Lego-Inspired Splicing of Modularized Vascular Channels

Vascular channels embedded within tissue-engineered hydrogels play a crucial role in replicating natural physiological environments and facilitating the delivery of nutrients and removal of metabolic byproducts. Although present techniques provide diverse strategies to create vascular channels, the flexible and scalable construction of these channels within hydrogels remains a challenge. Here, inspired by Lego assembly, an innovative modular construction strategy is introduced for developing perfusable vascular channels within hydrogels. This approach involves the customized design and fabrication of individual modules featuring diverse vascular channel architectures, which can be flexibly assembled into large-scale hydrogel constructs with hierarchical vascular channels through splicing. As a proof of concept, gelatin-based constructs with vascular channels are spliced across multiple dimensions-1D, 2D, and 3D-to validate the flexibility and scalability of the splicing technique. These vascular hydrogel constructs are successfully perfused, and the interfacial strengths of the different spliced constructs are characterized. Furthermore, a functionalized construct capable of mimicking the vascular barrier function of human umbilical vein endothelial cells (HUVECs) is established, and determined arterial endothelial cell integrity and functionality under flow conditions. The innovative splicing technique offers new insights into the construction of large-scale in vitro vascularized tissues, paving the way for addressing specific tissue engineering needs.