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.

[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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus.

This study aimed to evaluate the potential of embryonic stem cell-derived neural progenitors for use as transplants for the replacement of the auditory primary neurons, spiral ganglion neurons. Mouse embryonic stem cell-derived neural progenitors were implanted into the base of the cochlear modiolus of normal or deafened guinea pigs, which contains spiral ganglion neurons and cochlear nerve fibers. Histological analysis demonstrated the survival and neural differentiation of transplants in the cochlear modiolus and active neurite outgrowth of transplants toward host peripheral or central auditory systems.