Advances in loading-release-repair strategies of hydrogels for anterior segment disease therapy

Anterior segment (AS) diseases are a major group of ocular disorders that impair ocular surface homeostasis, optical transparency, aqueous humor circulation, and postoperative visual quality, including Dry Eye Disease (DED), corneal injury, Infectious Keratitis (IK), uveitis, glaucoma, and Posterior Capsule Opacification (PCO). The therapeutic goal of these diseases extends beyond symptom relief toward the establishment of integrated treatment systems capable of overcoming complex ocular barriers and actively regulating the pathological immune microenvironment and inflammatory cascades through efficient drug loading, controlled release, and tissue repair. However, conventional ophthalmic formulations such as eye drops and ointments remain limited by tear dilution, blinking clearance, nasolacrimal drainage, corneal epithelial barriers, restriction by the Blood-Aqueous Barrier (BAB), and poor long-term compliance, making it difficult to maintain effective drug concentrations at lesion sites. Hydrogels, composed of hydrated polymeric networks, have emerged as promising platforms for AS disease therapy owing to their excellent biocompatibility, transparency, tunable mechanical properties, tissue adhesiveness, stimuli responsiveness, and extracellular matrix (ECM)-mimicking structures. Depending on clinical requirements, hydrogels can be engineered into adhesive eye drops, thermosensitive in situ gels, corneal repair scaffolds, drug-eluting contact lenses, intracapsular drug reservoirs, and functionalized intraocular lenses (IOLs) to prolong ocular retention, enhance trans-barrier delivery, reduce administration frequency, and remodel the pathological microenvironment through anti-inflammatory, immunoregulatory, antioxidative, antibacterial, pro-regenerative, and anti-fibrotic effects. Centered on the "loading-release-repair" principle, this review systematically summarizes material design, functional mechanisms, and application advances of hydrogels in the treatment of prevalent AS diseases, aiming to provide insights for performance optimization, disease-specific adaptation, and clinical translation of next-generation ocular hydrogels with immune-microenvironment targeting capabilities.