Lesion-Adaptative\nBionic Tracheal Stent with Local\nPaclitaxel Release for Enhanced Therapy of Tracheal Tumor and Stenosis

The efficacy of tracheal stents (TSs) in treating malignant\ntracheal\nstenosis is often compromised by tumor overgrowth, leading to restenosis\nand other stent-related complications that conventional chemotherapy\nand commercial stents fail to adequately address. Drug-loaded tracheal\nstents have the potential to deliver chemotherapeutics directly to\ntumors while relieving stenosis, but their effectiveness has yet to\nbe studied in vivo. The design of drug-loaded tracheal stents adapting\nto lesions to achieve optimal antitumor effects and minimal side effects\nremains an area worth exploring. In this study, a lesion-adaptive\nbionic tracheal stent (PTX-TS) designed for the dual purpose of treating\ntracheal tumors and associated stenosis was developed. This novel\nPTX-TS was evaluated using an orthotopic rabbit model of malignant\ntracheal stenosis, newly established in this study. The rabbit lesions\nwere precisely scanned using computed tomography (CT) for 3D reconstruction,\nenabling the design of a PTX-TS that fit both the tumor and airway\ndimensions to ensure complete tumor coverage and effective dilation\nof the stenotic airway. The PTX-TS featured a bilayer structure including\na surface layer of PTX/ethylene-vinyl acetate copolymer (EVA) blends\nfor sustained PTX release and an inner layer of polycaprolactone (PCL)/EVA\nblends for appropriate mechanical performance. The stent was fabricated\nlayer by layer using a custom-built 3D printer, and the drug-loaded\nsurface layer was printed using a novel liquid printing technique\ndeveloped in our lab, achieving a high drug loading of up to 80%.\nThe dose of the PTX-TS was investigated and set as 7.5 mg/cm<sup>2</sup>, which leads to maximum tissue permeation. With its bionic cross-sectional\nC-shaped structure, the PTX-TS demonstrated excellent radial flexibility,\nallowing successful implantation at the lesion site using a specially\ndesigned delivery apparatus, where it self-expanded to relieve stenosis.\nAdditionally, the PTX-TS effectively delivered PTX directly to the\ntracheal tumor, resulting in superior antitumor efficacy without significant\ntoxicity or complications.