Hydrogel-Based Vitreous Substitutes

Abstract

Hydrogel-based vitreous substitutes have been considered as a potential solution for the treatment of retinal disorders, especially when the natural vitreous body is damaged due to trauma, disease, or surgery. With their high-water content, biocompatibility, and tunable mechanical properties, these hydrogels offer a promising alternative to traditional vitreous substitutes. This review explores the role of polymers and crosslinkers in the development of hydrogel-based substitutes, focusing on how these components contribute to the structure and function of hydrogels. The choice of natural polymers, such as hyaluronic acid and collagen, or synthetic ones, such as polyethylene glycol and polyvinyl alcohol, is crucial to mimic the transparency and flexibility of the vitreous body. Crosslinking methods, including physical, chemical, and enzymatic approaches, help control the gelation process and enhance the mechanical strength of the hydrogel. Furthermore, this review demonstrates how these hydrogels interact with biological tissues, which enhances biocompatibility, cell growth, and tissue repair. This review also discusses the challenges and future directions in improving these hydrogels, particularly in terms of long-term stability, integration with ocular tissues, and appropriate mechanical properties. Overall, hydrogel-based vitreous substitutes have significant potential to improve surgical outcomes and restore vision for patients with vitreous injury.

Keywords: crosslinking strategies; polymeric hydrogel; vitreous substitutes.

Figure 1

Suitable polymers for the fabrication of injectable hydrogel-based vitreous substitutes.

Figure 2

Illustration of natural-polymer-based hydrogel as a vitreous substitute: (A) SH-HA synthesis scheme, (B) schematic of HA-BDDE crosslinked hydrogel as a vitreous replacement, (C) injectable hydrogel based on water-soluble chitosan and hyaluronic acid for a vitreous substitute, and (D) in situ alginate-phenylboronic acid/polyvinyl alcohol composite hydrogel (TALPPH) as a potential vitreous substitute with a tamponading function.

Figure 3

Illustration of various crosslinking strategies in hydrogel design via physicochemical crosslinking methods.

Figure 4

Diagram of the vitreous constituent parts in the human eye.

Figure 5

Schematic of the Kelvin–Voigt model illustrating hyaluronic acid’s viscoelastic behavior, with a spring for elasticity and a dashpot for viscosity. Internal pressure (IOP) applies to the force. Adapted from Figure 1 of [104].

Figure 6

Effect of aging on different hydrogels for vitreous hydrogel substitutes. Dark lines are before, and red lines are after aging for (A) Densiron, (B) Siluron 5000, (C) Albomed HA, and (D) alginate 0.5%. Also, it is worth noting that these diagrams represent the elastic modulus numbers in Pa. As is clear after aging, the elastic modulus is increased, so this will result in greater stiffness, which could cause the pressure in the eye to rise [100].