American Journal of Ophthalmology

Biomaterials in Retinal Surgery: Engineering the Future

Experiments in animalsInterventions
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Abstract

PURPOSE: To review current and emerging biomaterials in retinal surgery-vitreous tamponade agents, retinal prostheses, retinal pigment epithelium (RPE) transplant scaffolds, intraocular drug delivery platforms, and gene therapy vectors-with emphasis on the authors' oxime-crosslinked hyaluronic acid vitreous substitute. DESIGN: Narrative expert review. Systematic review methodology was not used; no protocol registration, prespecified eligibility criteria, dual independent screening, or PRISMA flow diagram was undertaken. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Published preclinical animal studies, Phase I to III clinical trials, US Food and Drug Administration approvals, and real-world evidence on biomaterials in posterior segment surgery. No individual patient data were accessed. METHODS, INTERVENTION, OR TESTING: A structured literature search of PubMed/MEDLINE, supplemented by Google Scholar, was performed from January 2018 to March 2026 across 5 domains: vitreous tamponade agents; retinal prostheses; scaffold-based RPE transplantation; nanoparticle and sustained-release drug delivery; and gene therapy vectors. Peer-reviewed investigations, trial reports, and regulatory data were prioritized. The authors' preclinical hydrogel data are presented as original data within a review context. MAIN OUTCOME MEASURES: Best-corrected visual acuity, intraocular pressure, electroretinography, retinal microstructure on optical coherence tomography, prosthetic visual acuity, ellipsoid zone area loss, injection frequency, and in vivo biocompatibility. RESULTS: The PRIMA photovoltaic subretinal implant produced a clinically meaningful improvement in visual acuity in 26 of 32 patients (81%) with geographic atrophy at 12 months. A 44-channel suprachoroidal prosthesis showed no device-related serious adverse events at 2.7 years. The authors' oxime-crosslinked hyaluronic acid hydrogel demonstrated density 1.01 g/mL and refractive index 1.356, with preserved electroretinography and intraocular pressure of 13.5 to 25.9 mmHg in rabbits. Scaffold-based RPE transplantation has entered Phase I/IIa trials. 2025 approvals included a refillable ranibizumab port delivery system for diabetic retinopathy and the first encapsulated cell therapy implant for macular telangiectasia type 2. Three Phase 3 anti-VEGF gene therapy trials are ongoing. CONCLUSIONS: Biomaterial engineering is transforming retinal disease management from stabilization toward tissue replacement and vision restoration. Principal limitations are the preclinical status of the hydrogel data and early-phase status of RPE scaffold trials. Outstanding challenges include long-term in vivo stability, immunological management of allogeneic constructs, scalable manufacturing, and definitive efficacy trials.