‘Bed-of-nails’ breast implant deters cancer cells

Researchers at Brown University have created an implant that appears to deter breast cancer cell regrowth. Made from a common federally approved polymer, the implant is the first to be modified at the nanoscale in a way that causes a reduction in the blood-vessel architecture that breast cancer tumors depend upon, while also attracting healthy breast cells. Results are published in Nanotechnology.

PROVIDENCE, R.I. [Brown University] — 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.

A selectively inhospitable surface
A bumpy “bed of nails” surface does not allow cancerous
cells to gather the nutrients they need to thrive — possibly
because cancerous cells are stiffer and less flexible than
normal cells, which can manage the bumps and thrive.
Credit: Webster Lab/Brown University

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 (dimensions one-billionth of a meter, or 1/50,000th the width of a human hair) 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 lab 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-nanometer-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-nanometer-high pimples. The pair also created PLGA implant surfaces with 300-nanometer and 400-nanometer peaks for comparison.

In lab tests after one day, the 23-nanometer-peak surfaces showed a 15-percent 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-nanometer surface showed greater reduction in VEGF concentration when compared to the 300-nanometer and 400-nanometer-modified implants as well.

It’s unclear why the 23-nanoneter 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 nanometers 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-nanometer semispherical surface yielded 15 percent more healthy endothelial breast cells compared to normal surface after one day of lab 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.

The National Institutes of Health’s National Center for Research Resources and the Hermann Foundation funded the research. Michael Platek at the University of Rhode Island helped with the electron spectroscopy for chemical analysis.

- by Richard Lewis

Nanomaterials Studies Advance Cancer Research

Graduate student Lijuan Zhang and associate professor Thomas Webster have conducted research with nanomaterials that may lead to a potential breakthrough in cancer research. Their recent research, "Decreased lung carcinoma cell functions on select polymer nanometer surface features" was published in Journal of Biomedical Materials Research A.  

Behind the purple doors of a sixth-floor Barus and Holley Lab, Thomas Webster, associate professor of engineering, works small but thinks big. His work with nanomaterials, tiny devices implanted into the human body, has led to a potential breakthrough in cancer research.

Webster, director of the University's NanomedicineLaboratory, has been studying and developing nanotech implants for the past 11 years. His team had created rough implants covered in tiny "nano-features"— microscopic bumps ­— to "mimic the natural roughness of healthy skin," he said. "Current orthopedic implants are flat and smooth, but healthy skin and bone have bumps."

Two years ago, graduate student Lijuan Zhang approached Webster with a radical idea — exploring how nano-features would interact with cancer cells.

"Being the adventurous person I am, I said, ‘Let's try it,'" Webster said. It was completely new territory for Webster, but he said he was excited to see what would happen.

Within a year of research, a blink of an eye in lab time, Zhang approached Webster with results they both found fascinating. The addition of 23nm nano-features to a petri dish with both cancerous and healthy cells caused a significantly lower density of cancer cells over time.

Webster said he was pleased and intrigued by the results, but he knew the tests needed to be run at least three more times to verify any findings.

Zhang ran another trial and again found a lower density of cancer cells, but she also found something new — the nano-features inhibited the synthesis of a protein that aids in tumor growth.

The tests had initially been conducted with lung cancer cells, but later tests used breast cancer and bone cancer cells. Both reacted in the same manner — the nano-features lowered the density of cancer cells and decreased the synthesis of the tumor growth protein.

The next step is finding real-world applications, Webster said. "In order for any of this research to be useful, we need a company. We need to transition from the lab bench to a real product."

Webster said he hopes to apply their discovery to animal models and eventually human trials. "If all goes well, a product could appear in five years," he said.

By Hannah Kerman/BDH

Nanotechnology and nanomaterials: Promises for improved tissue regeneration is top article in NanoToday

A paper written by Dr. Lijie Zhang ScM'07 PhD'09, now an assistant professor at George Washington University, and Brown University associate professor Dr. Thomas Webster, is currently the most downloaded article from the journal NanoToday.

The article is entitled "Nanotechnology and nanomaterials: Promises for improved tissue regeneration" NanoToday 4(1):66-80, 2009 and covers recent advancements in the use of nanotechnology to improve tissue growth for numerous implant applications.

Summary
Tissue engineering and regenerative medicine aim to develop biological substitutes that restore, maintain, or improve damaged tissue and organ functionality. While tissue engineering and regenerative medicine have hinted at much promise in the last several decades, significant research is still required to provide exciting alternative materials to finally solve the numerous problems associated with traditional implants. Nanotechnology, or the use of nanomaterials (defined as those materials with constituent dimensions less than 100 nm), may have the answers since only these materials can mimic surface properties (including topography, energy, etc.) of natural tissues. For these reasons, over the last decade, nanomaterials have been highlighted as promising candidates for improving traditional tissue engineering materials. Importantly, these efforts have highlighted that nanomaterials exhibit superior cytocompatible, mechanical, electrical, optical, catalytic and magnetic properties compared to conventional (or micron structured) materials. These unique properties of nanomaterials have helped to improve various tissue growth over what is achievable today. In this review paper, the promise of nanomaterials for bone, cartilage, vascular, neural and bladder tissue engineering applications will be reviewed. Moreover, as an important future area of research, the potential risk and toxicity of nanomaterial synthesis and use related to human health are emphasized.

Link to NanoToday:
http://journals.elsevier.com/17480132/nano-today/

Link to full article:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B82X8-4TVY5PJ-2&_user=489286&_coverDate=02/28/2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000022678&_version=1&_urlVersion=0&_userid=489286&md5=0590ae25

Engin grad earns outstanding dissertation award

Lijie Zhang (Ph.D., BME, 2009), won the Joukowsky Family Outstanding Dissertation Award for her thesis "Biologically Inspired Rosette Nanotube Nanocomposites for Bone Tissue Engineering, Orthopedic, and Vascular Applications".

The letter reads that she was selected out of over 200 PhD graduates this year for her superior achievement in research. The award will be given out during the Graduate School Commencement ceremony.

Lijie is now completing a post-doc at Rice University.