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One in eight women in the United
States will develop breast cancer. Of those,
many will undergo surgery to remove the tumor and will require some kind of
breast reconstruction afterward, often involving implants. Cancer is an elusive
target, though, and malignant cells return for as many as one-fifth of women
originally diagnosed, according to the American Cancer Society.
Would it be possible to engineer implant materials that might drive down
that rate of relapse? Brown
University biomedical
scientists report some promising advances. The team has created an implant with
a “bed-of-nails” surface at the nanoscale that deters cancer cells from
dwelling and thriving. Made out of a common federally approved polymer, the
implant is the first of its kind, based on a review of the literature, with
modifications at the nanoscale that cause a reduction in the blood-vessel
architecture on which breast cancer tumors depend—while also attracting healthy
breast cells.
“We’ve created an (implant) surface with features that can at least
decrease (cancerous) cell functions without having to use chemotherapeutics,
radiation, or other processes to kill cancer cells,” said Thomas Webster,
associate professor of engineering and the corresponding author on the paper in
Nanotechnology. “It’s a surface that’s hospitable to healthy breast cells and less so for
cancerous breast cells.”
Webster and his laboratory have been modifying various implant surfaces to
promote the regeneration of bone, cartilage, skin, and other cells. In this
work, he and Lijuan Zhang, a fourth-year graduate student in chemistry, sought
to reshape an implant that could be used in breast reconstruction surgery that
would not only attract healthy cells but also repel any lingering breast cancer
cells. The duo created a cast on a glass plate using 23-nm-diameter polystyrene
beads and polylactic-co-glycolic acid (PLGA), a biodegradable polymer approved
by the FDA and used widely in clinical settings, such as stitches. The result:
An implant whose surface was covered with adjoining, 23-nm-high pimples. The
pair also created PLGA implant surfaces with 300-nm and 400-nm peaks for
comparison.
In laboratory tests after one day, the 23-nm-peak surfaces showed a 15%
decrease in the production of a protein (VEGF) upon which endothelial
breast-cancer cells depend, compared to an implant surface with no surface
modification. The 23-nm surface showed greater reduction in VEGF concentration
when compared to the 300-nm and 400-nm-modified implants as well.
It’s unclear why the 23-nm surface appears to work best at deterring
breast-cancer cells. Webster thinks it may have to do something with the stiffness
of malignant breast cells. When they come into contact with the bumpy surface,
they are unable to fully wrap themselves around the rounded contours, depriving
them of the ability to ingest the life-sustaining nutrients that permeate the
surface.
“This is like a bed-of-nails surface to them,” Webster said.
“I would guess that surface peaks less than 23 nm would be even better,”
Webster added, although polystyrene beads with such dimensions don’t yet exist. “The more you can push up that cancerous cell, the more you keep it from
interacting with the surface.”
The pair also found that the 23-nm semispherical surface yielded 15% more
healthy endothelial breast cells compared to normal surface after one day of
laboratory tests.
Webster and Zhang next plan to
investigate why the nanomodified surfaces deter malignant breast cells, to
create surface features that yield greater results, and to determine whether
other materials can be used.
