Toward the ideal corneal construct: Design principles, biofabrication strategies, and translational challenges in 3D...

Corneal blindness affects millions worldwide, yet donor tissue remains insufficient to meet clinical demand. In this context, 3D bioprinting has emerged as a promising approach for fabricating corneal constructs with controlled architecture and composition. This review examines recent advances in corneal tissue engineering, focusing on bioink design, biofabrication strategies, and functional characterization, and emphasizing the parameters required to achieve optical transparency, mechanical stability, and biological performance. Particular attention is given to the relationship between bioink composition, printability, and post-fabrication behavior, highlighting how these factors collectively determine construct functionality. The review also discusses emerging technologies, including dynamic biomaterials, advanced biofabrication techniques, and data-driven approaches, that are expanding the design space of corneal constructs. In addition, current strategies for implantation and in vivo evaluation are evaluated for their clinical applicability. A critical assessment of the field is presented, addressing both the potential of engineered corneal constructs and the technical and translational challenges that limit their clinical implementation, including reproducibility, scalability, long-term integration, and regulatory considerations. Finally, future directions are outlined, with emphasis on integrating automated manufacturing systems and artificial intelligence to improve design, standardization, and translational efficiency. Overall, 3D bioprinting provides a framework for developing functionally relevant corneal substitutes, supporting both therapeutic applications and advanced in vitro research and drug testing models.