Bioengineering the innate vasculature of complex organs: what have we learned so far

Engineering vasculature that meets an organ's specific physiology and function is a fundamental step in organ bioengineering. In this article, we review approaches for engineering functional vasculature for organ bioengineering, with an emphasis on the engineering of organ-specific endothelium and vasculature.

Recent advances in hydrogel-based engineering of vascularized organ bud enable vascular regeneration in self-assembled cellular niche containing parenchymal and stromal cells. The emerging technology of whole-organ decellularization provides scaffold materials that serve as extracellular niche guiding vascular regeneration to recapitulate native organ's vascular anatomy. Increasing morphological and molecular evidences suggest endothelial heterogeneity across different organs and across different vascular compartments within an organ. Deriving organ-specific endothelium from pluripotent stem cells has been shown to be possible by combining endothelial induction with parenchymal differentiation.

Engineering organ-specific vasculature requires the combination of organ-specific endothelium with its unique cellular and extracellular niches. Future investigations are required to further delineate the mechanisms for induction and maintenance of organ-specific vascular phenotypes, and how to incorporate these mechanisms to engineering organ-specific vasculature.