Magnetically assembled endothelial cell-coated spheroid for vascularization

3D spheroids are used as a therapeutic strategy and transplanted in vivo owing to their ability to better mimic the microphysiological environment that is crucial for the transplants to be able to engraft and vascularize for their long-term survival and functionalization in the host tissue. Among various methods of fabricating spheroids, the utilization of magnetic force enables rapid cell aggregation and spatial regulation. Encapsulating a magnetic spheroid with endothelial cells paves the way toward vascularization. Here, we magnetically bioprinted vascular assembly by coating magnetic spheroids with the magnetic nanoparticles (MNPs)-internalized vascular endothelial cells. MNPs-internalized mouse myoblasts cells (C2C12) were magnetically aggregated by placing a neodymium magnet under a well plate and then encapsulated by MNPs-internalized human umbilical vein endothelial cells (HUVECs). Internalization of MNPs did not hinder cell viability and vascularization-related gene expression, and the transplant of the vascular assemblies could sprout and be engrafted into the host tissue within three days. As these vascular assemblies are easily fabricated by coating spheroids with MNPs-internalized endothelial cells and controlled by a magnetic force, they may be used for engraftment and vascularization in various applications with spheroids with different functions.