Abstract 5862: Tissue Engineering of Living Small-Diameter Vascular Grafts: A Novel Concept Based Exclusively on Self-Assembled Microtissue Building Blocks
Introduction Current state-of-the-art technologies to generate tissue engineered blood vessels (TEBV) comprise scaffold-based concepts or wrapping of cell sheets to shape tubular constructs. Both approaches show limitations, preventing routine clinical use. Here, a novel concept to create small diameter TEBV based exclusively on microtissue (MT) self-assembly (living cellular re-aggregates), incorporating endothelial cells to enable the development of a vaso vasorum is presented.
Materials and Methods A novel bioreactor was designed to assemble MTs in a vascular shape and apply flow and mechanical stimulation. MTs composed of human artery-derived myofibroblasts (MF) and endothelial cells (HUVEC) were accumulated (3mm in diameter, 1mm wall thickness) and cultured for 7 and 14 days under pulsatile flow or static culture conditions. The resulting vessels were analyzed by immunohistochemistry for extracellular matrix and cell phenotype (vWF, a-SMA, Ki67, VEGF).
Results Self-assembled MTs displayed significantly accelerated ECM formation compared to monolayer cell sheets. Accumulation to vessel-like tissue occurred within 14 days under both, static and flow/mechanical stimulation conditions. A layered tissue formation was observed only in the flow group, as indicated by luminal aligned a-SMA positive MF. Endothelial cells were detected throughout the vessel wall.
Conclusions It is demonstrated that self-assembled MTs can be used as building blocks to generate living small diameter TEBV. Significantly accelerated ECM maturation, prevascularization capacity and avoiding foreign material makes this approach highly attractive to generate TEBV.