Biomaterials In Ophthalmology Are Reshaping Ocular Drug Delivery

By Jordana Andrade Santos, Ph.D.

Ophthalmic therapeutics sit at an inflection point. Conventional treatments — eye drops, intravitreal injections, and donor-tissue transplantation — continue to dominate clinical practice despite well-documented shortcomings: bioavailability below 5% for topical formulations, monthly intravitreal injection burden for anti-VEGF therapies, donor cornea shortages, and patient adherence collapse in chronic conditions like glaucoma.^1,2 With over 1 billion people worldwide living with preventable or unaddressed vision impairment, the gap between standard-of-care performance and patient need is widening.¹

Biomaterial-enabled devices, from biodegradable intravitreal implants and drug-eluting punctal plugs to bioengineered corneal scaffolds and nanocarrier platforms, are translating from bench to clinic at an accelerating pace.^2,3 For pharmaceutical developers, CDMOs, and translational scientists, this shift is not merely academic. It is reshaping product life cycle strategy, regulatory pathways, and the competitive landscape for posterior- and anterior-segment therapeutics.

This article examines what the recent literature reveals about biomaterial classes in clinical and preclinical development, the operational and regulatory bottlenecks slowing translation, and where industry investment should focus over the next five years.

Why Ocular Biomaterials Matter Now

The eye is, paradoxically, both an ideal and a hostile environment for drug delivery. The blood-retina barrier limits systemic exposure and its relative immune privilege, particularly in the anterior chamber, allows foreign biomaterials to be tolerated more readily than in most organs. Yet that same anatomy creates formidable pharmacokinetic obstacles: precorneal tear turnover, the multilayered corneal epithelium, the blood-aqueous and blood-retina barriers, and rapid vitreal clearance collectively reduce ocular bioavailability of topically applied drugs to a fraction of the administered dose.²

The clinical consequences are well-rehearsed. Anti-VEGF therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) requires frequent intravitreal injections, historically as many as 13 per year, with attendant risks of endophthalmitis, retinal detachment, and hemorrhage.² Glaucoma management depends on topical regimens with documented adherence rates that collapse in elderly populations. Corneal blindness, which accounts for roughly 12% of global blindness cases, remains constrained by donor tissue availability and graft rejection risk.^3,4

Biomaterials address these failure modes by acting as drug reservoirs, structural scaffolds, regenerative templates, or combinations thereof. The commercial signal is unambiguous: FDA approvals for Ozurdex (dexamethasone PLGA implant), Iluvien (fluocinolone acetonide non-biodegradable implant), Durysta (bimatoprost biodegradable intracameral implant), and Susvimo/Port Delivery System (refillable ranibizumab reservoir) have established biomaterial-enabled devices as a legitimate and reimbursable therapeutic category.³

The Biomaterial Toolbox: What Industry Developers Are Working With

The current development pipeline draws on three broad biomaterial classes, each with distinct CMC, regulatory, and scalability profiles.

Natural polymers, such as collagen, gelatin, silk fibroin, hyaluronic acid, alginate, chitosan, and cellulose, offer intrinsic biocompatibility and, in most cases, biodegradability via well-characterized enzymatic pathways.³

Collagen-based corneal implants developed by Griffith, Fagerholm, and colleagues established the foundational proof of concept for biomaterial-induced corneal regeneration. Their landmark Phase 1 clinical study, published in 2010, demonstrated that cell-free recombinant human collagen implants could stimulate stable, endogenous regeneration of corneal tissue and nerves, with results maintained through 24-month follow-up.⁵ This work catalyzed subsequent platforms, including LiQD Cornea, GelCORE, and GELGYM, and it remains the reference point for regulatory and clinical benchmarking of pro-regenerative corneal biomaterials.¹

Hyaluronic acid also remains a workhorse for injectable hydrogels and viscoelastic surgical adjuncts, and silk fibroin has emerged as a versatile platform for sustained drug release and tissue scaffolding.^2,3

Synthetic polymers, including PLGA, PCL, PLA, PEG, PMMA, polyvinyl alcohol, and more recently polyisobutylene-based copolymers, provide the property tunability that natural materials often lack. They have predictable degradation kinetics, batch-to-batch consistency, and sterilizability without structural compromise and are free of zoonotic pathogen risk. PLGA in particular has become the default chassis for biodegradable intravitreal implants because its hydrolytic degradation profile is well characterized and FDA-familiar.^2,3

Hybrid and bioinspired systems — gelatin methacrylate (GelMA), GELCORE, GELGYM, peptide-based self-assembling matrices, and DNA-inspired Janus base nanotubes — represent the frontier. These platforms aim to combine the bioactivity of natural matrices with the manufacturing reproducibility of synthetic chemistry. Short peptide mimics of full-length proteins are particularly interesting from a CMC standpoint: they can be chemically synthesized at scale, avoid the screening costs associated with animal-derived materials, and offer defined molecular composition that simplifies regulatory submissions.^1,2

Translating Platforms Into Products: Where The Pipeline Stands

Recent clinical trial activity provides a clear view of which biomaterial approaches are gaining traction.

Sustained-release implants dominate the late-stage pipeline. Beyond the approved products noted above, the iDose TR travoprost-eluting intraocular implant has shown 32%–33% reductions in intraocular pressure in Phase 2 studies and is progressing through Phase 3 trials for open-angle glaucoma. OTX-TKI, a PEG hydrogel implant from Ocular Therapeutix, is in clinical evaluation for both AMD and diabetic retinopathy. The IBE-814 non-polymeric implant from Ripple Therapeutics is being assessed in Phase 2 for DME with up to six-months sustained dexamethasone release.²

Reservoir-type refillable devices represent a strategically significant subcategory. The Port Delivery System with ranibizumab, approved in 2021 for treatment of neovascular AMD, eliminates the need for frequent intravitreal injections by allowing transconjunctival refill via a self-sealing septum. The clinical and commercial implications are substantial: a single surgical implantation plus periodic refills can replace what was previously a near-monthly injection cadence, with meaningful consequences for patient quality of life, clinical resource utilization, and payer economics.²

Injectable nanocarriers, hydrogels, liposomes, nanomicelles, dendrimers, and DNA-inspired nanopieces are advancing more variably. Cyclodextrin nanoparticle eye drops for DME have shown Phase 2 efficacy; suprachoroidal triamcinolone acetonide injections (CLS-TA) have completed Phase 2 in combination with aflibercept; and dendrimer platforms such as D-4517.2 are in Phase 2 evaluation for AMD and DME via subcutaneous administration. Janus base nanotubes, while still preclinical, are notable for siRNA delivery applications and have demonstrated superior endosomal escape compared to lipid nanoparticles, a potentially important property for nucleic acid therapeutics targeting retinal disease.²

Bioengineered corneal alternatives, encompassing decellularized xenografts, 3D-bioprinted constructs using decellularized corneal tissue as bioink, and bioadhesive hydrogels, are addressing the donor shortage problem. The pro-regeneration sealant category offers a less costly, immunologically safer alternative to xenogeneic materials and may shift the economics of corneal repair in lower-resource settings.^1,4

Industry Challenges: What Slows Translation

Despite the volume of preclinical literature, the path from laboratory promise to commercial product remains constrained by a recurring set of obstacles:

Manufacturing scalability and CMC consistency. Many high-performing biomaterials, particularly natural polymers and hybrid hydrogels, show limited reproducibility when scaled from bench to GMP manufacturing. Gelatin, despite its low cost and favorable bioactivity, lacks thermostability and typically requires crosslinking strategies that can be difficult to standardize. Decellularized tissue platforms face inherent donor-to-donor variability and synthetic alternatives offer better reproducibility but may trade off bioactivity.³

Sterilization compatibility. Hydrogels are particularly sensitive to terminal sterilization, which can alter network structure, drug release kinetics, and mechanical properties. This is a non-trivial CMC concern that should be addressed early in development, ideally during material selection rather than as an afterthought.²

Degradation kinetics and "burst stage" risk. Biodegradable polymer implants can exhibit uncontrolled terminal release as hydrolysis approaches the critical degradation point. For high-potency molecules, including corticosteroids, prostaglandin analogs, and anti-VEGF biologics, this poses both safety and efficacy concerns. Rigorous characterization across the full degradation profile, not just initial release, is essential.

Regulatory classification ambiguity. Combination products that integrate a sustained-release polymer with an active pharmaceutical ingredient occupy a complex regulatory space. Sponsors must navigate device, drug, and biologic considerations simultaneously, with primary mode of action determining lead center jurisdiction. Early pre-submission engagement with regulators is now a standard best practice.

Safety surveillance over extended timeframes. Ocular implants designed to function for six, 12, or 36 months require correspondingly long safety follow-up. For example, following Ozurdex implantation, ocular hypertension was reported in approximately 27% of recipients in one retrospective series.²

Sustainability and end-of-product-life considerations. Non-biodegradable polymer implants and disposable contact lenses contribute to medical device waste. Industry has historically treated this as peripheral, but regulatory and ESG pressure is rising. Enzymatic degradation pathways and bio-based alternatives are increasingly relevant to commercial positioning.³

Emerging Trends Worth Tracking

Several developments warrant strategic attention from R&D leaders and business development teams.

3D printing and bioprinting of personalized constructs is moving from proof of concept to early clinical exploration, particularly for keratoprosthesis design using decellularized corneal tissue as bioink. The combination of patient-specific imaging, additive manufacturing, and bioactive materials opens the door to true precision ophthalmology.

Stimuli-responsive and self-healing biomaterials, thermosensitive hydrogels that gel at physiological temperature, pH-responsive nanocarriers, and bioadhesive matrices that bond in situ are reducing surgical complexity and enabling office-based or even self-administered procedures.^1,2

Polyisobutylene-based polymers are gaining traction for both intraocular lenses (IOL) and glaucoma microshunts because they resist hydrolysis and oxidation in vivo while triggering minimal foreign body response. This is a meaningful alternative to silicone and acrylic IOL chemistries that have dominated for decades.³

Gene and cell therapy delivery via biomaterial scaffolds, including DNA-inspired Janus base nanotubes for siRNA and mRNA delivery, is positioning biomaterials as enabling technology for the next wave of ocular biologics targeting inherited retinal disease and geographic atrophy.²

Hybrid drug-device combinations, drug-eluting contact lenses, intracanalicular inserts like OTX-TP, and microneedle patches are creating product categories that bridge consumer health, ophthalmic pharmaceuticals, and medical devices.²

Strategic Takeaways For Industry

For pharmaceutical and biotech leadership, the ophthalmic biomaterials landscape offers several actionable insights:

First, life cycle extension through reformulation in a biomaterial chassis is increasingly viable. Established small molecules, including prostaglandin analogs, corticosteroids, and carbonic anhydrase inhibitors, are being repositioned in sustained-release platforms with new IP, new clinical benefit, and new pricing power.²

Second, the anti-VEGF franchise is transitioning from injection-based to device-based delivery, and competitive positioning now requires a clear platform strategy. Companies without a sustained-release road map for posterior segment biologics will face increasing pressure from device-enabled competitors.

Third, CDMOs with specialized capabilities in biomaterial processing, sterile combination product manufacturing, and ophthalmic-grade quality systems are becoming critical strategic partners. Early supply chain engagement is no longer optional.

Fourth, regulatory strategy must be designed from molecule selection forward. The most successful biomaterial-enabled ophthalmic products have benefited from coordinated pre-IND engagement covering chemistry, device design, clinical strategy, and post-market surveillance simultaneously.

Finally, sustainability and biocompatibility are converging as commercial differentiators. Biodegradable, bio-based, and pathogen-free synthetic platforms are positioned to outperform on both clinical and ESG metrics over the next decade.³

The biomaterials revolution in ophthalmology is not a future event; it is a current reality reshaping how ocular disease is treated, how products are developed, and how value is captured. Organizations that align platform strategy, manufacturing capability, and regulatory planning around these technologies will define the competitive landscape through the remainder of this decade.

References:

1. Rodríguez-Lorenzo LM, Reyes-Ortega F, Griffith M. Editorial: Biomaterials used in tissue engineering for the restoration of ocular disorders. Frontiers in Pharmacology. 2024;15:1369505. doi:10.3389/fphar.2024.1369505
2. Sapowadia A, Ghanbariamin D, Zhou L, Zhou Q, Schmidt T, Tamayol A, Chen Y. Biomaterial Drug Delivery Systems for Prominent Ocular Diseases. Pharmaceutics. 2023;15(7):1959. doi:10.3390/pharmaceutics15071959
3. Ramesh D, Wu KY, Kalevar A. Sustainable biomaterials for ophthalmic device engineering: a short review. Biotechnology for Sustainable Materials. 2025;2:15. doi:10.1186/s44316-025-00038-x
4. Chen Z, You J, Liu X, et al. Biomaterials for corneal bioengineering. Biomed Mater. 2018;13(3):032002.
5. Fagerholm P, Lagali NS, Merrett K, Jackson WB, Munger R, Liu Y, et al. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Science Translational Medicine. 2010;2(46):46ra61. doi:10.1126/scitranslmed.3001022

About The Author:

Jordana Andrade Santos, Ph.D., is a toxicologist with a doctoral degree in pharmaceutical sciences and robust experience in regulatory toxicology, non-clinical safety assessment, and the application of new approach methodologies (NAMs). Her expertise spans in vitro and in vivo toxicology, ISO 10993 biological evaluations, CPSR support, and the development of human-relevant models, including 3D cultures and microphysiological systems. She has worked across academia, industry, and consultancy, contributing to regulatory dossiers, R&D programs, and NAM-based innovation for medical devices, cosmetic products, and injectable materials. With international experience in organ-on-chip research at TissUse GmbH in Germany and a background in clinical research coordination, Andrade Santos bridges mechanistic science, regulatory strategy, and translational decision-making in modern safety assessment.