One-Step Coordinated Multi-Kinetic 4D Printing of Human Vascularized Cardiac Tissues with Selective Fast-Shrinking Capillaries.

Abstract

The field of 3D bioprinting has made substantial progress in recent years, enabling the fabrication of vascular networks within engineered tissues to support the efficient transfer of oxygen and nutrients. However, a critical limitation remains: the restricted resolution of cell-laden bioink hydrogels, which impedes the precise formation of microscale structures such as capillaries. In this study, a novel, sequential, one-step bioprinting approach is introduced that enables the deposition of multiple cell-laden bioinks, facilitating the fabrication of functional, complex cardiac tissues with hierarchical microvasculature. Remarkably, this strategy enables pre-designed blood vessels to undergo selective shrinkage to capillary-scale dimensions within the parenchymal tissue under physiological conditions. Engineered cardiac tissues with perfusable, endothelialized vascular networks exhibit robust contractile function, and in vivo implantation demonstrate successful anastomosis of the vasculature with the host. This bioprinting strategy represents a significant advancement in the engineering of physiologically relevant tissue architectures, paving the way for the development of functional organotypic constructs for regenerative medicine and transplantation.