3D printing of stiff, tough, and ROS-scavenging nanocomposite hydrogel scaffold for in situ corneal repair

Abstract

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 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 one 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.