Electrospun Lacrimal Stent for Synergistic Anti-inflammatory and Antioxidant Therapy via Macrophage Polarization and Microenvironment Remodeling.

Abstract

Obstructive lacrimal duct disease has long been a clinical challenge due to the limitations of traditional silicone stents, which are functionally simple, non-degradable, and prone to fibrosis-induced restenosis. In this study, we present a breakthrough approach in the development of a multifunctional, drug-loaded, biodegradable lacrimal duct stent based on electrospinning technology. By integrating mesoporous polydopamine nanoparticles loaded with dexamethasone (MPDA@DEX) into a PLCL/Gel composite matrix, we successfully fabricated a biomimetic stent that exhibits desirable mechanical properties, hydrophilic surface characteristics, and controlled drug release capabilities. In vitro, the stent demonstrated excellent anti-inflammatory and antioxidant activities, being associated with a shift of macrophages toward an M2-like phenotype, significantly reducing intracellular ROS levels, and contributing to an inflammation-repair balance via modulation of the MAPK/Hippo/FoxO signaling pathways. Transcriptomic sequencing further confirmed its ability to coordinate the regulation of the cellular transcription network, simultaneously suppressing pro-inflammatory pathways while activating repair mechanisms. In vivo experiments further validated the stent's capacity to significantly reduce inflammation at the implantation site, inhibit collagen deposition, and promote angiogenesis. This research provides an innovative solution for lacrimal duct repair with active regulatory functions, representing a promising transition from "passive support" to "active repair" in therapeutic strategies.