscoelastic properties of injectable biomaterials used for vocal fold augmentation and repair must be characterized to ensure the integrity with the vibrating tissue throughout the frequency range of vocalization. Experimental methods for quantifying the frequency-dependent viscoelastic properties of biomaterials over a broad frequency range (i.e., up to 4 kHz) using Rayleigh wave propagations were investigated. Appropriate models for Rayleigh wave propagations in single and layered media were developed. Different silicone rubber samples were made and tested to evaluate the proposed methods. Rayleigh waves at different frequencies were launched on the surface of different samples; i.e., single layer samples and samples composed of a substrate with known material properties coated with a thin layer of the soft material that is to be characterized. The input vibrations of the actuator and the motion of the sample surface were measured using an accelerometer and a laser Doppler vibrometer, respectively. A transfer function method was used to obtain the complex Rayleigh wavenumbers. Finally, the complex shear and elastic moduli and the loss factor of samples were calculated through the proper modelling using the measured wavenumbers. The results were compared and shown to be in good agreement with those obtained from other measurement methods.

Office‐Based Injection Laryngoplasty with Hyaluronic Acid Gel

Objective: Many injectables are available for vocal fold augmentation, but the role of Juvederm Ultra Plus hyaluronic acid gel has not been well examined. This study was conducted to assess the safety and clinical effectiveness of office-based injection laryngoplasty of Juvederm Ultra Plus gel in patients with glottic insufficiency (GI). Method: Prospective case series of 27 patients with GI treated with unsedated office-based injection laryngoplasty of Juvederm Ultra Plus gel over a 20 month period. Preinjection acoustic and aerodynamic measures, Voice Handicap Index, Glottal Function Index, and Dysphonia Severity Index were compared with values recorded at 1 and 4 months postinjection. Results: Data for 26 patients were available for follow-up analysis at 1 month, and 12 patients’ data were available at 4 months. Etiologies of GI included presbylaryngis (n = 11), unilateral vocal fold paralysis (n = 10), scar (n = 2), and others (n = 5). Eighty-nine percent underwent transoral injection, and 11% received transcervical injections. Significant improvements compared to preinjection levels ( P < .03) were shown in all outcome measures at 1 and 4 months, respectively. Although there were no procedural complications, 1 patient required intravenous steroid therapy for temporary glottic inflammation that resolved without permanent sequelae. Conclusion: The injection of Juvederm Ultra Plus gel is a safe procedure that allows for reliable improvements in objective and subjective outcome measures of vocal function in patients with GI provided the surgeon remains alert for the possibility of postprocedural injection site inflammation.

Transplantation of autologous chondrocytes seeded on a fibrin/hyaluronic acid composite gel into vocal fold in rabbits: Preliminary results

Injection laryngoplasty is an option for treatment of glottic insufficiency following vocal fold paralysis, vocal fold atrophy or scarring. We intended to evaluate the plausibility of autologous chondrocytes cultured with fibrin/hyaluronic acid (HA) for permanent vocal fold augmentation. Chondrocytes from rabbit auricular cartilage were expanded and cultured with fibrin/HA composite gel. 0.1 mL dosages of fibrin/HA gel with autologous chondrocytes were injected into the left vocal folds of six rabbits. Four months postoperatively, the site was evaluated endoscopically, histologically, and radiologically. None of the six rabbits showed signs of respiratory distress. Computed tomography images and endoscopic evaluation revealed sufficient augmentation volume of the injected vocal fold. Histologic data showed that the injected material did not migrate from their original insertion site. Even though the number of chondrocyte that settled down and survived in the injected site was varying in rabbits, chondrocytes successfully formed neo-cartilage at four months postoperatively in all cases. Histologically, the grafts showed no signs of inflammatory reaction and were covered with ciliated epithelium. The chondrocytes cultured with fibrin/HA could be a plausible injection material for vocal fold augmentation.

Laryngoplasty With Hyaluronic Acid in Patients With Unilateral Vocal Fold Paralysis

Augmentation of vocal fold with hyaluronic acid (Restylane; Q-Med AB, Uppsala, Sweden) is used as a therapeutic option for insufficient glottic closure in unilateral vocal fold paralysis (UVP). Analysis of the optimal glottic width, effectiveness (long-term voice improvement as a consequence of longevity of Restylane), and safety of this new method was made. In a prospective clinical cohort study, 19 consecutive patients with UVP who received vocal fold augmentation with hyaluronic acid (Restylane) were examined preoperatively; 6 weeks, 6, and 12 months postoperatively by laryngostroboscopy; and their voice was evaluated by subjective, objective, and self-assessment (Voice Handicap Index). In 11 of 19 (58%) patients, a subjectively and objectively acceptable voice quality was observed in a follow-up of 12 months. Eight of 19 (42%) patients had a considerable impairment of the voice after 6 weeks (range: 1-24 weeks). Therefore, another intervention (eg, injection laryngoplasty or thyroplasty) was recommended. An impairment of voice was mainly observed if the preoperative glottal gap during phonation was more than 1 mm. A long duration (up to 12 months) of acceptable quality of voice was achieved by augmentation with Restylane, if the glottal gap was 1 mm or less videolaryngostroboscopically during phonation. The authors recommend this therapy for temporary voice improvement and to augment vocal therapy, if spontaneous recovery of voice is likely. Long-term results remain to be seen.

Preliminary Report of Vocal Fold Augmentation with Cross‐Linked Porcine Collagen

To evaluate the short-term outcomes of using cross-linked porcine collagen for vocal fold augmentation. Case series with planned data collection. Tertiary referral hospital. Twenty consecutive patients of unilateral vocal fold paralysis (UVFP) were recruited, including 10 males and 10 females. All the subjects received videolaryngostroboscopic (VLS) evaluation for the glottic closure pattern, perceptual grading using the GRB scale (grade, roughness, breathiness), acoustic analysis, maximal phonation time (MPT), and Voice Handicap Index (VHI) questionnaire. Purified telopeptide-free, glutaraldehyde cross-linked porcine collagen was injected under local anesthesia with fiberscopic guidance. Treatment outcomes were evaluated 3 months after the injection. Fifteen (75%) of 20 patients reported complete resolution of symptoms, whereas the other 5 (25%) patients had substantial improvements. The median score of perceptual analysis of voice quality showed significant improvements from G2/R2/B2 to G1/R1/B0 (P < .001). Glottic closure pattern under stroboscopy had improved from "predominantly open" before the procedure to a "half-open and half-close" pattern after the procedure (P < .001). Acoustic analysis demonstrated significant improvements of jitter and normalized noise energy (P < .05). Maximal phonation time revealed a significant improvement from 7.5 ± 3.2 seconds to 13.1 ± 3.9 seconds (P < .01). The VHI had also decreased from 53 ± 25 points to 27 ± 20 points (P < .01). No patients had serious adverse events during the follow-up period. This case series demonstrated that porcine collagen may be a suitable material for temporary vocal fold augmentation.

Augmentation of Vocal Fold Using a Fat Block Implant Following Cordotomy Through a Minithyrotomy Approach in a Rabbit Model

Minithyrotomy is a novel approach that provides direct access to the lamina propria and vocalis muscle without requiring incision of the vocal fold mucosa. The aim of this study was to demonstrate the efficacy of minithyrotomy vocal fold augmentation in a rabbit model by comparing the vocal fold total square amount and the density of scars between the cordotomy with minithyrotomy group and a cordotomy without minithyrotomy group. Animal study. Twenty adult laboratory-conditioned female rabbits were used for this study. Minithyrotomy vocal fold augmentation was performed using a single fat block implant 3 months after cordotomy. To compare total square amount and density of vocal folds between the minithyrotomy and cordotomy group, hematoxylin and eosin, Masson's trichrome, and alcian blue staining was used. Histological examinations showed that minithyrotomy vocal fold augmentation postoperatively restored vocal fold bulkiness and maintained volume for up to 6 months, compared with the cordotomy group (P<0.05). In light of the surgical manipulation, the procedure also did not aggravate scarring of the cordectomized vocal fold. Minithyrotomy vocal fold augmentation using an autologous fat block may soon be feasible in humans undergoing rehabilitation for postcordotomy dysphonia without causing additional damage to the vocal folds.

Chondrocytes suspended in modified fibrin glue for vocal fold augmentation: An in vitro study in a porcine larynx model

Injection laryngoplasty is an option for treatment of dysphonia following vocal fold paralysis. Modified fibrin glue with suspended chondrocytes might be a favorable cell-based material for permanent vocal fold medialization. We compared fibrin glue with suspended chondrocytes to collagen and hyaluronic acid gels concerning alteration of vocal fold vibration and correct intralaryngeal placement after intralaryngeal injection into porcine larynges. Viscoelastic properties of the materials were analyzed by means of a parallel plate rheometer. Fibrin glue with cells was comparable to collagen and hyaluronic acid with respect to amplitudes, symmetry, and periodicity of vocal fold vibration. Application and positioning of fibrin glue with suspended chondrocytes were technically undemanding and comparable with controls. Complex stress modulus of fibrin glue with suspended cells was comparable to that of collagen gel. Fibrin glue with suspended chondrocytes seems suitable for the indication of injection laryngoplasty and holds promise for permanent vocal fold medialization.

Long‐term results of calcium hydroxylapatite for vocal fold augmentation

Studies have shown excellent results for 12-month post-injection augmentation data for calcium hydroxylapatite (CaHA) for glottal incompetence; however, the longevity of the material past one year was unknown. Our objective was to report the long-term effectiveness of CaHA as a vocal fold injectable by assessing data from a cohort of patients who underwent injection for glottal insufficiency. Retrospective chart review. Patients who underwent CaHA injection for glottal insufficiency of any etiology were considered for inclusion in the study. The change in Voice Handicap Index (VHI)-10 scores between preinjection scores and best postinjection scores as well as between the preinjection and the most recent VHI-10 scores were used as primary outcome measures to determine the persistence of benefit or the time to loss of benefit. Complications among the cohort were identified. Ninety patients who underwent 108 vocal fold injections with CaHA were evaluated for inclusion. Twenty patients with 22 injections met the criteria for inclusion. Fourteen of 22 (64%) subjects showed loss of benefit of the CaHA material. The average length of benefit was 18.6 months, with a range of 8 to 36 months. Three complications were identified among the original cohort of 108 injections. CaHA remains a safe and effective long-term vocal fold injectable with an average length of benefit of 18.6 months. Three complications were seen among 108 CaHA injections. CaHA is a long-term injectable with an excellent track record that does not appear to warrant concern for permanent or late complications.

Results of Acellular Dermal Graft (Surederm®) Implantation Laryngoplasty in Adhesive True Vocal Cord

Received June 1, 2011 Revised July 12, 2011 Accepted July 18, 2011 Address for correspondence Cheol Min Ahn, MD Prana Voice Clinic of Otorhinolaryngology Department Speech Clinical Laboratory, 1676-1 Seocho 1-dong, Seocho-gu, Seoul 137-881, Korea Tel +82-2-525-1713 Fax +82-2-525-1714 E-mail voiceacm@naver.com Background and ObjectivesZZThis study investigated the quality of life improvement after Surederm implantation laryngoplasty in patients with adhesive true vocal cord. Subjects and MethodZZA prospective study was conducted in 18 patients with adhesive vocal cord who underwent laryngoplasty using Surederm. The exploration of adhesive lesions or lamina propria through the fenestration allowed for the creation of a pocket for Surederm implantation within the intermediate layer of the lamina propria. Analyzed were the preoperative and postoperative parameters including the Korean-Voice Handicap Index, jitter, shimmer, noise to harmonic ratio, maximum phonation time and mucosal waves in stroboscopic findings. ResultsZZDuring the follow-up time of 12 months, the patients demonstrated excellent longterm vocal fold augmentation and significant improvement in all parameters measured. There is improved pliability of the vocal fold with good oscillation in all patients. ConclusionZZAccording to these results, it is suggested that Acellular Dermal Graft (Surederm) implantation laryngoplasty can be a stable and effective surgical treatment for adhesive true vocal cord. Korean J Otorhinolaryngol-Head Neck Surg 2011;54:629-33

Injection laryngoplasty with micronized dermis: A 10‐year experience with 381 injections in 344 patients

Micronized Dermis (MD) has been used for injection laryngoplasty for correction of glottic insufficiency since 2000. There is controversy whether the material is temporary or permanent. This is a retrospective review of 381 injections in 344 patients. From this review, we hope to better define the role of MD in injection laryngoplasty. Retrospective chart review from a single surgeon (2000-2010) The indications for MD were for both temporary and permanent correction of glottic insufficiency. The diagnoses were: vocal fold paralysis (n = 216), scar (n = 51), atrophy (n = 42), sulcus (n = 22), and others (n = 13). The material has the best effect when placed into the membranous vocal fold just lateral to the vocal ligament. The operative and postoperative complication was 1.05%. Twenty-nine percent of all injections resulted in unwanted absorption. Overinjection was needed and transcervical approach was preferred to prevent implant extrusion with overinjection. The median volume of injected material has increased from 0.8 cc to 1.0 cc over the decade. In 159 patients with long-term follow-up (>1 year), there was a 14% incidence of reinjection. Despite this, the overall need for open procedures in patients with long-term follow-up was 20%. Despite the problems of inconsistency in preparation, slow absorption and need for overinjection, micronized dermis is a safe allograft material that has long-term (>1 year) stability. The material may reduce the need for open surgery. It can be used for both temporary and permanent vocal fold augmentation.

Allograft (Alloderm) and Autograft (Temporalis Fascia) Implantation for Glottic Insufficiency: A Novel Approach

Traditionally, glottic insufficiency because of scar, atrophy, and sulcus has been treated by injection or medialization laryngoplasty. These procedures do not reestablish the vertical height of the vocal fold margin. We propose soft tissue augmentation laryngoplasty with allograft (sheet Alloderm; LifeCell Corporation, Branchburg, NJ) or autograft (temporalis fascia) via a minithyrotomy or a transoral approach. A retrospective case series analysis of 21 patients treated by sheet Alloderm or temporalis fascia for correction of glottic insufficiency. Twenty-one patients with glottic insufficiency secondary to scar, atrophy, or sulcus were treated. Ten failed prior techniques. Seventeen had minithyrotomy by a small fenestration in the thyroid cartilage. Exploration of scar or lamina propria through the fenestration allowed for the creation of a pocket for Alloderm implantation within the intermediate layer of the lamina propria. Four patients underwent a transoral approach by cordotomy with either Alloderm or temporalis fascia implantation, which also allowed for exploration of scar but required repair using sutures. These implantation approaches allowed for both restoration of the layered structure and augmentation of the middle third of the musculomembranous vocal fold. Preoperative and postoperative videostroboscopic examinations were reviewed with review of clinical outcome. With a median follow-up time of 12 months, patients demonstrated excellent long-term vocal fold augmentation and minimal absorption of the implant in 19 out of 21 patients. There is improved pliability of the vocal fold with good oscillation in scar patients. Minithyrotomy with soft tissue augmentation is a novel approach for soft tissue augmentation of glottic insufficiency. It has the advantage of augmentation of the medial edge of the vocal fold with a soft tissue implant that has long-term viability. Its role should be explored further in patients with atrophy and scar.

Three‐dimensional arytenoid movement induced by vocal fold injections

To quantitatively characterize arytenoid movement induced by vocal fold injection augmentation in an excised larynx model. : Laboratory and computational. Vocal folds of human cadaveric larynges were injected with calcium hydroxylapatite. High-resolution computed tomography scans were obtained before and after injection. Densities corresponding to the arytenoid and cricoid cartilages were extracted and processed with custom MATLAB routines to generate selective three-dimensional reconstructions of the larynx. Pre- and postinjection positions of the arytenoid were compared. Vocal fold injections resulted in predominantly small-magnitude medial rotation and medial translation of the arytenoid. Movements in other directions as would be expected in physiologic adduction were not observed. Vocal fold injection augmentation induced passive movement of the arytenoid that has not been described previously. This movement does not reproduce the trajectory of physiologic adduction. This finding has implications for the treatment of unilateral vocal fold paralysis without arytenoid repositioning maneuvers.

Comparison of fat tissues used in intracordal autologous fat injection

Conclusions: The buccal fat pad appears to be more useful as a source of fat tissues in intracordal fat injection than the abdominal fat tissues used previously. However, further studies are required to confirm this point. Objectives: Fat tissues used in vocal fold augmentation surgery have primarily been harvested from the subcutaneous region of the lower abdomen. It is often difficult to obtain sufficient fat tissue for injection due to the physical features of the individual patient. We have thus adopted a method using fat tissue from the buccal fat pad, which is already used in other plastic surgeries. Methods: This was a retrospective study. We evaluated and compared the histological characteristics of fat cells and the condition of vocal folds after injection of fat tissue extracted from the subcutaneous region of the lower abdomen and from the buccal fat pad. Results: Buccal fat cells were relatively smaller than abdominal fat cells and were not influenced by body mass index (BMI), showing less individual differences according to the physical features of the patient. Numbers of vascular endothelial cells tended to be higher in buccal fat tissues. The percentage of cases showing continuous effects for more than 6 months was slightly higher in cases using buccal fat.

Three-Dimensional Hydrogel Model Using Adipose-Derived Stem Cells for Vocal Fold Augmentation

Adipose-derived stem cells (ASCs) may provide a clinical option for rebuilding damaged superficial lamina propria of the vocal fold. We investigated the effects of five hydrogels (hyaluronic acid [HA], collagen, fibrin, and cogels of fibrin-collagen and fibrin-HA) on the differentiation of ASCs, with the long-term goal of establishing the conditions necessary for controlling the differentiation of ASC into the functional equivalent of superficial lamina propria fibroblasts. Human ASCs were isolated and characterized by fluorescence-activated cell sorting and real-time polymerase chain reaction. According to fluorescence-activated cell sorting and gene analysis, over 90% of isolated ASCs expressed adult stem cell surface markers and expressed adult stem cell genes. Scaffold-specific gene expression and morphology were assessed by culturing the ASCs in three-dimensional hydrogels. Twofold higher amounts of total DNA were detected in fibrin and cogel cultures than in collagen and HA cultures. Elastin expression was significantly higher in cells grown in fibrin-based gels than in cells grown in other gels. Cells grown in the cogels showed elongated morphology, expressed decorin marker, and exhibited glycosaminoglycan synthesis, which indicate ASC differentiation. Our data suggest that it may be possible to control the differentiation of ASCs using scaffolds appropriate for vocal fold tissue engineering applications. In particular, cogels of HA or collagen with fibrin enhanced proliferation, differentiation, and elastin expression.