The eye is a highly specialized optical and mechanical system whose structural integrity and visual performance rely heavily on the precise arrangement of the extracellular matrix (ECM). As the primary structural protein of the ocular ECM, collagen provides not only physical support through its hierarchical self-assembled structure but also regulates cellular behavior via bioactive sequences. However, bridging the gap from natural tissues to synthetic biological scaffolds to achieve precise emulation of the complex microenvironments in the cornea, sclera, and retina remains a core challenge in ocular tissue engineering.

Previous research predominantly focused on the biocompatibility of collagen as a single substrate, lacking systemic exploration into its hierarchical structure, cross-linking kinetics, and biomechanical adaptability at specific anatomical sites. This limited research paradigm made it difficult for synthetic materials to fully restore the high degree of order and long-term stability characteristic of natural tissues.

The review article titled “Ocular collagen: From architecture to biomaterials,” published in Eye Discovery (2026) by researchers from East China University of Science and Technology, systematically evaluates the distribution logic of collagen across various ocular tissues. It discusses cutting-edge progress in constructing high-performance ophthalmic repair materials using physical, chemical, and biological methodologies.

In-depth Analysis: Hierarchical Design and Functional Fabrication of Collagen

1. Structural Organization and Physiological Significance of Collagen: As the principal structural protein of the ocular extracellular matrix, collagen forms hierarchical assemblies from triple-helical molecules to fibrils and higher-order networks, providing the mechanical framework required for tissue integrity and function. At the same time, collagen regulates cell adhesion, migration, proliferation, and differentiation through integrin-mediated interactions. Its highly specialized distribution in the cornea, retina, sclera, conjunctiva, and eyelids enables distinct optical, barrier, protective, and biomechanical functions, making it indispensable for ocular homeostasis, repair, and regeneration.

2. Fabrication of Collagen into Diverse Biomaterial Forms: Another major advantage of collagen lies in its versatile processability. Through techniques such as 3D printing, electrospinning, electrodeposition, and in-situ injection, collagen can be engineered into hydrogels, films, fibres, scaffolds, and injectable systems for ophthalmic use. These approaches enable control over fibril alignment, porosity, geometry, and local morphology, allowing collagen-based materials to better match the structural and mechanical requirements of different ocular tissues. In this way, collagen serves as a highly adaptable platform linking molecular design with advanced manufacturing.

3. Extensive Applications in Ophthalmic Repair: Building on its structural relevance and engineering flexibility, collagen has been widely explored across multiple ocular applications. In the cornea, it is used in substitutes and bandage lenses; in the retina and choroid, it supports cell carriers, drug-delivery systems, and Bruch’s membrane analogs; and in the ocular surface and adnexa, it contributes to conjunctival reconstruction, eyelid repair, scleral reinforcement, glaucoma surgery, and lacrimal duct repair. These advances highlight collagen’s transition from a replacement material to a platform for functional ocular regeneration.

Scientific Significance and Clinical Application Trends

By correlating collagen molecular conformation with processing techniques, this review outlines a translational path from basic protein science to high-performance clinical medical devices. This evolution involves the multi-dimensional intersection of materials science, polymer physics, and ophthalmic pathology.

The study concludes that collagen, with its high processability, excellent biocompatibility, and customizable degradation profiles, has become the preferred substrate for ocular regenerative medicine. Future research will focus on developing intelligent collagen scaffolds with spatio-temporal responsiveness and overcoming the mechanical deficiencies of single components through multi-material composites, such as hybridizing collagen with synthetic polymers. These advancements not only provide engineered solutions for the shortage of corneal donors but also offer core support for developing complex ophthalmic implants like glaucoma drainage systems and retinal repair bases.