Treatment of aging vocal folds: novel approaches.

PURPOSE OF REVIEW: This article aims to review previous research reports and to summarize current strategies for the treatment of the aging vocal fold using regenerative medicine and tissue engineering, with a particular focus on growth factor therapy. RECENT FINDINGS: Previous studies have elucidated age-related histological and gene expression changes in key extracellular matrix components, such as collagen and hyaluronan, in the lamina propria of the aging vocal fold. On the basis of these findings, our research group has focused on growth factor therapy to restore extracellular matrix distribution in the aging vocal fold to a younger state. Results from recent studies with basic fibroblast growth factor and hepatocyte growth factor provided preliminary evidence of the regenerative effects of growth factor therapy on treatment of the aging vocal fold. In addition, a clinical trial using basic fibroblast growth factor revealed improvements of maximum phonation time, mean flow rate, and acoustic parameters in atrophied vocal folds. These positive findings suggest that the administration of basic fibroblast growth factor may become a useful tool for the treatment of the aging vocal fold. SUMMARY: Regenerative medicine and tissue engineering are innovative strategies for the treatment of aging vocal folds, and recent reports have also confirmed the therapeutic potential of growth factor therapy for the treatment of the aging vocal fold. More recently, the clinical application of basic fibroblast growth factor was reported with encouraging outcomes. Continued basic research and clinical investigations will be required to develop strategies to overcome age-related voice disorders.

[Perioperative management of thyroid surgery in patients treated with drug-eluting stents].

The use of drug-eluting stents (DES) has been spreading worldwide to treat coronary heart disease. Patients treated with DES need long-term dual antiplatelet therapy with aspirin and thienopyridine to prevent stent thrombosis. Perioperative management is important to prevent postoperative complications in thyroid surgery if thyroid surgery is considered in patients who have been treated with DES. However, no evidence exists regarding the safety of perioperative management in patients treated with DES. We reviewed two cases of patients undergoing thyroid surgery after DES implantation. In the two cases, our protocol was adopted for perioperative management, and postoperative complications were assessed. Our thyroid surgeries were performed safely and free from serious complications such as stent thrombosis and postoperative bleeding. Under our protocol, patients after DES implantation were safely treated without severe complications. We believe that our protocol for perioperative management is useful for thyroid surgery.

Topical morphine gel for pain management in head and neck cancer patients.

Pain is common in head and neck cancer patients. Regardless of the cause, pain management is essential in supportive care. Recent research has suggested that opioid receptors on peripheral nerve terminals may play an important role in pain modulation. A number of publications have reported the use of topical morphine for painful ulcers that occur because of a variety of medical conditions. To the best of our knowledge, there are no reports in the literature regarding the use of morphine gel in head and neck cancer patients. We present two cases treated with morphine gel therapy for cutaneous pain resulting from radiation-induced dermatitis and tumor infiltration. We obtained good pain control in both cases without side effects. In one case, the use of the gel allowed a decrease in systemic opioid medication, and adverse effects of systemic opioid administration were resolved. Our experience suggests that this treatment presents great potential for selected head and neck cancer patients, especially those with prominent pain limited to the body surface.

Effects of raised-intensity phonation on inflammatory mediator gene expression in normal rabbit vocal fold.

OBJECTIVE: To investigate the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory messenger RNA (mRNA) expression in vivo. STUDY DESIGN: Prospective animal study. SETTING: Laboratory. SUBJECTS AND METHODS: Ten New Zealand White breeder rabbits received 30 minutes of experimentally induced modal or raised-intensity phonation, followed by a 30-minute recovery period. A separate group of five rabbits served as sham controls. Real-time polymerase chain reaction was performed to investigate the mRNA expression of interleukin 1beta (IL-1beta), transforming growth factor beta-1 (TGFbeta1), and cyclooxygenase-2 (COX-2). Separate one-way analysis of variance (ANOVA) tests were used to investigate differences in gene expression across groups, with an appropriate alpha correction of 0.016 to control for type I error. Significant main effects were further examined using Fisher's least significant difference. RESULTS: ANOVA revealed that there were differences for IL-1beta, TGFbeta1, and COX-2 between sham control, modal phonation, and raised-intensity phonation (P 0.0001). Pairwise comparisons revealed that the expression of IL-1beta, COX-2, and TGFbeta1 increased significantly during raised-intensity phonation, compared to modal phonation and sham control (P 0.0001). CONCLUSION: Results provided support for the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory mRNA expression. Future studies will investigate the signal transduction pathways and mechanisms regulating the vocal fold inflammatory response. The long-term goal of these studies is to advance understanding of the molecular and cellular events underlying phonation-related tissue alterations.

Age-associated changes in the expression and deposition of vocal fold collagen and hyaluronan.

OBJECTIVES: We investigated age-associated changes in the expression and deposition of collagen and hyaluronan (hyaluronic acid; HA) in aged vocal folds. METHODS: Thirty Sprague-Dawley rats were involved in this study. For gene expression analyses, 15 animals were divided into 3 age groups of young (2 month), adult (9 month), and elderly (18 month) rats. Real-time polymerase chain reaction testing was used to quantify the messenger RNA expression of procollagen types I and III, matrix metalloproteinases 2 and 9, and HA synthases 1, 2, and 3. The remaining 15 animals were divided into 3 similar age groups and underwent histologic analyses designed to investigate age-associated changes in the deposition of collagen and HA. RESULTS: The results revealed down-regulated expression of procollagen types I and III, matrix metalloproteinases 2 and 9, and HA synthases 1, 2, and 3 in adult and elderly vocal folds, compared to young vocal folds. Histologically, staining of collagen was dense in the vocal folds of adult and elderly rats, and HA was less dense in the vocal folds of adult and elderly rats than in young rats. CONCLUSIONS: A slowdown in the expression of procollagens and matrix metalloproteinases was associated with dense collagen in aged vocal folds, as observed in elderly humans. A similar decrease in the expression of genes that code for HA synthase was consistent with a low density of extracellular matrix HA in the vocal folds of elderly rats.

In situ tissue engineering of canine skull with guided bone regeneration.

CONCLUSION: Calcium alginate (CA) membrane prevents excessive fibrous tissue intrusion and/or dislocation of a bone scaffold. However, CA membrane did not always accelerate cranial bone regeneration. OBJECTIVE: We previously reported skull regeneration using a bone substitute material (BSM), which consisted of collagen-coated beta-tricalcium phosphate and autologous bone fragments, and bone marrow-derived stromal cells (BSCs). However, excessive fibrous tissue intrusion or dislocation of the BSM occasionally interrupted bone regeneration. To avoid such problems, we examined CA membrane, which is useful for guided bone regeneration (GBR), to investigate whether this material maintains the bone regenerative space. MATERIALS AND METHODS: Bone defects (2x2 cm) were created in the skulls of 12 adult beagle dogs using the same clinical procedure. Four experimental models were tested with or without BSM plus BSCs or CA membrane. In group I, the original free bone flap was replaced at the defect. In group II, after replacing the bone flap, the defect was covered with CA membrane. In group III, BSM plus BSCs were used as a gap filler. In group IV, BSM plus BSCs and CA membrane were applied. Histological examinations were performed 3 and 6 months after the operation. RESULTS: In groups I and II, bone regeneration was not observed but fibrous tissue intrusion was prevented in group II. Bone neogenesis was more observed in group III than in group IV at 3 months (p<0.05). At 6 months, the regenerated areas were larger than those observed at 3 months, but the differences between groups III and IV were not statistically significant.

Regenerative effects of basic fibroblast growth factor on extracellular matrix production in aged rat vocal folds.

OBJECTIVES: We investigated acute changes in extracellular matrix (ECM) gene expression and histologic changes in the deposition of collagen and hyaluronan (hyaluronic acid; HA) after basic fibroblast growth factor (bFGF) treatment of the aged rat vocal fold. METHODS: For the polymerase chain reaction (PCR) experiments, we divided ten 18-month-old Sprague-Dawley rats into two groups that received serial injections of sham (saline solution) or bFGF (2 ng/microL) and euthanized them 2 weeks after the initial injection to investigate acute changes in ECM gene expression. We treated a separate group of 5 animals unilaterally and sacrificed them 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. RESULTS: Real-time PCR revealed significantly up-regulated HA synthase (HAS)-2, HAS-3, matrix metalloproteinase (MMP)-2, and procollagen type I gene expression in the bFGF treatment group as compared to the sham treatment group. Histologic staining revealed significantly increased deposition of HA in the bFGF-treated vocal fold as compared to the sham-treated vocal fold. No differences in ECM collagen levels were observed between treatment sides. CONCLUSIONS: Basic fibroblast growth factor induced the up-regulation of HAS-2, HAS-3, MMP-2, and procollagen type I. Histologically, aged vocal folds treated with bFGF revealed increased deposition of HA as compared to sham-treated vocal folds.

Regeneration of aged rat vocal folds using hepatocyte growth factor therapy.

OBJECTIVES/HYPOTHESIS: We investigated acute changes in extracellular matrix gene expression and histologic changes in the deposition of collagen and hyaluronan (HA) from hepatocyte growth factor (HGF) treatment of the aged rat vocal fold. We hypothesized that: 1) HGF induces matrix metalloproteinase gene expression, which might contribute to the downregulation of collagen; and 2) HGF induces hyaluronan synthase (HAS) gene expression, which might play a role in the upregulation of extracellular matrix HA. STUDY DESIGN: Prospective animal study. METHODS: Fifteen, 18-month-old, Sprague-Dawley rats were involved in this study. For gene expression analyses, 10 rats were divided into two groups and received serial injections of sham (saline) or HGF (2 ng/microL) and sacrificed 2 weeks after the initial injection to investigate acute changes in extracellular matrix gene expression. A separate group of five animals received the above treatment and were sacrificed 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. RESULTS: Real-time polymerase chain reaction revealed significantly upregulated matrix metalloproteinase(MMP)-2, -9, and HAS-3 messenger RNA (mRNA) expression and significantly downregulated procollagen type I mRNA expression in the HGF-treatment group, compared to the sham-treatment group. Histologic staining revealed significantly reduced collagen deposition and increased deposition of HA in the HGF-treated vocal fold, compared to the sham-treated vocal fold. CONCLUSIONS: HGF induced the upregulation of MMP-2, -9, and HAS-3, and downregulated the expression of procollagen type I. Histologically, aged vocal folds treated with HGF revealed decreased collagen deposition, and increased deposition of HA, compared to sham-treated vocal folds.

Characterization of raised phonation in an evoked rabbit phonation model.

OBJECTIVES/HYPOTHESIS: Our laboratory has developed an in vivo rabbit model to investigate the effects of phonation on expression and turnover of the vocal fold extracellular matrix. As a logical outgrowth of this research to include phonotrauma in the present study, we investigated the hypothesis that an increase in airflow rate delivered to the glottis produces a change in glottal configuration and an increase in mean phonation intensity. STUDY DESIGN: Prospective animal study. METHODS: Six New Zealand white breeder rabbits weighing 3 to 5 kg were used in this study. A rigid endoscope and camera were used to document glottal configuration. Acoustic signals of modal and raised phonation were recorded and digitized. Two separate one-way repeated measures analysis of variance (ANOVA) tests were used to investigate within subject differences in phonation intensity and fundamental frequency between modal and raised phonation. RESULTS: Phonation intensity was 54.19 dB SPL (6.21 standard deviations [SD]) during modal phonation, and 60.31 dB SPL (5.68 SD) during raised phonation. Endoscopic images revealed a convergent glottis, with greater separation of the vocal folds during raised phonation. Results of ANOVA revealed a significant within subjects effect for phonation intensity (P = .011). Pairwise comparisons revealed that phonation intensity increased significantly during raised phonation, compared to modal phonation (P = .008). No differences in mean fundamental frequency were observed between phonation conditions. CONCLUSIONS: Improved understanding of factors that control phonation output in the in vivo rabbit model will result in improved capabilities to match phonation dose across animals and provide immediate direction to future biochemical studies.

Extracellular matrix gene expression during wound healing of the injured rat vocal fold.

OBJECTIVES: To measure the expression of procollagen-I and -III, decorin, and hyaluronan synthase (HAS)-1, -2, and -3 during the inflammatory, proliferative, and remodeling phases of rat vocal fold injury. STUDY DESIGN: Prospective, animal model. SUBJECTS AND METHODS: Vocal folds were injured in 30 rats. Injured specimens were harvested on postinjury days 1, 3, 7, 14, 28, and 56. Five uninjured rats were used for polymerase chain reaction (PCR) control. Real-time PCR was used to measure the expression of procollagen-I and -III, decorin, and hyaluronan synthase (HAS)-1, -2, and -3. RESULTS: Compared with control, expression of procollagen-I and -III were significantly decreased on postinjury days 1 and 56; decorin expression was significantly decreased on postinjury days 1, 3, 7, and 56; HAS-1 expression was significantly decreased on postinjury days 3, 7, 14, 28, and 56; HAS-2 expression was significantly decreased on postinjury days 28 and 56; HAS-3 expression was significantly decreased on postinjury day 56. CONCLUSIONS: Results revealed time-dependent alterations in the expression of genes coding procollagen-I and -III, decorin, and HAS-1, -2, and -3. Knowledge of the temporal regulation of these genes and underlying histology will be used in future studies to investigate molecular approaches for manipulation of vocal fold injury.

Gene expression of transforming growth factor-beta1 and hepatocyte growth factor during wound healing of injured rat vocal fold.

OBJECTIVES/HYPOTHESIS: To investigate the expression of genes coding transforming growth factor (TGF)-beta1, hepatocyte growth factor (HGF), and c-Met, its membrane-spanning tyrosine kinase receptor, during the inflammatory, proliferative, and remodeling phases of wound healing in the injured rat vocal fold. STUDY DESIGN: Prospective animal study. METHODS: Thirty five rats were involved in this study. Bilateral vocal fold wounds were created in 30 rats. Injured vocal fold specimens were harvested on postinjury day 1, 3, 7, 14, 28, and 56. Real-time polymerase chain reaction (PCR) was used to quantify mRNA expression of TGF-beta1, HGF, and c-Met. Five uninjured rats were used to establish PCR control. RESULTS: Results of analysis of variance revealed a significant main effect for TGF-beta1 (P = .000), HGF (P = .000), and c-Met (P = .000) expression across time points. Post-hoc testing revealed that TGF-beta1 expression increased significantly on postinjury day 7 (P = .001) compared to control. HGF expression decreased significantly on postinjury day 1 (P = .001), and increased significantly on postinjury day 14 (P = .000). c-Met expression decreased significantly on postinjury day 1 (P = .000), day 3 (P = .000), and day 56 (P = .000), and increased significantly on postinjury day 28 (P = .000). CONCLUSIONS: Results revealed time-dependent changes in the regulation of genes coding TGF-beta1, HGF, and c-Met during wound healing in the injured rat vocal fold. These patterns of gene expression correspond well with previously reported histologic changes of the rat vocal fold after injury.

Model of evoked rabbit phonation.

OBJECTIVES: We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis. METHODS: Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube. RESULTS: Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level. CONCLUSIONS: Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.

Histologic characterization of human scarred vocal folds.

Vocal fold scarring remains a significant problem. Although several animal models have been developed to improve our understanding of the histopathology, the histologic features of scarred human vocal folds have rarely been reported. The present case studies aimed to define the histologic changes of scarred human vocal folds caused by cordectomy or cordotomy. Ten patients with the scarred vocal folds were involved in this study. Nine patients with early glottic cancer underwent endoscopic cordectomy, and one patient underwent superficial cordotomy for idiopathic scar. The postcordectomy or cordotomy scar was biopsied or resected 3-13 months after the original procedure. After confirming absence of any tumor in cancer patients, the remaining specimens were used in the present study. Histologic examination investigated deposition of extracellular matrix (ECM) including collagen, elastin, hyaluronic acid (HA), fibronectin, and decorin in the lamina propria of the scarred vocal folds. There was a wide range of variation in the deposition of ECM in scarred vocal folds. Excessive and disorganized collagen deposition was observed in most cases that had undergone deep resection of the lamina propria, whereas deposition of collagen was mild and well organized after superficial resection. Decorin was retained in all cases after superficial cordectomy or cordotomy, but varied after deep resection. Deposition of elastin, HA, and fibronectin varied regardless of depth of injury. Histology of scarred vocal folds may vary with degree of injury and individual healing mechanism.

Effect of hepatocyte growth factor on gene expression of extracellular matrix during wound healing of the injured rat vocal fold.

OBJECTIVES: We performed a prospective, sham-controlled animal study to investigate the effects of hepatocyte growth factor (HGF) manipulation of the extracellular matrix on vocal fold gene expression during acute injury. METHODS: Bilateral vocal fold wounds were created in 40 rats. The rats were randomly assigned to 1 of 2 groups (sham treatment or HGF treatment) and received treatment of the injured area at the time of wounding and on alternate posttreatment days. The injured vocal fold specimens were harvested on post-treatment days 1, 3, 7, and 14. We used real-time reverse transcription polymerase chain reaction to quantify messenger RNA expression of transforming growth factor (TGF)-beta1, procollagen types I and III, hyaluronan synthase (HAS)-1, HAS-2, and HAS-3. RESULTS: A multivariate analysis of variance revealed a significant interaction between treatment group and post-treatment day for TGF-beta1, procollagen type I, procollagen type III, and HAS-2. Post hoc testing revealed significantly lower expression of procollagen type III and significantly higher expression of HAS-2 on post-treatment day 14 in the HGF treatment group than in the sham treatment group. CONCLUSIONS: Results provide evidence of HGF treatment effects on procollagen type III and HAS-2 gene expression pathways.

Extracellular matrix gene expression after vocal fold injury in a rabbit model.

OBJECTIVES: We determined the expression of matrix metalloproteinase (MMP)-1, MMP-9, collagen types I and III, and fibronectin from rabbit vocal folds after injury. METHODS: Thirty rabbits were involved in this study. Five animals were assigned to each time period. Noninjured vocal fold specimens were collected as a control. Gene expression was analyzed at 2, 4, 8, 24, 48, and 72 hours after injury by use of real-time polymerase chain reaction. RESULTS: Compared to 2 hours after injury, MMP-1 expression was increased at 4, 8, 24, 48, and 72 hours. Compared to 4 hours, MMP-1 expression was increased at 8, 24, 48, and 72 hours. Compared to the control specimens, MMP-9 expression was increased at 4, 8, 24, 48, and 72 hours. Compared to 2 hours, MMP-9 expression was increased at 4, 8, 24, 48, and 72 hours. Compared to 2 and 4 hours, collagen type I expression was increased at 72 hours. Collagen type III expression was increased at 72 hours compared to 2, 4, and 8 hours. Compared to 2 hours, fibronectin expression was increased at 24, 48, and 72 hours. CONCLUSIONS: Results revealed time-dependent changes in expression of MMP-1, MMP-9, collagen types I and III, and fibronectin from rabbit vocal folds after injury. Future experiments are planned to investigate the effects of phonation on expression of these genes after injury.

Phonomicrosurgery for posterior glottic lesions using triangular laryngoscope.

It is important to fully expose the posterior glottis to achieve adequate phonomicrosurgical resection of lesions in the posterior glottis. However, it is often difficult to obtain a sufficient view of the posterior glottis by ordinary direct laryngoscopy. We attempted to expose posterior glottic lesions using a triangular laryngoscope for adequate achievement of the surgery. We have performed phonomicrosurgery for 14 lesions in the posterior glottis including 5 early cancers, 1 dysplasia, 1 hemangioma, and 7 granulomatous lesions. Under general anesthesia, a triangular laryngoscope was set lateral to an intubation tube, shifting the tube anterolaterally toward the opposite side to expose the posterior glottis, which allowed simultaneous visualization of the vocal fold, the lateral wall, and a part of the posterior wall of the posterior glottis. The procedures were completed successfully in all cases. Modified placement of the triangular laryngoscope provided an excellent surgical view including the membranous portion of the vocal fold through the posterior glottis. All lesions have been well controlled during the follow up periods of 6-23 months. The triangular laryngoscope enables an alternative method for posterior glottic exposure. Modified placement of the laryngoscope can be easily performed and provides sufficient exposure of posterior glottic lesions for an adequate resection of those lesions.

Expression of extracellular matrix proteins in the vocal folds and bone marrow derived stromal cells of rats.

Vocal fold scarring remains a therapeutic challenge. Our research group has indicated that bone marrow-derived stromal cells (BSCs) may have therapeutic potential in restoration of injured vocal folds. However, it is still unclear how BSCs restore the viscoelasticity of vocal fold mucosa. Since a feature of vocal fold scarring is the disorganization of the extracellular matrix (ECM), it is important to understand how BSCs produce ECM. The present study aimed to clarify ECM gene expression in BSCs, and also examined the effects of hepatocyte growth factor (HGF) on this expression. BSCs obtained from the femurs of four Sprague-Dawley rats were cultured with or without HGF. The mRNA expression of ECM components (type I procollagen, decorin, Has2, CD44, MMP-1, and GAPDH) were examined in cultured BSCs and the vocal fold mucosa by the reverse transcription-polymerase chain reaction (RT-PCR). The mRNA expression of Has2 and MMP-1 was significantly stronger in BSCs than in the vocal folds (P < 0.05). Expression of Has2 in BSCs was significantly increased by the administration of HGF (P < 0.05). There was no significant difference in the gene expression of other ECM molecules between BSCs and vocal fold mucosa. Increased expression of Has2 and MMP-1 genes from BSCs may have a positive potential in the treatment of vocal fold scarring.

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

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

The potential use of bone marrow stromal cells for cochlear cell therapy.

This study investigated the potential of bone-marrow stromal cell transplantation for cell replacement therapy in the cochlea. Bone-marrow stromal cells labeled with enhanced green fluorescent protein were injected into the perilymphatic space of normal cochleae in mice. Histological analysis 2 weeks after transplantation demonstrated that transplanted cells settled within the cochlear tissues, especially in the spiral ligament and the spiral limbus, although most transplants were located in the perilymphatic space. Some of the transplanted cells expressed the cochlear gap-junction protein connexin 26. These findings indicate the potential of bone-marrow stromal cells for delivering therapeutic molecules and for the restoration of cochlear cells, particularly in the spiral ligament and the spiral limbus.

A case of cochlear implant with internal mechanical failure.

Cochlear implantation has been performed since the 1970s and has been proven to be an effective treatment for profoundly deaf people. In some cases re-implantation has also been reported due to trauma causing implant damage, mechanical failure, extrusion, and wound infections, or device upgrade. We present a case of a 9-year-old boy with a cochlear implant in which mechanical failure occurred after a blow to his temporal region. The clinical presentation and radiographic imaging findings suggested that the cause of mechanical failure was internal failure. We performed cochlear re-implantation to the same ear and it worked well. The explanted device analysis by the manufacturer concluded that the device had failed due to a cracked hybrid integrated circuit.