Vascularization in Engineered Tissue Construct by Assembly of Cellular Patterned Micromodules and Degradable Microspheres

Tissue engineering aims to generate functional tissue constructs in which proper extracellular matrix (ECM) for cell survival and establishment of a vascular network are necessary. A modular approach via the assembly of modules mimicking the complex tissues' microarchitectural features and establishing a vascular network represents a promising strategy for fabricating larger and more complex tissue constructs. Herein, as a model for this modular tissue engineering, engineered bone-like constructs were developed by self-assembly of osteon-like modules and fast degradable gelatin microspheres. The collagen microspheres acting as osteon-like modules were developed by seeding human umbilical vein endothelial cells (HUVECs) onto collagen microspheres laden with human osteoblast-like cells (MG63) and collagenase. Both HUVECs and MG63 cells were well spatially patterned in the modules, and collagen as ECM well supported cell adhesion, spreading, and functional expression due to its native RGD domains and enzymatic degradation activity. The patterned modules facilitated both the cellular function expression of osteogenic MG63 cells and vasculogenic HUVECs; that is, the osteon-like units were successfully achieved. The assembly of the osteon-like modules and fast degradable gelatin microspheres promoted the vascularization, thus facilitating the osteogenic function expression. The study provides a highly efficient approach to engineering complex 3D tissues with micropatterned cell types and interconnected channels.