Angiogenesis induction using organoid-tissue modules: A platform for modular vessel construction

Abstract

Angiogenesis is essential for successful tissue regeneration, particularly in clinical contexts such as ischemic injury, wound healing, and reconstructive therapies. However, the establishment of functional vasculature remains a major limitation in organoid-based systems. In this study, we developed vascularized organoid tissue modules (Angio-TMs) by incorporating human umbilical vein endothelial cells (HUVECs) into scaffold-free, self-organized constructs. Remarkably, the inclusion of HUVECs at 1% of the total cell population was sufficient to generate highly reproducible and structurally stable Angio-TMs, which exhibited clear endothelial differentiation and vascular functionality both in vitro and in vivo. Furthermore, inhibition of transforming growth factor (TGF)-β signaling in Angio-TMs led to a 2.5-fold increase in vessel length density, demonstrating a substantial enhancement in angiogenic potential. These findings highlight Angio-TMs as a robust and modular platform for engineering vascularized tissues and underscore their translational relevance in regenerative medicine and tissue transplantation.