# Biomaterials for Ophthalmic Applications
## 2 Biomaterials in Ophthalmology
### Vitreous Substitutes  
The vitreous body, also called the vitreous or vitreous humor, fills the posterior space of the eye, between the lens and the retina. It occupies more than two thirds of the eye volume. It is a clear gel, highly transparent, inhomogeneous and consists of several parts with different densities and biochemical compositions [12; 13; 89]. The vitreous is composed of water, proteins (mainly collagen), GAG (hyaluronic acid, chondroit sulfate and heparan), metabolites (glucose and lactic acid), ascorbic acid, amino acid, fatty acid, prostaglandin, cells (hyalocytes, fibrocytes/fibroblasts and macrophages) and enzymes [13; 86; 89; 90]. The viscoelastic properties of the vitreous are due to collagen fibers, while the hyaluronic acid provides it with shock-absorbing properties. This protects the structures and tissue of the eye, maintaining the shape of the eyeball and keeping the lens and retina in place [12; 13]. The vitreous has four main functions, which are as follows: a structural function, it supports the eye growth, volume and elasticity; an optical function while maintaining transparency and improving accommodation; a barrier function, forming a barrier to biochemical substances; and a nutritional role in providing nutrients and for metabolism [86]. At birth, the vitreous body is completely gelatinous, with age, the vitreous body gradually liquefies. It is this liquefaction of the vitreous that plays a role in posterior vitreous detachment (PVD), corresponding to vitreous cortex detachment of the retina [13; 89]. An ideal vitreous substitute should be (i) non-toxic and biocompatible with eye tissues, (ii) clear and transparent with a refractive index and density similar to natural glass, (iii) must remain transparent without opacifying after the operation, (iv) an effective buffering agent, (v) allow for the transfer of metabolites, proteins and solutes, (vi) if possible non-absorbable and not biodegradable, (vii) hydrophilic and not soluble in water, (viii) injectable in a small needle, (ix) retain its properties after injection, (x) can be preserved and sterilized without the loss of properties mentioned above. The ideal vitreous substitute does not yet exist and remains a goal to be achieved [13; 89]. The various vitreous substitutes available today make it possible to replace the mechanical role of the vitreous, but they are toxic in the long run. They can be classified into the following broad categories: gas (air, sulfur hexafluoride (SF6)), perfluoropropane (C3F8); liquid (physiological solution, perfluorocarbon fluids (PFCL), semi-fluorinated alkanes (SFA), natural and semi-synthetic polymers namely hyaluronic acid and chitosan, silicone oil; and experimental substitutes. Currently, silicone oil (OS) is the only substance used for long-term vitreous replacement despite some clinical complications [89]. Regarding experimental substitutes, these correspond to the search for a substance with the same molecular structure than the vitreous, as well as the same chemical and physiological properties. These are mainly synthetic polymers, especially hydrogels that can be divided into hydrogels and smart hydrogels. They seem to be promising materials because they have excellent transparency, biocompatibility and can absorb viscoelastic shocks, thus mimicking the behavior of natural vitreous [13]. Hydrogels and smart hydrogels seem to be good candidates as long-term vitreous substitutes once they show excellent transparency and good biocompatibility. They can act as viscoelastic shock-absorbing materials, thereby closely mimicking the behaviour of the natural vitreous body. Hydrogels are networks of polymer chains that contain 99.9% water, they are hydrophilic and not flowable, they swell in aqueous solutions without being solved, can be injected in an aqueous form forming a gel in situ [91]. However, many issues, such as retinal toxicity, increased intraocular pressure, and the formation of opacities still need to be addressed.