Khademhosseini’s group found that within an individual embryoid body, cells on the squishier, gelatin side took a different path from cells on the polyethylene glycol side. The gelatin is easier for the cells to push into, and this affects how they grow, directing them to become blood vessels. “They completely remodel the side that’s gelatin, digging through the gel, elongating, and forming blood-vessel-like sprouts,” says Khademhosseini. These cells also express chemical markers typical of blood-vessel precursor cells, called endothelial cells. The cells on the other side differentiated in a more chaotic manner. The researchers also watched what happened when they varied the molds to create gel blocks that contained more or less gelatin.
Khademhosseini hopes to further test the effects of different hydrogels. He also plans to embed different development-stimulating chemicals within the gels. Using chemical signals to influence stem-cell differentiation is a common approach, but controlling which parts of a group of cells are exposed to which chemical signals has been difficult. Other groups have used microfluidics devices to feed different chemicals to cells. Khademhosseini believes using the hydrogel will be easier.
“This is a creative new way to guide stem cell behavior using patterned hydrogels,” says Sarah Heilshorn, assistant professor of materials science and engineering at Stanford University. She says the most innovative aspect of the work is the ability to quickly make large numbers of the cell constructs. “This approach could be applied to a broad range of other biomaterials and cell types.”
Khademhosseini’s ultimate goal is to build cardiac tissue from the bottom up. “We’d like to seed cells to pattern branching vasculature through cardiac tissue,” he says. The multimaterial gel structures, he says, “can be the modules of our self-assembling cellular structures,” he says.