Human Corneal Lenticules Decorated with Mesenchymal-Stem-Cells-Encapsulated Microneedles for Cornea Stroma Regeneration

Human corneal stromal lenticules obtained from refractive surgeries have merged as a promising alternative for corneal regeneration, although their applications face challenges such as rejection reactions, inflammatory responses, and graft instability. To overcome these challenges, we developed decellularized human stromal lenticules integrated with microneedles, designed as a delivery matrix for mesenchymal stem cells (MSCs) to facilitate corneal regeneration. The microneedle patches consist of MSC-encapsulated methacrylated hyaluronic acid (HAMA) hydrogel needle tips with a corneal lenticule-based supporting substrate. Following decellularization, the corneal lenticules could retain transparency and structural integrity, while the microneedle structure exhibited favorable mechanical properties for minimal-invasive implantation and stabilization within local defects. The MSCs-encapsulated tips exhibit high cell viability at optimized hydrogel concentration and polymerization time, promoting the secretion of various bioactive substances that enhance cell migration and proliferation and alleviate oxidative stress in vitro. In rabbit keratoplasty evaluations, the implanted lenticules remained transparent, which accelerated healing and restored the corneal volume. Furthermore, the implanted intrastromal area exhibited reduced fibrosis, increased extracellular matrix deposition, and good biocompatibility with the host corneas in vivo. These results indicated that our corneal stromal lenticules decorated with MSCs-encapsulated microneedles served as an effective transplant graft, offering significant clinical potentials for corneal regeneration.