COF-reinforced tunable-degradation 5-FU@COF/PLLA-TPU coating with dual anti-sludge and anti- tumor hyperplasia for biliary stent restenosis prevention

To overcome biliary stent failures caused by biofilm formation, bile sludge accumulation, and tumor-mediated restenosis, we designed a self-polishing, biodegradable coating by flame-spraying poly(L-lactic acid)/thermoplastic polyurethane (PLLA/TPU) composites incorporated with 5-fluorouracil-loaded covalent organic frameworks (5-FU@COF). This strategy integrates: 1) Programmable self-polishing via synergistic PLLA ester/urethane bond hydrolysis and pH-sensitive COF delamination, ensuring controlled erosion; 2) Mechanoadaptive reinforcement, where 5-FU@COF enhances coating-substrate adhesion by 111% (10FCLU: 3.19 MPa vs. LU:1.51 MPa) through COFs rigid filler anchoring and stress homogenization; and 3) Dual anti-biliary sludge accumulation/tumoricidal therapy enabled by 216.5 nm COF nanospheres achieving 43.1% 5-FU loading. The coatings resist biofouling via electrostatic repulsion and dynamic polishing, reducing bile salt coverage to 11.53% (vs. 47.44% on bare Ti). Biphasic 5-FU release from 10FCLU coating achieves 92.6% tumor Cholangiocarcinoma cell (RBE) inhibition for 3 days, validated by TEM ultrastructural apoptosis markers (nuclear fragmentation; mitochondrial collapse) and Korsmeyer-Peppas release kinetics. This multifunctional drug-loading coating enables next-generation biliary stents with sustained patency.