Matrix Viscoelasticity Controls Differentiation of Human Blood Vessel Organoids into Arterioles and Promotes Neovascularization in Myocardial Infarction

• DOI: 10.1002/adma.202410802
• Publication Date: 2024-12-17T08:37:43Z
• Authors: Dayu Sun; Kunyu Zhang; Feiyang Zheng; Guanyuan Yang; Mingcan Yang; Youqian Xu; Yinhua Qin; Mingxin Lin; Yanzhao Li; Ju Tan; Qiyu Li; Xiaohang Qu; Gang Li; Liming Bian; Chuhong Zhu
• Keywords: Organoid; Regenerative Medicine

Stem cell-derived blood vessel organoids are embedded in extracellular matrices to stimulate sprouting. Although vascular 3D collagen I-Matrigel gels currently available, they primarily capillaries composed of endothelial cells (ECs), pericytes, and mesenchymal stem-like cells, which necessitate mature arteriole differentiation for neovascularization. In this context, the hypothesis that matrix viscoelasticity regulates development is investigated cultures by encapsulating within viscoelastic gelatin/β-CD assembly dynamic hydrogels or methacryloyl gelatin non-dynamic hydrogels. The hydrogel demonstrate enhanced angiogenesis into arterioles containing smooth muscle cells. mechanical microenvironment promotes patterning arteriolar elevating notch receptor 3 signaling stem downregulating platelet-derived growth factor B expression ECs. Transplantation vivo, along with hydrogel, leads reassembly restoration cardiac function infarcted hearts. These findings indicate properties play a crucial role controlling organization processes, suggesting an exciting potential its application regenerative medicine.