Advancing Laryngeal Adductor Reflex Testing Beyond Sensory Threshold Detection.

Flexible endoscopic evaluation of swallowing with sensory testing (FEESST) is a promising clinical tool to assess airway integrity via the laryngeal adductor reflex (LAR). The current clinical protocol relies on sensory threshold detection, as relatively little is known about the motor response of this sensorimotor airway protective reflex. Here, we focused on characterizing normative LAR motion dynamics in 20 healthy young participants using our prototype high-pressure syringe-based air pulse device and analytic software (VFtrack™) that tracks vocal fold (VF) motion in endoscopic videos. Following device bench testing for air pulse stimulus characterization, we evoked and objectively quantified LAR motion dynamics in response to two suprathreshold air pulse stimuli (40 versus 60 mm Hg), delivered to the arytenoid mucosa through a bronchoscope working channel. The higher air pressures generated by our device permitted an approximate 1 cm endoscope working distance for continual visualization of the bilateral VFs throughout the LAR. Post hoc video analysis identified two main findings: (1) there are variant and invariant subcomponents of the LAR motor response, and (2) only a fraction of suprathreshold stimuli evoked complete glottic closure during the LAR. While the clinical relevance of these findings remains to be determined, we have nonetheless demonstrated untapped potential in the current FEESST protocol. Our ongoing efforts may reveal LAR biomarkers to quantify the severity of laryngeal pathology and change over time with natural disease progression, spontaneous recovery, or in response to intervention. The ultimate goal is to facilitate predictive modeling of patients at high risk for dysphagia-related aspiration pneumonia.

Strategic Design of Antimicrobial Hydrogels Containing Biomimetic Additives for Enhanced Matrix Responsiveness and HDFa Wound Healing Rates.

Supramolecular nanocomposite materials have emerged as a leading interdisciplinary research area that exploits synergistic relationships at the nanoscale to enhance the properties (mechanical and chemical) of next-generation biopolymeric materials. Hydrogels synthesized from natural biopolymers have emerged because of their intrinsic properties such as noncytotoxicity and biodegradability as well as their well-defined three-dimensional, noncovalent network that is ideal for modification and functionalization. Therefore, it is critical to develop a mechanistic understanding tailored to the nuances involved in the interactions of the biopolymer scaffold with the functional additives present in these complex matrixes. This work will discuss the strategic design of hydrogels placing emphasis on the selection of the biopolymer network and the critical role that the incorporation of additives such as biomimetic cross-linking agents (lactones/amino acids) and antimicrobial nanoparticles (NPs) has on the properties and responsiveness of the final nanocomposite. Results have shown that the hydrogen bonding capacity of the biomimetic additives and antimicrobial agents (i.e., AgNPs) impacts the packing density of the hydrogel network and therefore modulates the resultant swellability. Furthermore, the addition of Ag-coated TiO2 NPs (Ag/TiO2 NPs) and biomimetic additives provided antimicrobial activity along with enhanced closure rates of simulated wounds in adult human dermal fibroblasts.

A Surgical Mouse Model for Advancing Laryngeal Nerve Regeneration Strategies.

Iatrogenic recurrent laryngeal nerve (RLN) injury is a morbid complication of anterior neck surgical procedures. Existing treatments are predominantly symptomatic, ranging from behavioral therapy to a variety of surgical approaches. Though laryngeal reinnervation strategies often provide muscle tone to the paralyzed vocal fold (VF), which may improve outcomes, there is no clinical intervention that reliably restores true physiologic VF movement. Moreover, existing interventions neglect the full cascade of molecular events that affect the entire neuromuscular pathway after RLN injury, including the intrinsic laryngeal muscles, synaptic connections within the central nervous system, and laryngeal nerve anastomoses. Systematic investigations of this pathway are essential to develop better RLN regenerative strategies. Our aim was to develop a translational mouse model for this purpose, which will permit longitudinal investigations of the pathophysiology of iatrogenic RLN injury and potential therapeutic interventions. C57BL/6J mice were divided into four surgical transection groups (unilateral RLN, n = 10; bilateral RLN, n = 2; unilateral SLN, n = 10; bilateral SLN, n = 10) and a sham surgical group (n = 10). Miniaturized transoral laryngoscopy was used to assess VF mobility over time, and swallowing was assessed using serial videofluoroscopy. Histological assays were conducted 3 months post-surgery for anatomical investigation of the larynx and laryngeal nerves. Eight additional mice underwent unilateral RLN crush injury, half of which received intraoperative vagal nerve stimulation (iVNS). These 8 mice underwent weekly transoral laryngoscopy to investigate VF recovery patterns. Unilateral RLN injury resulted in chronic VF immobility but only acute dysphagia. Bilateral RLN injury caused intraoperative asphyxiation and death. VF mobility was unaffected by SLN transection (unilateral or bilateral), and dysphagia (transient) was evident only after bilateral SLN transection. The sham surgery group retained normal VF mobility and swallow function. Mice that underwent RLN crush injury and iVNS treatment demonstrated accelerated and improved VF recovery. We successfully developed a mouse model of iatrogenic RLN injury with impaired VF mobility and swallowing function that can serve as a clinically relevant platform to develop translational neuroregenerative strategies for RLN injury.

Mice Lacking Brain-Derived Serotonin Have Altered Swallowing Function.

The intricate sensorimotor neural circuits that control swallowing are heavily reliant on serotonin (5-hydroxytryptamine [5-HT]); however, the impact of 5-HT deficiency on swallow function remains largely unexplored. We investigated this using mice deficient in tryptophan-hydroxylase-2 (TPH2), the enzyme catalyzing the rate-limiting step in 5-HT synthesis. Videofluoroscopy was utilized to characterize the swallowing function of TPH2 knockout (TPH2-/-) mice as compared with littermate controls (TPH2+/+). Results showed that 5-HT deficiency altered all 3 stages of swallowing. As compared with controls, TPH2-/- mice had significantly slower lick and swallow rates and faster esophageal transit times. Future studies with this model are necessary to determine if 5-HT replacement may rescue abnormal swallowing function. If so, supplemental 5-HT therapy may have vast applications for a large population of patients with a variety of neurologic disorders resulting in life-diminishing dysphagia, particularly amyotrophic lateral sclerosis and Parkinson's disease, for which 5-HT deficiency is implicated in the disease pathogenesis.