By repeating the process, Khademhosseini can build up larger and larger structures that resemble, for example, blood vessels running through tissue. And by combining building blocks of different shapes that fit together like a lock and key, Khademhosseini can build even more complex structures. Spherical blocks made by the MIT and Harvard researchers slip into the corners of star-shaped blocks.
“This will be an effective way to put the cells where we want them to be,” says Hai-Quan Mao, a materials scientist at Johns Hopkins University. “You can probably generate a tissue with a higher complexity” using the new method than is possible with a scaffold that has to be seeded with cells, he says.
“This initial demonstration is inspiring,” agrees Suichi Takayama, a biomedical engineer at the University of Michigan. Researchers have had success with self-assembling materials for nonbiological applications such as computer chips. “People have thought of self-assembling biological materials, but he’s actually done it,” says Takayama of Khademhosseini. However, both caution that the work is in its early stages, and scaling the process up to larger, ever more complex structures will be a challenge.
Mao says that the self-assembling cell blocks could also be used to study how adjacent cells influence each other during development. Creating structural complexity isn’t the only hurdle that tissue engineers face. They also need a better understanding of the chemical and environmental signals that will help them grow tissues from stem cells in the lab: just what influences a stem cell’s decision to become a liver cell or a blood-vessel cell? Signals from other cells play an important role, and Khademhosseini’s structures, through which cell-communication molecules such as growth factors readily diffuse, could be used to study how the tissue environment influences stem cells.
Khademhosseini is currently working on making more-complex self-assembling structures that resemble the repeating units of the liver, the pancreas, and the heart muscle.