In-vivo efficacy of biodegradable ultrahigh ductility Mg-Li-Zn alloy tracheal stents for pediatric airway obstruction

Laryngotracheal and subglottic stenosis are challenging airway conditions in children and adults that often necessitate repeated endoscopic procedures, tracheostomy, or open reconstruction, frequently with temporary intraluminal stenting. Commercial metal or silicone stents have suboptimal outcomes and can impede airway growth in pediatrics. Biodegradable polymer stents have been explored but are associated with migration, fragment retention, and even fatal dyspnea. This study investigates whether a novel balloon-expandable, ultra-high ductility magnesium alloy (Mg-6Li-1Zn; LZ61-KBMS) tracheal stent can maintain airway patency and then safely degrade, thereby avoiding chronic complications and permitting airway growth. The hypothesis is that UHD Mg-Li-Zn alloy stents will show favorable corrosion behavior under dynamic airway-like conditions and biocompatible in vivo degradation superior to non-degradable metallic stents.

Prior biodegradable airway stents have primarily used polymers such as PLGA, PLLA, PCL, and polydioxanone for adult and pediatric airway obstruction, but complications including stent migration, need for re-stenting, retained degradation fragments, and life-threatening dyspnea have been reported. External 3D-printed tracheal splints have alleviated obstruction without impeding growth. Metallic non-degradable tracheal stents (e.g., stainless steel) are associated with granulation and restenosis and are problematic to remove, especially in children. Biodegradable magnesium alloy tracheal stents have been piloted in rabbits, though prior alloys included rare earth elements and limited ductility. The authors previously demonstrated prototype Mg stents in a rat tracheal bypass model and characterized Mg-Li-Zn UHD alloys (notably LZ61) with ~50% ductility, low degradation rate, and biocompatibility, motivating their evaluation as pediatric airway stents.

Stent fabrication: As-cast LZ61-KBMS alloy (Mg-6Li-1Zn) was extruded into 20 mm rods, then machined into mini-tubes (4.2 mm OD, 0.3 mm wall, 60 mm length) by wire-EDM. Identical-dimension AZ31 Mg alloy and 316L stainless steel (SS) mini-tubes were prepared. Tubes were laser-cut to a CAD-designed stent pattern and electrochemically polished using a custom setup (stent on Mg or SS wire as anode, Pt cathode, acid electrolyte; parameters per Supplementary Tables). Post-polish stents were rinsed and dried. In vitro degradation under flow: LZ61-KBMS and AZ31 stents were balloon-mounted (5 mm × 2 cm), deployed into silicone tubes, and immersed in circulating Hanks' balanced salt solution within a 3D CulturePro bioreactor at 80 ml/min. Stents (n=3 per alloy) were µCT scanned at 1, 3, and 5 weeks to reconstruct 3D structure and quantify remaining volume. After 5 weeks, dried stents were examined by SEM and EDAX to characterize surface layers and elemental composition (O, Mg, Ca, P). In vivo rabbit study: Female New Zealand white rabbits (12 weeks old) underwent midline neck incision and cricoidotomy; stents (LZ61-KBMS or 316L SS) were balloon-expanded to 12 atmospheres for 30 s beneath the first airway cartilage ring and sutured to prevent migration. Groups of 5 animals per stent type were used for each endpoint (4, 8, 12 weeks). Immediate post-op X-rays confirmed placement. At endpoints, endoscopy and optical coherence tomography (OCT) assessed airway lumen and stent/tissue interface; OCT-based lumen area was quantified (n=3; ImageJ). Explanted tracheas underwent µCT for remaining stent volume and 3D reconstruction. Histology included H&E for morphology, Alcian blue for mucus/goblet cells (quantified as number per 1 mm of epithelium), and CD68 immunostaining for macrophages. Lung, liver, and kidney were also examined for systemic toxicity. Statistics: Mean ± SD; one-way ANOVA with Bonferroni post hoc; p<0.05 significant.

- In vitro flow bioreactor: LZ61-KBMS exhibited substantially slower degradation than AZ31 under dynamic HBSS flow. At 5 weeks, LZ61-KBMS had 47.6% volume loss (i.e., 52.4% remaining), whereas AZ31 had only 7.8% of initial volume remaining. SEM/EDAX after 5 weeks showed more Ca and P deposited on LZ61 surfaces, suggesting a more protective Ca/P-rich degradation layer compared to AZ31. - In vivo rabbit trachea: LZ61-KBMS degraded progressively with 53 ± 12% volume loss at 4 weeks and complete degradation by 8 weeks (µCT, endoscopy, OCT). H2 gas pockets were observed around LZ61-KBMS during degradation by OCT but were not associated with adverse tissue effects. In contrast, 316L SS stents maintained structure throughout 12 weeks. - Airway growth and patency: Tracheal lumen area increased over time in LZ61-KBMS-implanted airways, indicating no interference with airway growth. The 316L SS group exhibited decreasing lumen area with significant stenosis at 8 and 12 weeks relative to LZ61-KBMS (p<0.01, n=3). - Histology and biocompatibility: LZ61-KBMS at 4 weeks showed localized inflammatory cellularity near struts and thicker mucus, normalizing by 8 and 12 weeks with restored epithelium and normal mucus secretion. Goblet cell counts showed no significant differences among groups (P>0.05). CD68 staining revealed macrophage clusters at 4 weeks for LZ61-KBMS that resolved by 8–12 weeks; macrophage clusters persisted in 316L SS at 8 and 12 weeks. No pathology was observed in lung, kidney, or liver across groups.

The study demonstrates that an ultra-high ductility Mg-Li-Zn alloy (LZ61-KBMS) tracheal stent can maintain airway patency and then fully resorb within approximately 8 weeks in a rabbit model, enabling continued airway growth and avoiding chronic complications associated with non-degradable metallic stents. Superior corrosion resistance of LZ61-KBMS under dynamic flow relative to AZ31 is attributed to a more adherent Ca/P-rich surface layer, aligning with known flow-induced mechanisms that typically accelerate Mg corrosion. Bioreactor-derived corrosion rates closely matched early in vivo rates, indicating relevancy of the flow model to airway conditions. Importantly, unlike 316L SS, LZ61-KBMS did not provoke progressive stenosis; instead, airway lumen increased over time, and post-degradation histology resembled healthy tissue with resolution of macrophage clusters. Hydrogen gas pocket formation, a known phenomenon for Mg alloys, did not detrimentally affect airway tissue in this setting, likely due to airway venting. Collectively, findings support the premise that UHD magnesium alloy stents can deliver temporary mechanical support and then safely degrade, potentially offering a clinically advantageous option for pediatric airway obstruction management.

LZ61-KBMS, a novel ultra-high ductility Mg-Li-Zn alloy tracheal stent, showed feasible deployment, controlled degradation with complete resorption by 8 weeks, maintenance of airway patency, compatibility with airway growth, and favorable local and systemic biocompatibility in a rabbit model. These results suggest a promising pathway to a new treatment modality for pediatric airway obstruction that obviates the need for device removal and mitigates risks associated with permanent stents. Future work should elucidate full degradation mechanisms, optimize stent microstructure and corrosion-resistant coatings, develop a minimally invasive endoscopic balloon delivery system, evaluate mechanical performance against clinical requirements, and validate efficacy and safety in disease-relevant models (e.g., subglottic stenosis) and larger/longer-term studies, including detailed analyses of corrosion products.

In vivo testing was performed in healthy rabbit tracheas rather than a stenosis model, limiting direct assessment of therapeutic efficacy in diseased airways. The delivery approach involved a neck incision rather than an endoscopic, fully minimally invasive method. Detailed mechanisms of degradation (corrosion versus fracture, role of cyclic mechanical loading and stress corrosion cracking) were not fully characterized. AZ31 alloy was not assessed in vivo for comparison. Certain outcomes (e.g., lumen area by OCT) had smaller analyzed sample sizes (n=3). Long-term outcomes beyond 12 weeks and comprehensive quantification of residual corrosion products in vivo were not provided.