Self-Organization of Long-Lasting Human Endothelial Capillary-like Networks Guided by DLP Bioprinting.

Tissue engineering holds great promise for regenerative medicine, drug discovery and as an alternative to animal models. However, as soon as the dimensions of engineered tissue exceed the diffusion limit of oxygen and nutriments, a necrotic core forms leading to irreversible damage. To overcome this constraint, the establishment of a functional perfusion network is essential. In this work, Digital Light Processing (DLP) Bioprinting was used to encapsulate endothelial progenitor cells (EPCs) in 3D light-cured hydrogel scaffolds to guide them towards vascular network formation. In these scaffolds, EPCs proliferated and self-organized within a few days into branched tubular structures with predefined geometry, forming capillary-like vascular tubes or trees of diameters in the range of 10 to 100 μm. Presenting a confluent monolayer wall of cells strongly connected by tight junctions around a central lumen-like space, these structures could be microinjected with fluorescent dye and were stable for several weeks in vitro. These endothelial structures could be recovered and manipulated in an alginate patch without altering their shape or viability. This approach opens new opportunities for future applications, such as stacking with other cell sheets or multicellular constructs to yield bioengineered tissue with higher complexity and functionality. This article is protected by copyright. All rights reserved.