3D-Bioprinted Biomimetic Epithelial-Stromal Hydrogel Construct with In Situ Photocrosslinkable Bioadhesive for Suture-Free Corneal Regeneration.

Abstract

3D bioprinted corneal equivalents can faithfully replicate native tissue architecture, but their clinical translation has been hindered by the reliance on traumatic suturing techniques. To address this challenge, we developed an integrated bioadhesive strategy for suture-free transplantation of biomimetic corneal constructs. Using digital light processing (DLP), we fabricated an epithelial-stromal bilayer scaffold with spatially organized corneal epithelial cells (CECs) and corneal stromal stem cells (CSSCs) in their respective layers through photopolymerization of gelatin methacryloyl (GelMA)/2-aminoethyl methacrylated chondroitin sulfate (CSAMA) bioinks. Critically, N-hydroxysuccinimide-modified chondroitin sulfate methacrylate (CSMA-NHS) was synthesized, and GelMA-CSMA-NHS bioadhesive achieved in situ anchoring of 3D bioprinted scaffolds to the corneal stroma through synergistic topological adhesion and amide-bonding. The rabbit anterior lamellar keratoplasty model demonstrated that this combination strategy can achieve in situ corneal defect closure and effectively promote corneal re-epithelialization and stromal regeneration, reducing corneal scar formation. This integrated strategy combines 3D bioprinting with in situ adhesion to simultaneously reconstruct the corneal multilayered architecture and enable suture-free implantation, presenting a promising approach for corneal repair.