Despite significant advancements in hydrogels in recent years, their application in corneal repair remains limited by several challenges, including unfitted curvatures, inferior mechanical properties, and insufficient reactive oxygen species (ROS)-scavenging activities. To address these issues, this study introduces a 3D-printed corneal scaffold with nanocomposite hydrogel consisting of gelatin methacrylate (GelMA), poly (ethylene glycol) diacrylate (PEGDA), Laponite, and dopamine. GelMA and PEGDA act as matrix materials with photo-crosslinking abilities. As a two-dimensional nanoclay, Laponite enhances the rheological properties of the hydrogel, making it suitable for 3D printing. Dopamine self-polymerizes into polydopamine (PDA), providing the hydrogel with ROS-scavenging activity. The incorporation of Laponite and the synergistic effect of PDA endow the hydrogel with good mechanical properties. In vitro investigations demonstrated the cytocompatibility of GelMA-PEGDA-Laponite-dopamine (GPLD) hydrogel and its ROS-scavenging activity. Furthermore, in vivo experiments using a rabbit model of lamellar keratoplasty showed accelerated corneal re-epithelialization and complete stromal repair after the implantation of the 3D-printed scaffold. Overall, due to its high bioactivity and simple preparation, the 3D-printed scaffold using GPLD hydrogel offers an alternative for corneal repair with potential for clinical translation. Statement of Significance: The clinical application of hydrogel corneal scaffolds has been constrained by their inadequate mechanical properties and the complex microenvironment created by elevated levels of reactive oxygen species (ROS) post-transplantation. In this study, we developed a kind of nanocomposite hydrogel by integrating Laponite and dopamine into GelMA and PEGDA. This advanced hydrogel was utilized to 3D print a corneal scaffold with high mechanical strength and ROS-scavenging abilities. When applied to a rabbit model of lamellar keratoplasty, the 3D-printed scaffold enabled complete re-epithelialization of the cornea within a week. Three months after surgery, the corneal stroma was fully repaired, and regeneration of corneal nerve fibers was also observed. This 3D-printed scaffold demonstrated exceptional efficacy in repairing corneal defects with potential for clinical translation.
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