4D bioprinting of self-forming tubular structures for enhanced vascular tissue engineering.

While 3D bioprinting has advanced tissue engineering, the creation of complex, self-supporting structures like hollow tubes has complexities that catalyzed the emergence of 4D bioprinting. Our study introduces a novel approach inspired by nature's ability to create dynamic, hollow structures-such as curling leaves that adapt to environmental conditions through moisture absorption and deswelling. We present a cutting-edge 4D bioprinting method that enables the precise, controlled formation of hollow tubes with varying sizes, utilizing functionally modified silk (namely SilMA) (10-20 %) and its composites (prepared with 0.2-3 % concentrations of carboxy methylcellulose). SilMA and its composites are printed, with parameters such as aspect ratio (less than or equal to 4), crosslinking time (30-60s), and material concentrations adjusted to achieve rapid responsiveness, where structural transformations occur within a minute of external aqueous stimulation. The diameters (700-1000 μm) and shapes of the printed structures (short and long-side morphing) can be controlled with high precision. Our work discusses the effect of composite concentrations on the 4D characteristics of SilMA in detail. While the material and its composites exhibit remarkable swelling behaviour and tensile strength, rivalling that of natural materials, in vitro tests further demonstrate biocompatibility, supporting cell growth, combined with studying the effect of crosslinker concentrations. This study advances the field of vascular tissue engineering. It sets a new benchmark in dynamic material design, showcasing the potential of functionally modified silk in extrusion-based printing and visible-light crosslinking to create adaptable, high-performance structures with rapid response times and customizable configurations.