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The eyeball possesses sophisticated anatomical and physiological characteristics that uniquely influence the pharmacokinetics of delivered drugs. This complexity necessitates innovative solutions to ensure effective drug delivery. Conventional ocular drug administration routes (topical, intravitreal, and systemic) each pose unique limitations. With the advancements of biomaterials science and medical engineering technology, nanofiber hydrogels have garnered significant attention, primarily represented by self\u2010assembled peptide\u2010based hydrogels and cellulose nanofiber\u2010based hydrogels. They can be tailored to have precise physical and chemical properties, enabling controlled release of drugs and enhanced biocompatibility. Furthermore, their nanofibrous structure mimics the extracellular matrix, promoting cell adhesion and tissue regeneration. This review introduces advanced manufacturing techniques which are capable of precisely modifying the properties of nanofiber hydrogels to meet specific therapeutic needs. The distinctive advantages of nanofiber hydrogels are elaborated in detail, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. We also delve into the therapeutic applications, potential limitations, and developmental perspectives of nanofiber hydrogels. Preclinical studies have validated their efficacy in treating ophthalmologic conditions such as age\u2010related macular degeneration, bacterial keratitis, ocular alkali burns, and non\u2010infectious uveitis. However, translating these laboratory findings into clinical applications remains limited, primarily due to significant challenges in human trials, including species\u2010specific responses, the complexity of human biology, and the safety of nanofiber hydrogels. Future refinements in fabrication techniques and rigorous safety assessments are necessary to revolutionize the clinical application of nanofiber hydrogels.<\/jats:p>","DOI":"10.1002\/btm2.70099","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:05:39Z","timestamp":1780567539000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing nanotechnology: Transforming ocular drug delivery with advanced hydrogel systems"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7837-3381","authenticated-orcid":false,"given":"Huidi","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Zhengzhou University Henan Medical College Zhengzhou University School of Medicine  Zhengzhou 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