Lesion-Adaptative Bionic Tracheal Stent with Local Paclitaxel Release for Enhanced Therapy of Tracheal Tumor and Stenosis.

The efficacy of tracheal stents (TSs) in treating malignant tracheal stenosis is often compromised by tumor overgrowth, leading to restenosis and other stent-related complications that conventional chemotherapy and commercial stents fail to adequately address. Drug-loaded tracheal stents have the potential to deliver chemotherapeutics directly to tumors while relieving stenosis, but their effectiveness has yet to be studied in vivo. The design of drug-loaded tracheal stents adapting to lesions to achieve optimal antitumor effects and minimal side effects remains an area worth exploring. In this study, a lesion-adaptive bionic tracheal stent (PTX-TS) designed for the dual purpose of treating tracheal tumors and associated stenosis was developed. This novel PTX-TS was evaluated using an orthotopic rabbit model of malignant tracheal stenosis, newly established in this study. The rabbit lesions were precisely scanned using computed tomography (CT) for 3D reconstruction, enabling the design of a PTX-TS that fit both the tumor and airway dimensions to ensure complete tumor coverage and effective dilation of the stenotic airway. The PTX-TS featured a bilayer structure including a surface layer of PTX/ethylene-vinyl acetate copolymer (EVA) blends for sustained PTX release and an inner layer of polycaprolactone (PCL)/EVA blends for appropriate mechanical performance. The stent was fabricated layer by layer using a custom-built 3D printer, and the drug-loaded surface layer was printed using a novel liquid printing technique developed in our lab, achieving a high drug loading of up to 80%. The dose of the PTX-TS was investigated and set as 7.5 mg/cm, which leads to maximum tissue permeation. With its bionic cross-sectional C-shaped structure, the PTX-TS demonstrated excellent radial flexibility, allowing successful implantation at the lesion site using a specially designed delivery apparatus, where it self-expanded to relieve stenosis. Additionally, the PTX-TS effectively delivered PTX directly to the tracheal tumor, resulting in superior antitumor efficacy without significant toxicity or complications.