Bio-Inspired Design of 4D-Printed Scaffolds Capable of Programmable Multi-Step Transformations Toward Vascular Reconstruction

Many withered leaves or flowers spontaneously curl and transform from flattened structures into tubular constructs upon dehydration. Inspired by this phenomenon, an innovative strategy is developed to design stimuli-responsive scaffolds that are capable of programmable transformation from flattened 2D constructs into various curled 3D tissue-mimicking structures. Specifically, Janus-structured scaffolds consisting of a passive layer of polycaprolactone and an active, triggered-transforming layer of methacrylate gelatin/alginate hydrogel are 3D-printed, which replicate the asymmetrical structure of leaves and enabled on-demand transformation into desired curvatures and shapes through mimicking the regulation mechanism of leaves curling behavior by mesophyll matrix stiffness and vein patterns. Particularly for vascular reconstruction, multi-step transformation scaffolds capable of primary 2D-to-3D transformation into tubular constructs induced by dehydration, and secondary transformation to adapt to the local intravascular geometry in vivo, are successfully developed. In addition, the oriented polycaprolactone layer of the printed scaffold can enable the adhesion, proliferation, and orientation of endothelial cells, thus demonstrating a novel strategy for the design of tissue-engineered blood vessels. In general, this study provides an innovative design strategy for programmable biomaterials capable of shape morphing and adaptation in physiological conditions, thereby opening up a new avenue for the design of intelligent biomaterials in regenerative medicine. This work proposes an innovative biomimetic design strategy for 4D printing of stimulus-responsive Janus scaffolds that are capable of programmable multi-step transformations towards vascular reconstruction. By mimicking the regulation mechanism of mesophyll matrix stiffness on curling curvature and vein pattern on curling direction to tailor the contraction mismatch between the two layers, thus can design and obtain tissue-mimicking structure. image