Vivero López, MaríaPereira da Mota, Ana F.Carracedo, GonzaloHuete Toral, FernandoParga Martínez, AnaOtero Casal, Ana MaríaConcheiro Nine, Ángel JoaquínÁlvarez Lorenzo, Carmen2022-12-302022-12-302022ACS Appl. Mater. Interfaces 2022, 14, 50, 55431–554461944-8244http://hdl.handle.net/10347/29671Design of advanced contact lenses (CLs) demands materials that are safe and comfortable for the wearers and that preserve the normal eye microbiota, avoiding chronic inflammation and biofilm development. This work aimed to combine the natural antibiofouling phosphorylcholine and the antioxidant and prebiotic resveratrol as integral components of CLs that may have the additional performance of preventing oxidative-stress related eye diseases. Different from previous uses of 2-methacryloyloxyethyl phosphorylcholine (MPC) as coating, we explored the feasibility of adding MPC at high proportions as a comonomer of 2-hydroxyethyl methacrylate (HEMA)-based hydrogels while still allowing for the loading of the hydrophobic resveratrol. Homogeneous distribution of MPC along the hydrogel depth (confirmed by Raman spectroscopy) notably increased solvent uptake and the proportion of free water while it decreased Young’s modulus. Relevantly, MPC did not hinder the uptake of resveratrol by CLs (>10 mg/g), which indeed showed network/water partition coefficients of >100. Protocols for CLs sterilization and loading of resveratrol under aseptic conditions were implemented, and the effects of tear proteins on resveratrol release rate were investigated. CLs sustained resveratrol release for more than 24 h in vitro, and sorption of albumin onto the hydrogel, although attenuated by MPC, slowed down the release. The combination of MPC and resveratrol reduced P. aeruginosa and S. aureus growth as tested in a novel hydrogel disk-agar interface biofilm growth setup. The developed CLs showed excellent anti-inflammatory properties and biocompatibility in in ovo and rabbit tests and provided higher and more prolonged levels of resveratrol in tear fluid, which favored resveratrol biodistribution in anterior and posterior eye segments compared to eye drops. Correlations between the release profiles of resveratrol in vitro and in vivo were assessed. Relevantly, the CLs preserved the antioxidant properties of resveratrol during the entire 8 h of wearing. In sum, CLs prepared with high proportion in MPC may help address safety and comfort requirements while having drug releasing capabilitieseng© 2022 The Authors. Published by American Chemical Society. This work is under a CC Attribution 4.0 International license (CC BY 4.0)http://creativecommons.org/licenses/by/4.0/AbsorptionBacteriaFluidsHydrogelsPhytochemistryjournal article10.1021/acsami.2c182171944-8252open access