Biofabrication of Hierarchical Medium-Sized Branched Blood Vessel Scaffolds Utilising Negative Embodied Sacrificial...

This study develops 3D-printed hollow structures for tissue engineering purposes, with particular focus on the development of branched hierarchical medium-sized blood vessels in the 1-2 mm diameter range. Hierarchical medium-sized branched blood vessels that link an incorporated capillary network within engineered tissues to the larger vessels of the systemic circulation, providing an immediate blood supply to thick tissues, underlie the development of large tissue-engineered organs, but are currently unavailable in tissue engineering. Using a modified version of the injection molding technique, Negative Embodied Sacrificial Template 3D (NEST3D), we demonstrate the biofabrication of 3D structures that are both branched and hollow. The technique is scalable; hollow structures with outer diameters of 0.5 to 20 mm and 20 to 150 mm in length can be created. The technique is compatible with various biomaterials, namely, gelatin, poly-caprolactone, and silicone PDMS. Human-induced pluripotent stem cells differentiated into vascular cell types are a valuable cell source for personalized medicine. This study demonstrates that NEST3D-generated medium-sized (0.88-1.3 mm inner diameter) branched structures could be seeded with endothelial or vascular smooth muscle cells derived from human-induced pluripotent stem cells, with these cells attaching to the inner surface of the branched vessels. In the future, applications such as biofabrication of personalized blood vessels, connecting with incorporated capillary networks for in vivo implantation or in vitro tissue models, may benefit from this new technology.