4D Bioprinting of Self-Morphed Corneal Equivalents Using Smart Hybrid Hydrogels.

Abstract

The curvature of the cornea is intrinsically linked to its topographical features, which are critical determinants of its optical and mechanical performance. While conventional bioprinting enables the fabrication of static, complex geometries, this study introduces a novel 4D bioprinting strategy that allows for the autonomous transformation of flat constructs into anatomically curved shapes, closely mimicking native corneal architecture. By engineering a concentration-dependent swelling gradient in gelatin methacrylate (Gel-MA), controlled, directional folding is achieved through differential cross-linking, enabling spatiotemporally programmed shape morphing. To further enhance architectural precision and structural integrity, geometric patterning is integrated using decellularized corneal matrix (DCM). Despite its resistance to swelling-induced folding, DCM contributed mechanical reinforcement through the printed honeycomb-like microarchitecture. These geometric motifs acted as stress-distributing units, significantly enhancing the construct's ability to withstand physiological forces. Incorporating all of these innovations, a self-curving, multi-material corneal equivalent construct is fabricated by adopting a hybrid architectural strategy, combining material properties with structural organization to create dynamic curvature while preserving mechanical integrity. This work paves the way for a new direction in 4D bioprinting by integrating material gradients, geometric patterning, and shape-programmed design, enabling the replication of complex tissue curvatures without the need for molds or external manipulation.