In recent years, tissue engineers have made great progress in 3-D printing very small sections of a wide variety of functional tissue types. Printing tissue masses that include the intricate blood vessel networks needed to support larger volumes remains a challenge, however. Progress on this front has been slow, as illustrated by the fact that this reported research is a step forward in terms of size and complexity:
Researchers have invented a method for 3D bioprinting thick vascularized tissue constructs composed of human stem cells, extracellular matrix, and circulatory channels lined with endothelial blood vessel cells. The resulting network of vasculature contained within these deep tissues enables fluids, nutrients and cell growth factors to be controllably perfused uniformly throughout the tissue. To date, scaling up human tissues built of a variety of cell types has been limited by a lack of robust methods for embedding life-sustaining vascular networks. Building on earlier work, researchers have now increased the tissue thickness threshold by nearly tenfold, setting the stage for future advances in tissue engineering and repair.
In the study, the team showed that their 3D bioprinted tissues could sustain and function as living tissue architectures for upwards of six weeks. They demonstrated the 3D printing of one centimeter-thick tissue containing human bone marrow stem cells surrounded by connective tissue. By pumping bone growth factors through the supporting vasculature lined with the same endothelial cells found in our blood vessels, the team induced cell development toward bone cells over the course of one month. The novel 3D bioprinting method uses a customizable, printed silicone mold to house and plumb the printed tissue structure. Inside this mold, a grid of vascular channels is printed first, over which ink containing living stem cells is then printed. The inks are self-supporting and strong enough to hold shape as the structure's size increases with each layer of deposition. At intersections meeting within the foundational vascular grid, vertical vascular pillars are printed, which interconnect a pervasive network of microvessels throughout all dimensions of the stem cell-laden tissue. After printing, a liquid composed of fibroblasts and extracellular matrix fills in the open regions around the 3D printed tissue, cross linking the entire structure. The resulting soft tissue structure is replete with blood vessels, and via a single inlet and outlet on opposite ends of the chip, can be immediately perfused with nutrients to ensure survival of the cells.