Ocular collagen: From architecture to biomaterials

Ocular tissues have a complex architecture and present significant challenges for repair. Collagen, due to its structural and compositional similarity to the ocular extracellular matrix and its versatile processability, is widely used as a scaffold. This review discusses the structure and fabrication of collagen, its resemblance to ocular tissues, and its application in ophthalmic research and therapy. First, we describe the molecular structure of collagen, its self-assembly, and its distribution in ocular tissues, including the cornea, retina, and sclera. We also review fabrication techniques such as 3D printing, electrospinning, electrodeposition, and in-situ injection. Next, we examine applications by tissue type. For the cornea, these include corneal substitutes, bandage lenses, and in situ crosslinking. For the retina and choroid, applications include cell carriers, drug delivery systems, and Bruch’s membrane analogs. For the ocular surface, collagen is used in conjunctival reconstruction, eyelid repair, scleral reinforcement, as an adjunct in glaucoma surgery, and in lacrimal duct repair. Finally, we discuss the challenges associated with collagen use, including source safety and batch variability, the interrelation of crosslinking, mechanical properties, degradation, and transparency, accurate replication of three-dimensional structure and anisotropy, the cost and stability of recombinant human collagen, and issues of adulteration and regulatory gaps. We propose that multiscale, bioinspired design combined with advanced manufacturing strategies could enable transition from structural replacement to functional regeneration, thereby accelerating clinical translation.