A metal-organic framework-based trilayer biomimetic coating on lacrimal stents for dual-drug therapy to prevent restenosis

Postoperative reocclusion remains a major challenge in lacrimal duct stent implantation, primarily driven by persistent inflammation and fibrosis. To address this issue, we developed a coating system that integrates drug release with interfacial bioactivity regulation. A polydopamine-hybridized zeolitic imidazolate framework (pZIF-8) was synthesized via a one-pot method and co-loaded with mometasone furoate (Elocon Cream) and verteporfin (anti-fibrotic) to construct a reactive oxygen species (ROS)/pH responsive nanocarrier. A trilayered coating consisting of a polydopamine (PDA) adhesive layer, a drug-loaded pZIF-8 middle layer, and an outermost hyaluronic acid (HA) antifouling layer was assembled on a silicone stent using a layer-by-layer approach. In vitro, the coating exhibited significantly reduced protein adsorption and bacterial adhesion compared to Control, supported >75% viability of epithelial cells (RPMI 2650) while reducing macrophage (RAW 264.7) viability to approximately 2% and fibroblast (L929) viability to below 50% of Control, and achieved sustained drug release under inflammatory conditions (pH 6.0 + 0.1 mM H₂O₂). In a rabbit lacrimal duct model, the coated stent attenuated acute inflammation, reduced collagen deposition, and downregulated YAP1 expression compared to bare stents. Immunofluorescence analysis showed that bare stents promoted M2a macrophage polarization, whereas the coated stent promoted M2b polarization, as indicated by negative CD68/CD206 colocalization. These findings demonstrate a coating system that combines a ROS/pH-responsive nanocarrier with an antifouling surface to target inflammation and fibrosis. This approach may offer a strategy for preventing stent restenosis and could be adapted for other implantable luminal devices. STATEMENT OF SIGNIFICANCE: Lacrimal stent implantation is frequently complicated by restenosis due to postoperative inflammation and fibrosis. Current stents serve as passive mechanical supports and do not actively intervene in this pathological process. Here we report a metal-organic framework (MOF)-based trilayer coating designed to address both inflammation and fibrosis. The coating consists of a polydopamine adhesive layer, a pZIF-8 MOF layer co-loaded with mometasone furoate (Elocon Cream) and verteporfin (anti-fibrotic), and an outermost hyaluronic acid antifouling layer. The pZIF-8 nanocarrier exhibits ROS/pH-responsive degradation, while the HA outer layer provides sustained release and antifouling properties. This design may offer a strategy to prevent restenosis and could inform the design of other implantable luminal devices.