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.
CONCLUSIONS: 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.
方法:通过微悬浮喉镜对23只新西兰大白兔进行内窥镜诱导SGS。对照组(n=11)仅接受EBD,研究组(n=12)接受了EBD,并植入了生物可吸收的UHD-Mg合金支架。兔子在2-,3-,SGS诱导后6周,与伤口愈合阶段相吻合。使用光学相干断层扫描(OCT),比较气道横截面积以计算连续时间点的管腔内面积的平均百分比.一种新颖的组织病理学评分系统用于分析喉气管复合体的冷冻切片。炎症程度通过炎症细胞浸润的评分变化来量化,上皮性溃疡/上皮化生,上皮下水肿/纤维化,和毛细管数/扩张。利用单变量分析来分析这些标志物。
结果:我们发现植入生物可吸收UHD-Mg合金支架的兔子在增生性变化类别中具有统计学上显着的更高得分(支架与对照:1.48vs0.46p<0.001),鳞状上皮化生(22vs5p<0.001),和腔内的中性粒细胞/纤维蛋白(31vs8,p<0.001)。单独接受EBD的兔上皮下水肿和纤维化评分更高(2.70vs3.49,p<0.0256)。与2周时的对照组相比,支架兔显示出管腔内平均面积的平均狭窄百分比显着增加(88.56vs58.98,p=0.032),然而,在所有其他时间点,腔内声门下狭窄的平均狭窄面积百分比没有显着差异。
结论:用UHD-Mg合金支架治疗的SGS兔表现出组织病理学结果提示气管纤维化水平较低。与单独的EBD相比,这可能表明狭窄发展的趋势降低。在六周结束时,支架和非支架兔之间的管腔大小没有差异。组织学上,然而,总体而言,使用可生物吸收的UHD-Mg合金支架在表面粘膜水平引起更大的组织反应,而不是在支架兔中看到的固有层纤维化。这表明更有利的愈合和更少的纤维化和狭窄的倾向,即使在该早期愈合期间从管腔尺寸的观点来看可能没有益处。与目前可用的非生物可吸收金属或硅酮基支架的已知并发症相比,这项概念验证研究强调了新型可生物降解UHD-Mg支架作为儿科SGS治疗方式的潜在用途.