Laryngotracheal stenosis (LTS) and subglottic stenosis (SGS) pose significant challenges in both adult and pediatric populations. Current treatment options, including endoscopic procedures, tracheostomy, and open surgical repair, often lead to complications such as recurrent scarring, poor wound healing, and life-threatening anastomotic disruption. In pediatric patients, the situation is further complicated by the need to minimize interference with airway growth. Intraluminal stenting is sometimes employed to provide graft stability and reinforcement, but commercial metal or silicone stents do not always yield optimal outcomes, even in adults. The development of advanced biomaterials-based airway stents offers the potential for a less invasive, reduced-morbidity treatment option. Previous research has explored degradable polymeric stents, but complications such as stent migration, degradation fragment retention, and fatal dyspnea have been reported. This study explores a novel approach utilizing a biodegradable magnesium alloy to overcome the limitations of existing technologies, addressing the need for a stent that maintains airway patency while safely degrading over time, thereby minimizing long-term complications and allowing for natural airway growth in children.

Preclinical and clinical studies have investigated the use of biodegradable polymeric tracheal stents made from materials such as poly(lactic-co-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA), polycaprolactone (PCL), and polydioxanone. While these materials offer biodegradability, significant drawbacks include stent migration, the need for repeated stenting, retention of degradation fragments, and even fatal dyspnea. In contrast, 3D-printed external tracheal splints have shown promise in alleviating obstructive symptoms without inhibiting airway growth. However, current biodegradable tracheal stents often mimic the design of non-degradable metallic stents, proving ineffective for pediatric airway obstruction. This study builds upon recent work demonstrating the feasibility of biodegradable magnesium alloy pediatric tracheal stents in a rabbit model, but advances this by focusing on a high-ductility magnesium alloy specifically designed for this application.

This study investigated a novel balloon-expandable ultra-high ductility (UHD) biodegradable magnesium tracheal stent (LZ61-KBMS) made from a Mg-6Li-1Zn (LZ61) alloy. The stent fabrication involved extrusion of the LZ61-KBMS alloy into rods, followed by wire-electrical discharge machining (wire-EDM) to create mini-tubes. Laser cutting was then used to create the stent structure, and finally, the stents underwent electrochemical polishing to achieve a smooth surface. *In vitro* degradation was evaluated in a bioreactor simulating dynamic fluid flow, comparing LZ61-KBMS to a commercial high corrosion-resistant magnesium alloy (AZ31). *In vivo* degradation and tissue response were assessed by implanting LZ61-KBMS stents into healthy rabbit tracheas, with 316L stainless steel stents serving as a non-degradable control. The study employed various techniques to assess stent degradation and tissue response including micro-computed tomography (µCT) for 3D reconstruction of stent structure, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX) for surface analysis, endoscopy and optical coherence tomography (OCT) for in-vivo stent visualization, and histological analysis (H&E, Alcian blue, and CD68 immunostaining) to evaluate tissue morphology, mucus production, and inflammatory response. Tracheal lumen size was measured using ImageJ software from OCT images.

The *in vitro* bioreactor study showed that LZ61-KBMS degraded significantly slower than AZ31 under dynamic flow conditions. After 5 weeks, 47.6% of the LZ61-KBMS stents remained, while AZ31 stents were almost completely degraded. EDAX analysis revealed higher calcium and phosphorus deposits on the LZ61-KBMS stent surface, suggesting a more stable and protective degradation layer. *In vivo*, LZ61-KBMS stents showed complete degradation within 8 weeks, with no visible stenotic tissue formation and restoration of the normal tracheal lumen. In contrast, the 316L SS control group exhibited significant stenotic tissue growth. Tracheal lumen size measurements showed a steady increase in the LZ61-KBMS group, reflecting normal airway growth, while the 316L SS group showed a decrease in lumen size. Histological analysis revealed that at 4 weeks, the LZ61-KBMS stents were embedded in airway tissue with an inflammatory response, but by 8 and 12 weeks, the epithelium was fully restored. No systemic toxicity was observed in the lung, kidney, or liver. Alcian blue staining indicated a temporary increase in mucus secretion at week 4, but normal mucus production was observed at later time points. CD68 immunostaining showed macrophage clusters at week 4 in the LZ61-KBMS group, resolving by 8 and 12 weeks. The 316L SS group showed persistent macrophage clusters.

The findings demonstrate that the LZ61-KBMS stents offer superior performance compared to traditional non-degradable metallic stents. The controlled degradation rate of the LZ61-KBMS alloy, influenced by alloy composition, electrolyte, and external stress, allowed for complete degradation without impeding airway growth. The bioreactor study effectively mimicked the dynamic in vivo environment. The *in vivo* results highlight the advantages of the LZ61-KBMS stent, particularly the absence of stenosis formation and the maintenance of normal airway growth. While hydrogen gas pocket formation was observed, it appeared harmless. The histological analysis confirmed good biocompatibility and the absence of long-term inflammatory responses. The lack of persistent degradation products is attributed to the solubility of the magnesium-based corrosion products and the dynamic nature of the airway environment.

This study demonstrates the feasibility of using a novel ultra-high ductility biodegradable magnesium alloy (LZ61-KBMS) tracheal stent. The stent showed complete degradation within 8 weeks in a rabbit model without hindering airway growth or causing significant adverse tissue reactions. While the pre-clinical data is promising, future studies are needed to optimize stent design, investigate the degradation mechanisms in greater detail, test in stenosis models, and develop non-invasive delivery methods. This novel approach offers a potential new treatment modality for airway obstruction that avoids the long-term risks associated with permanent stents.

The study used a healthy rabbit model; further investigation in a clinically relevant stenosis model is necessary. The stents were surgically implanted; a less invasive delivery system is needed for clinical translation. Long-term studies are required to fully assess the biocompatibility and degradation profile of the stents. The impact of the hydrogen gas formation on long-term tissue response needs further evaluation.