Hintze, Justin

The lamina propria within the vocal fold (VF) is a complex multi-layered tissue that increases in stiffness from the superficial to deep layer, where this characteristic is crucial for VF sound production. Tissue engineered scaffolds designed for VF repair must mimic the biophysical nature of the native vocal fold and promote cell viability, cell spreading, and vibration with air flow. In this study, we present a unique tri-layered, partially-degradable hydrogel scaffold that mimics the multi-layered structure of the VF lamina propria. Using thiol-norbornene photochemistry, tri-layered hydrogel scaffolds were fabricated via layer-by-layer stacking with increasing polymer concentration from the top to middle to deep layer. Mechanical analysis confirmed hydrogel modulus increased with increasing polymer concentration. Partially-degradable hydrogels promoted high cell viability and cell spreading in 3D as assessed via live/dead and cytoskeleton staining, respectively. Importantly, partially-degradable hydrogels maintained some degree of the 3D polymer network following protease exposure, while still enabling encapsulated cells to remodel their local environment via protease secretion. Finally, the tri-layered hydrogel scaffold successfully vibrated and produced sound in proof-of-concept air flow studies. This work represents a critical first step towards the design of a multi-layered, hydrogel scaffold for vocal fold tissue engineering.

ObjectiveThe study aims to demonstrate the reproducibility and feasibility of creating a hemilaryngeal model with a medialized vocal fold (VF) using 3‐dimensional (3D) modeling techniques in both healthy larynges and those affected by cancer.Study DesignThree‐dimensional modeling of human larynges.SettingTertiary academic referral center and regenerative medicine laboratory.Subjects and MethodsComputed tomography (CT) scans from 10 healthy control and 10 patients with laryngeal cancer were segmented and imported into 3D modeling software. The larynx was cut sagittally to create a hemilaryngeal model and the vocal fold medialized. Measurements were taken from the CT and 3D model data and compared.ResultsAll control modeling data closely matched the CT data and were not statistically different from each other. There was a significant correlation between subglottic anteroposterior diameter and VF length (r2 = 0.78, P =. 0008), and it may be a valuable tool to infer true VF dimension in cases where disruption has occurred. The modeling data from patients with cancer did not show statistical difference to the control data, showing that accurate modeling can also be achieved in patients with laryngeal cancer.ConclusionCT scan‐based 3D modeling of the larynx and VF is possible and reproducible. The results closely match those previously reported in the literature and can also be replicated in cases with laryngeal cancer. This study paves the way for future de novo fabricated laryngeal scaffolds that can be synthesized using 3D printers and tailored to meet surgical demands.

Introduction: The purpose of this study was to compare different decellularization protocols with the conventional detergent enzymatic method (DEM) using continuous agitation. Methods: The first experiment compared conventional DEM with sonication and lyophilization+freeze-thaw cycles. A second experiment was carried out to compare time-adjusted DEM (2-hour instead of 4-hour incubations with 4% deoxycholate) to decellularization in a bioreactor. Cellularity was determined by DNA-quantitation, H&E-staining and immunostaining for major histocompatibility complex-1 (MHC-1). Results: Compared to untreated trachea, DNA content significantly decreased after 2 cycles in all groups in the first experiment and dropped below the minimal criteria for efficient decellularization (<50 ng dsDNA/mg dry weight) after 4 cycles. However, nuclei were seen in the cartilage and MCH-1 staining was detected in some submucosal areas, indicating presence of chondrocytes and cellular residues that may render the scaffold immunogenic. In the second experiment DNA content significantly decreased after 1 cycle in both groups; however, even after 4 cycles, DNA content was above the minimal criteria for efficient decellularization. While collagen-levels remained stable, glycosaminoglycans diminished significantly after the initial cycles. Conclusions: Efficient decellularization can be achieved after only 4 cycles of DEM compared to the 17 cycles previously reported. The use of a bioreactor can preserve the integrity of the extracellular matrix.

Objective The purpose of this review is to describe the recent advances in identifying possible factors involved in the pathogenesis of spasmodic dysphonia. Spasmodic dysphonia is a task‐specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. Pathogenesis of the disorder is poorly understood. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia ) and ( etiology, aetiology, diagnosis, pathogenesis , or pathophysiology ). Conclusions Several potential etiological factors have been proposed by epidemiological, genetic, and neuropathological studies. Spasmodic dysphonia is a rare disorder primarily affecting females beginning in their 40s. Vocal tremor co‐occurs in 30% to 60%. Large cohort studies identified risk factors such as a family history of neurological disorders including dystonia and tremor, recent viral illness, and heavy voice use. As none are rare events, a complex interactive process may contribute to pathogenesis in a small proportion of those at risk. Consequences to pathogenesis are neurological processes found in spasmodic dysphonia: loss of cortical inhibition, sensory processing disturbances, and neuroanatomical and physiological differences in the laryngeal motor control system. Implications for Practice Diagnosis of spasmodic dysphonia usually includes speech and laryngoscopic assessment. However, as diagnosis is sometimes problematic, measurement of neurophysiological abnormalities may contribute useful adjuncts for the diagnosis of spasmodic dysphonia in the future.

ObjectiveThe purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task‐specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties.Data SourcesPubMed, Google Scholar, and Cochrane Library.Review MethodsThe data sources were searched using the following search terms: (spasmodic dysphonia or laryngeal dystonia) and (etiology, aetiology, diagnosis, pathogenesis, or pathophysiology).ConclusionThe diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high‐speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia.Implications for PracticeA 3‐tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

Dissecting cellulitis of the scalp, or Hoffman’s disease, is a rare dermatologic condition characterized by recurrent pustules and sinus tract formation leading to scarring and alopecia. Medical management includes the use of corticosteroids, antibiotics, isotretinoin, and adalimumab. In cases where the disease is severe, refractory, and intractable, surgery is an option. We report two cases of Hoffman’s disease, where medical management failed to achieve remission. Surgical treatment was undertaken with complete resection of the affected scalp in staged procedures with subsequent split-thickness skin grafting for reconstruction. Surgery achieved both disease remission and excellent aesthetic outcomes in both patients.