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Abstract Background Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube. Methods A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing. Results Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time. Conclusion The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.

Abstract Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p

Abstract Objective Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug‐eluting electrospun polymer‐mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Methods Dexamethasone‐loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated‐indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two‐way ANOVA with Tukey's post hoc test and Wilcoxon rank‐sum test. Results VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p

Abstract Objectives/hypothesis Composite vocal fold (VF) biomechanical data are lacking for augmentation after recurrent laryngeal nerve (RLN) injury. We hypothesize resulting atrophy decreases VF stiffness and augmentation restores native VF biomechanics. Methods Sixteen Yorkshire Crossbreed swine underwent left RLN transection and were observed or underwent carboxymethylcellulose (CMC) or calcium hydroxyapatite (CaHa) augmentation at 2 weeks. Biomechanical measurements (structural stiffness, displacement, and maximum load) were measured at 4 or 12 weeks. Thyroarytenoid (TA) muscle cross‐sectional area was quantified and compared with two‐way ANOVA with Tukey's post hoc test. Results After 4 weeks, right greater than left structural stiffness (mean ± SE) was observed (49.6 ± 0.003 vs. 28.4 ± 0.002 mN/mm), left greater than right displacement at 6.3 mN (0.54 ± 0.01 vs. 0.46 ± 0.01 mm, p