Biomaterials in Retinal Surgery: Engineering the Future.
Dindar Ismail Ahmed IA, Shoichet Molly S MS, Labriola Jonathan J, Forman Adam A et al.
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. Narrative expert review. Systematic review methodology was not used; no protocol registration, pre-specified eligibility criteria, dual independent screening, or PRISMA flow diagram was undertaken. Published preclinical animal studies, Phase I-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. A structured literature search of PubMed/MEDLINE, supplemented by Google Scholar, was performed from January 2018 to March 2026 across five 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. 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. 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 13.5-25.9 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. 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.