Vitreoretinal bioadhesives: Translational challenges and innovative perspectives

Bioadhesive materials have been successfully applied across several ophthalmic fields, yet their translation into vitreoretinal surgery for the repair of retinal breaks and defects remains limited. Conventional strategies, including gas and silicone oil tamponade, continue to dominate retinal stabilization; however, they primarily provide temporary cavity-based support rather than direct interfacial closure of retinal defects and may require postoperative positioning, secondary interventions, or carry tamponade-related complications. Despite advances in biomaterial engineering, broader translation of vitreoretinal bioadhesives remains constrained by posterior-segment-specific barriers, including inadequate wet-surface bonding, residual adherent vitreous at retinal break margins, biomechanical mismatch with the compliant neural retina, unfavorable swelling or degradation behavior, inflammatory or proliferative responses, and challenges in precise intraoperative delivery. Importantly, the required adhesive profile differs by indication: peripheral retinal breaks require focal sealing and resistance to fluid ingress and tractional stress, whereas macular holes, optic disc pit maculopathy, and regenerative retinal repair may require different balances of scaffold support, controlled bioactivity, tissue bridging, fibrosis avoidance, and long-term safety. Hydrogel-based vitreous substitutes can reproduce key viscoelastic properties of the native vitreous but remain largely investigational and primarily provide temporary intraocular support rather than direct focal defect repair. Accordingly, next-generation platforms should be designed not simply for adhesion strength, but for indication-specific function, controlled persistence, intraoperative deliverability, secondary-surgery compatibility, and rigorous preclinical and clinical validation. Rather than serving as tamponade replacements, future bioadhesives may be better conceptualized as precision intraocular platforms that complement volumetric tamponade and retinopexy by adding interface-directed defect sealing, biological modulation, and controlled intraocular delivery. This review critically reappraises vitreoretinal bioadhesive strategies, with primary emphasis on retinal detachment and defect repair, through a problem-driven, retina-centered framework that integrates clinical vitreoretinal evidence with adhesion-engineering principles, providing a barrier-oriented translational perspective for interface-directed retinal repair. Building on this analysis, we outline an innovative perspective on the key functional and translational design principles for next-generation vitreoretinal bioadhesives and propose a mechanism-informed roadmap for scalable clinical translation.