Human Microvasculature Fabrication Using Thermal Inkjet Printing Technology

Abstract

The current tissue engineering paradigm is that successfully engineered thick tissues must include vasculature. As biological approaches alone such as VGEF have fallen short of their promises, one may look for an engineering approach to build microvasculature. With the advent of cell printing, one may be able to build precise human microvasculature with suitable bio-ink. Human Microvascular Endothelial Cells (HMVEC) and fibrin were studied as bio-ink for microvasculature construction. Endothelial cells are the only cells to compose the human capillaries and also the major cells of blood vessel intima layer. Fibrin has been already widely recognized as tissue engineering scaffold for vasculature and other cells, including skeleton/smooth muscle cells and chondrocytes. In our study, we comprehensively studied changes in heat shock protein expression and cell membrane morphogenesis in printed mammalian cells with thermal inkjet printers. The heat shock protein expression of the printed cells has minor difference between the untreated cells and lower than manually heated cells. The cell membrane of printed cells developed pores which allow small molecules such as propidium iodide and dextran molecules (up to 70kD) to pass. We then precisely fabricated micron-sized fibrin channels using a drop-on-demand polymerization. When printing HMVEC cells in conjunction with the fibrin, we found the cells aligned themselves inside the channels and proliferated to form confluent linings. The 3D tubular structure was also found in the printed patterns. We conclude that cell printing technology can be used for precise cell seeding in tissue engineering fabrication with minor effect and damages to the printed mammalian cells.