Degrees of Inflammation in the Treatment of Subglottic Stenosis in a Rabbit Model: Histopathological Assessment of a Novel Bioabsorbable Ultra-high Ductility Magnesium Alloy Stent.

ABSTRACT

OBJECTIVE: Utilizing a novel histopathological scoring system and subglottic stenosis (SGS) rabbit model, we aimed to compare degrees of inflammation and severity of narrowing in the subglottis between two minimally invasive therapeutic modalities endoscopic balloon dilation (EBD) alone versus EBD with placement of a bioabsorbable ultra-high ductility magnesium (UHD-Mg) alloy stent. METHODS: SGS was induced endoscopically via microsuspension laryngoscopy in 23 New Zealand white rabbits. The control group (n = 11) underwent EBD alone, the study arm (n = 12) underwent EBD with implantation of bioabsorbable UHD-Mg alloy stents. Rabbits were euthanized at 2-, 3-, and 6-weeks after SGS induction, coinciding with wound healing stages. Using Optical Coherence Tomography (OCT), cross-sectional areas of airways were compared to calculate the mean percentage of intraluminal area at sequential time points. A novel histopathological scoring system was used to analyze frozen sections of laryngotracheal complexes. The degree of inflammation was quantified by scoring changes in inflammatory cell infiltration, epithelial ulceration/metaplasia, subepithelial edema/fibrosis, and capillary number/dilation. Univariate analysis was utilized to analyze these markers. RESULTS: We found rabbits implanted with the bioabsorbable UHD-Mg alloy stent had statistically significantly higher scores in categories of hyperplastic change (stents vs controls 1.48 vs 0.46 p < 0.001), squamous metaplasia (22 vs 5 p < 0.001), and neutrophils/fibrin in lumen (31 vs 8, p < 0.001). Rabbits who received EBD alone had higher scores of subepithelial edema and fibrosis (2.70 vs 3.49, p < 0.0256). The stented rabbits demonstrated significantly increased mean percent stenosis by intraluminal mean area compared to controls at 2 weeks (88.56 vs 58.98, p = 0.032), however at all other time points there was no significant difference between intraluminal subglottic stenosis by mean percent stenosis area. DISCUSSION: Rabbits with SGS treated with UHD-Mg alloy stents demonstrated histopathologic findings suggestive of lower levels of tracheal fibrosis. This could indicate a reduced tendency towards the development of stenosis when compared to EBD alone. There was not a difference in luminal size between stent and non-stented rabbits at the six-week end point. Histologically, however, overall the use of bioabsorbable UHD-Mg alloy stenting elicited a greater tissue response at the level of the superficial mucosa rather than fibrosis of the lamina propria seen in the stented rabbits. This suggests more favorable healing and less of a tendency towards fibrosis and stenosis even though there may not be a benefit from a luminal size standpoint during this early healing period. Compared to known complications of currently available non-bioabsorbable metal or silicone-based stents, this proof-of-concept investigation highlights the potential use of a novel biodegradable UHD-Mg stent as a therapeutic modality for pediatric SGS.