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.

Autor: McCarty EB; Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Eye & Ear Institute, Suite 500, Pittsburgh, PA, 15213, USA. Electronic address: mccartyeb@upmc.edu., Bertoni D; Department of Otolaryngology - Head & Neck Surgery, Sidney Kimmel Medical College, 925 Chestnut Street, 6th Floor, Philadelphia, PA, 19107, USA. Electronic address: Dylan.Bertoni@jefferson.edu., Patel T; Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Eye & Ear Institute, Suite 500, Pittsburgh, PA, 15213, USA. Electronic address: patelt5@upmc.edu., Jaramillo C; Department of Pathology & Laboratory Services, Brooke Army Medical Center, 3551 Roger Brooke Dr, Fort Sam, Houston, TX, 78234, USA. Electronic address: couger.a.JimenezJaramillo.mil@health.mil., Tobey ABJ; Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Eye & Ear Institute, Suite 500, Pittsburgh, PA, 15213, USA. Electronic address: allison.tobey@chp.edu., Kumta PN; Department of Bioengineering, Swanson School of Engineering, 815C Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA; Department of Chemical and Petroleum Engineering, Swanson School of Engineering, 815C Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA; Department of Mechanical Engineering and Materials Science, Swanson School of Engineering, 815C Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA. Electronic address: pkumta@pitt.edu., Chi D; Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Eye & Ear Institute, Suite 500, Pittsburgh, PA, 15213, USA. Electronic address: david.chi@chp.edu., Mady LJ; Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Eye & Ear Institute, Suite 500, Pittsburgh, PA, 15213, USA. Electronic address: lmady1@jh.edu.
Jazyk: angličtina
Zdroj: International journal of pediatric otorhinolaryngology [Int J Pediatr Otorhinolaryngol] 2024 Jun; Vol. 181, pp. 111994. Date of Electronic Publication: 2024 May 27.
DOI: 10.1016/j.ijporl.2024.111994
Abstrakt: 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.
Competing Interests: Declaration of competing interest There are no declarations of interest for this project. However it is important to note that the funding for this research was supported by The Centralized Otolaryngology Research Efforts (CORE) grant program through the American Academy of Otolaryngology- Head and Neck Surgery. UHD-Mg alloy processing and stent fabrication was supported by the National Science Foundation Funded Engineering Research Center – Revolutionizing Metallic Biomaterials (ERC-RMB), Grant # EEC – 0812348.
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Databáze: MEDLINE