ABSTRACT Swelling‐dependent self‐folding hydrogels show considerable promise for tissue engineering applications. However, current systems face limitations in cell growth within the passive layer. This study introduces a novel approach to developing swelling‐dependent bilayer hydrogels using biocompatible and biodegradable composites of methacrylated silk fibroin and methacrylated gelatin (SilMA‐GelMA) through a “sonication‐photocrosslinking” strategy. The sonication treatment induces beta‐sheets (β‐sheets) formation in silk fibroin molecules, creating a stable, less swellable passive layer while maintaining material consistency across the bilayer structure. Comprehensive characterization revealed significant differences in swelling ratio, mechanical properties, and degradation profiles between sonicated and nonsonicated layers. The optimized bilayer hydrogel composed of 50% GelMA with 50% SilMA (GS5) as the active layer and sonicated GS5 (GSS5) as the passive layer demonstrated efficient self‐folding behavior, forming complete tubular structures after incubation. Furthermore, cell encapsulation experiments with human umbilical vein endothelial cells (HUVECs) revealed high cellular viability and proliferation in both sonicated and nonsonicated hydrogel layers over a 5‐day culture period. This biocompatible and biodegradable swelling‐dependent self‐folding hydrogel provides a promising platform for creating complex, cell‐laden tissue engineering constructs with controlled spatial distribution of cells and is particularly suitable for tubular tissue applications such as vascular engineering and the formation of other hollow organ structures where precisely controlled cellular organization is essential for proper function.
Xiao et al. (Thu,) studied this question.