Advanced 3D scaffolds for corneal stroma regeneration: a preclinical progress

Corneal stromal defects represent a significant global cause of blindness, necessitating innovative therapeutic strategies to address the limitations of conventional treatments, such as corneal transplantation. Tissue engineering, a cornerstone of regenerative medicine, offers a transformative approach by leveraging biomaterial-based solutions to restore damaged tissues. Among these, three-dimensional (3D) scaffolds fabricated using advanced techniques like 3D printing have emerged as a promising platform for corneal regeneration. These scaffolds replicate the native extracellular matrix (ECM) architecture, providing a biomimetic microenvironment that supports cell proliferation, differentiation, and tissue integration. This review highlights recent advances in the design and fabrication of 3D scaffolds for corneal stroma engineering (CSE), emphasizing the critical interplay between scaffold architecture, mechanical properties, and bioactive signaling in directing cellular behavior and tissue regeneration. Likewise, we emphasize the diverse range of biomaterials utilized in scaffold fabrication, highlighting their influence on cellular interactions and tissue reconstruction. By elucidating the complex relationship between scaffold design and biologics, this review aims to illuminate the evolution of next-generation strategies for engineering functional corneal tissue. Eventually, this review will provide a comprehensive synthesis of the current state-of-the-art in 3D scaffold-based corneal tissue engineering (CTE), offering insights that could advance progress toward effective vision restoration therapies.