Each year, tens of thousands of women receive mastectomies as a way to treat or prevent breast cancer. Many of them opt to receive reconstructive surgery to restore their original shape and form. Thanks to a new study by researchers at Carnegie Mellon University, reconstructive surgery may soon also restore mothers’ ability to nurse their children.
“In mammalian bodies, breast cells align to form hollow tubes, where milk is transported,” said Jimmy Hsia, a professor in the departments of Biomedical Engineering and Mechanical Engineering at Carnegie Mellon and corresponding author of the study. “To date, no one has been able to generate breast tissue with these hollow tubes. Our study is the first step toward realizing such functionalities in reconstructed breast tissues.”
The researchers aimed to understand which conditions induced breast cells to self-assemble into aligned, ductal shapes. Previous studies have shown that one key driver in cell alignment is substrate stiffness — that is, the stiffness of the tissue scaffold to which cells bind. However, those studies were performed mostly in two-dimensional environments in which cells bound to a flat surface, rather than a three-dimensional environment similar to real tissues.
“We grew breast cells in a 3-D environment, and they aligned themselves along certain geometrical features of the substrate,” Hsia said.
The researchers created 3-D scaffolds out of protein gel by placing the gel over meticulously shaped silicone molds. Depending on each mold’s shape, the gel solidified into different shapes with various levels of stiffness throughout. Then, breast cells were placed on top of the gel and the researchers recorded time-lapse microscopic video of the cells’ response to the scaffold environment.
The researchers found that the stiffness gradient — how stiffness changed throughout the tissue scaffold — was the key driver in how cells aligned themselves, rather than stiffness itself. Knowing this, researchers were able to organize breast cells into various structures, including continuous, long tubular shapes similar to those in breast tissues, with control of tube spacing.
“We know many people receive mastectomies and many of them do reconstruction, but none of these reconstructed breasts are functional,” Hsia said. “We believe we’re on our way toward achieving that.”