Effect of Extracellular Matrix Density and Cell Number on Blood Capillary Formation in Three-Dimensional Tissue

Abstract The construction of three-dimensional (3D) capillary tissue is still a central issue in the field of tissue engineering. To improve the vascularization of 3D tissue, elements including growth factors and scaffold type have been found to affect the construction of 3D capillary structures. However, the effect of other factors such as modulus or cell number on blood capillaries remains unclear. In this work, a high-throughput 3D-human blood capillary model was fabricated via sedimentary culture method, based on 3D culture of endothelial cells and fibroblasts with the support of collagen microfibers (CMFs) as an extracellular matrix. The amount of CMF or cell number was varied to evaluate the relationship between tissue modulus and blood capillary length. Although varying the amount of CMF did not significantly affect these factors, the numbers of fibroblasts and endothelial cells indicated a huge impact on the modulus of tissues and the length of blood capillaries. These findings provide an important basic knowledge of blood capillary formation in 3D tissue in the field of 3D tissue engineering.