Fabrication of biomimetic corneas featuring epithelial, stromal, and endothelial layers via bioprinting
The bioengineering of full-thickness corneal substitutes presents significant challenges, primarily due to the complex stratified structure of the cornea, which consists of the epithelium, stroma, and endothelium, as well as its critical functional requirements, including optical transparency, mechanical stability, and biocompatibility. Herein, we present an integrated fabrication strategy that combines embedded hydrogel bioprinting with subsequent two-dimensional endothelial cell seeding to create biomimetic corneal structures using a GelMA/HAMA composite hydrogel. The engineered scaffold successfully recapitulates the native cornea's trilaminar architecture (epithelium, stroma, endothelium) and exhibits moderate 30–80% optical transparency across the visible spectrum. The hybrid hydrogel exhibits optimal wettability, a contact angle of approximately 50°, minimal swelling of less than 10%, and controlled degradation kinetics, effectively addressing the limitations of single-component hydrogels. The scaffold maintains structural integrity during suturing and supports robust cellular proliferation and migration. Gene expression analysis reveals the phenotypic orientation of seeded cells toward key corneal lineages, with upregulation of epithelial (KLF4, PAX6), stromal (COL1A1, COL4A4), and endothelial (ZEB1, FOXC1) markers. Overall, the bioprinted GelMA/HAMA biomimetic cornea presents a promising proof of concept for a trilayered tissue-engineered corneal construct.
