Injectable double-network hydrogel for corneal repair

Abstract

Injuries to the cornea can cause corneal opacity or even blindness. Especially scald wounds and chemical burns to the cornea can usually lead to loss of corneal epithelium function and deep damage to the corneal stroma. Injectable hydrogel has been widely applied in corneal tissue engineering because it is easy to handle and can completely fill the defect area with minimally invasive surgical procedures. To reduce the risk and complications of penetrating keratoplasty and lamellar keratoplasty and to meet the demand for donated cornea, an injectable double-network (IDN) hydrogel based on methacrylated gelatin (Gel-MA) and oxidized hyaluronic acid (OHA) was constructed for focal corneal defect repairing. The Gel-MA/OHA IDN hydrogel had an interconnected porous microstructure and tunable mechanical properties with a modulus between 3.4 and 176.4 kPa. The hydrogel could promote cell adhesion and proliferation and afford the sustained release of hydrophilic/hydrophobic drugs. In-vivo corneal repair was performed by injecting the precursors into the pre-drilled epithelial-stromal defects of New Zealand White rabbits followed by immediate in-situ UV crosslinking. The results showed that the hydrogel had a strong capacity to promote corneal regeneration. Optical coherence tomography, slip lamp, fluorescein staining, scanning electron microscopy (SEM), and haematoxylin & eosin (H&E) staining were employed to illustrate the effectiveness and safety of corneal tissue regeneration. All the results showed that the optimized Gel-MA/OHA IDN hydrogel possessed excellent biocompatibility and could promote cornea repair in vivo. This study suggests that the injectable biocompatible double network hydrogel may provide a good choice for corneal repair and regeneration.