Research highlights Cole A . DeForest , a

Mass transport within native human tissue enables delivery of nutrients to and removal of waste from cells embedded in a dense 3D matrix material. Blood flow through cardiovascular networks (e.g., veins and arteries) provides nutrients that can diffuse into the tissue. The ability to deliver nutrients deeper into the tissues is a critical issue in the development of large-scale multicellular organisms. As researchers attempt to regrow and recreate tissue-like structures, they face a major challenge in engineering an efficient vasculature. The desired vasculature is expected to promote cell survival within thick tissue constructs, where bulk diffusion is insufficient in supporting basic function. Recently, Chen and colleagues have introduced an elegant and effective solution that utilizes simple sugars to create desired vasculature within synthetic tissues. In their work, carbohydrate glass was extruded with a custom-modified 3D printer to generate open solid lattice networks. This self-supporting structure was then encapsulated inside cell-laden hydrogels, which mimicked the native extracellular matrix (ECM). As the carbohydrate glass rapidly dissolved in water and cell media, liberating only fully cytocompatible sugar monomers (e.g., sucrose, glucose), the user was left with a scaffold with hollow channels that is akin to the native vasculature (Fig. 1). These microscale channels could then be perfused with nutrients to promote the survival and function of the encapsulated cells. Utilizing carbohydrate glass as a sacrificial material has many advantages from a fabrication standpoint. First, the degradation products of the carbohydrate glass are cytocompatible. Next, the diameter of the printed filaments can be readily controlled by varying the translational velocity of the extrusion nozzle. This yields structures with diameters similar to those of human blood vessels. Additionally, the sugar mixture is capable of physically supporting its own weight, allowing for complex interconnected structures to be printed via standard 3D printing techniques. Finally, the material is optically clear and transparent to light wavelengths that enable cellular imaging, fluorescence microscopy, and photopolymerization. Upon infusing human umbilical vein endothelial cells (HUVECs) into the hollow microchannels of the hydrogel, uniform cell seeding along the channel walls and generation of key vascular components was observed. HUVECs lined the cylindrical walls, resulting in a lumen structure required for nutrient perfusion. Spontaneous sprouting of new vessels, one of the holy grails of vascular tissue engineering, was observed from the vein-like structures and into the bulk hydrogel. Furthermore, encapsulated cells uniformly distributed throughout the synthetic ECM exhibited increased viability and function within hydrogel constructs containing perfusion channels, owing to the increased nutrient availability deep within the material construct. By combining emerging 3D printing techniques with established tissue engineering approaches, Miller et al. have made a major stride in the creation of synthetic cardiovascular structures. The proposed approach is highly versatile, compatible with a variety of cell types and synthetic ECM mimics, and should prove successful in the engineering of thick tissues for applications in regenerative medicine.