Clin Exp Otorhinolaryngol.  2021 Aug;14(3):328-337. 10.21053/ceo.2020.01627.

Endoscopically Applied Biodegradable Stent in a Rabbit Model of Pediatric Tracheomalacia

• Choi JS
• Seok J
• Eom MR
• Jung E
• Park SA
• Joo SM
• Jun YJ
• Son KW
• Kwon SK

• KMID: 2519188
• DOI: http://doi.org/10.21053/ceo.2020.01627

Abstract

Objectives
. A polydioxanone (PDO) stent was developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia-model rabbits.
Methods
. In total, 29 New Zealand white rabbits were used: 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. The tracheomalacia model was successfully established in 12 rabbits, and PDO stents were placed in eight of those rabbits.
Results
. The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and the mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia-model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0±6.8 and 1.0±0.8 days, respectively. Thus, the PDO stent yielded a significant survival gain (P=0.001). In the tracheomalacia rabbits, stent degradation and granulation tissue were observed 7 weeks after placement, leading to airway collapse and death.
Conclusion
. We successfully developed a PDO stent and an endoscopic guide placement system. The degradation time of the stent was around 10 weeks in normal rabbits, and its degradation was accelerated in the tracheomalacia model. The mucosal changes associated with PDO stent placement were reversible. Placement of the PDO stent prolonged survival in tracheomalacia-model rabbits.

Keyword

Tracheomalacia; Therapeutics; Trachea; Stents; Absorbable Implants; Polydioxanone; Pediatrics

Figure

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  Fig. 1 Polydioxanone (PDO) tracheal stent and endoscopic delivery tools. (A) PDO stent (8×30 mm). (B, C) Transoral tracheal stent delivery system.

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  Fig. 2 Flowchart of animal experiments. The number of rabbits used in each experiment, and the time and purpose of their sacrifice are shown. PDO, polydioxanone; 3D, three-dimensional; micro-CT, micro-computed tomography.

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  Fig. 3 Schematic representation showing the process of how to develop the tracheomalacia rabbit model. PDO, polydioxanone.

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  Fig. 4 Microscopic images of in vitro degradation of the polydioxanone (PDO) stent at (A) 0, (B) 4, (C) 8, (D) 12, (E) 16, and (F) 20 weeks following stent placement (magnification, ×28). (G) Mechanical strength of PDO stent after degradation in vitro (*P<0.001).

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  Fig. 5 Bronchoscopy images taken (A) immediately after stenting and (B) 1, (C) 2, (D) 4, (E) 6, (F) 8, (G) 10, and (H) 12 weeks after stenting. (G) At 10 weeks, the stent had decomposed, and debris was observed. (H) At 12 weeks, no material was observed inside the trachea.

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  Fig. 6 Histological evaluation of the airway epithelium of the normal trachea at (A) 1, (B) 4, (C) 8, and (D) 12 weeks after stenting and (E) no stenting. Collagen is stained blue by Masson’s trichrome. Mucin is stained blue by Alcian blue. Nuclei are stained blue by 4′,6-diamidino-2-phenylindole (DAPI) in immunohistochemistry against CK5 and β-tubulin. The location from which each tissue was sampled is marked in red in Supplementary Fig. 2.

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  Fig. 7 Survival of tracheomalacia animals with and without stents. All tracheomalacia rabbits without stents died within 2 days. The survival duration of rabbits with stents was significantly longer than rabbits without stents (49.0±6.8 vs. 1.0±0.8 days, P=0.001).

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  Fig. 8 Serial endoscopic images of the airway (A) after creating tracheomalacia, (B) after stenting, and (C) 1, (D) 2, (E) 4, (F) 6, and (G, H; postmortem) 7 weeks after stenting. Yellow arrows (G, H) show a degraded polydioxanone stent.

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  Fig. 9 Reconstructed micro-computed tomography images of the trachea (A) without a stent 1 day after the induction of tracheomalacia and (B–D) with a stent at (B) 4, (C) 7, and (D) 8 weeks after stenting. The upper and lower panels represent axial and longitudinal views, respectively. PDO, polydioxanone.

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