An in situ forming thermosensitive hydrogel reprograms the ocular microenvironment for corneal alkali burn repair.

Abstract

Clinical management of acute corneal alkali burns is limited by tear washout and the failure of monotherapies to break the inflammation-neovascularization cycle. To address this, we developed a thermosensitive hydrogel (PRP/QR@gel) co-loaded with platelet-rich plasma (PRP) and quercetin (QR). The low-viscosity precursor adaptively fills irregular defects and solidifies around ocular surface temperature, establishing a tear-resistant drug depot. Mechanistically, the rapid release of hydrophilic PRP drives ordered corneal remodeling via the PI3K/Akt/mTOR pathway. Concurrently, the sustained release of hydrophobic QR scavenges ROS, suppresses NF-κB-mediated inflammation, and blocks HIF-1α/VEGF-driven pathological neovascularization. In a rabbit alkali burn model, PRP/QR@gel accelerated complete epithelialization within 7 days and reduced clinical opacity scores by 50%. This in situ-forming hydrogel offers a translatable solution for severe ocular chemical injuries.