Pathology-responsive light-triggered conjunctival adhesive implantable hydrogels for effective anti-scarring after glaucoma filtering surgery

Glaucoma filtration surgery (GFS) frequently fails due to uncontrolled subconjunctival scarring, driven by a cascade of postoperative inflammation, oxidative stress, and exaggerated myofibroblast activation. To address this, we developed an in-situ light-triggered hydrogel that enables strong conjunctival adhesion, bleb mechanical support, and pathology-responsive smart drug delivery for effective bleb scarring inhibition. The crosslinked hydrogel system prepared from functionalized carboxymethyl chitosan and epigallocatechin gallate (EGCG), prior to ultraviolet light (UV) exposure, was denoted as PNE hydrogel. After injection, PNE can adapt to ocular anatomy, and subsequent transconjunctival light exposure rapidly activates hydrogel crosslinking and covalent tissue adhesion, generating a mechanically robust hydrogel, denoted as PNE-UV hydrogel. Meanwhile, light-induced surface property changes further enhance conjunctival adhesion and reduce interface inflammatory cell infiltration. Concurrently, light-induced hydrophilic-to-hydrophobic hydrogel surface transition promotes water exclusion, further enhancing tissue adhesion to minimize interface inflammatory cell infiltration. With adequate mechanical strength, rapid self-healing, and good biosafety, PNE-UV provides essential mechanical bleb support during wound healing. Crucially, elevated postoperative Reactive Oxygen Species (ROS) triggers intelligent EGCG release for over 17 days, which not only effectively scavenges ROS and promotes macrophage M1-to-M2 polarization to mitigate inflammation, but also suppresses TGF-β1-induced conjunctival fibroblast-to-myofibroblast transdifferentiation and myofibroblast proliferation. In a rabbit model of filtration surgery, PNE-UV hydrogel significantly prolonged bleb survival, reduced intraocular pressure, and decreased Collagen deposition via mitigating oxidative stress and inflammation and suppressing fibrotic processes. Collectively, this interfacial adhesion and precise immunomodulation hydrogel presents an effective and clinically translatable strategy for post-GFS scarring prevention.

Adhesive hydrogel; Anti-scarring therapy; Glaucoma filtering surgery; Inflammatory and oxidative stress; ROS response.