3D printing aids cancer research

Hacking 3D printers to spit out squishy biological structures, Pitt and Carnegie Mellon University researchers are poised to help doctors make better breast cancer diagnoses.

Researchers at UPMC and CMU are collaborating under a new $800,000 grant to make 3D printers able to reproduce breast ducts — the conduit between mammary glands and nipples. In doing so, they hope to discover biomarkers — measurable characteristics associated with disease — to better diagnose which patients with precancerous breast duct lesions will develop an invasive, life-threatening form of breast cancer.

The researchers received the two-year grant from the U.S. Congressionally Directed Medical Research Program of the Department of Defense.

According to Priscilla McAuliffe, breast cancer surgeon, co-investigator on the DOD grant and Pitt assistant professor of surgery, only 20 to 50 percent of patients with non-invasive tumors localized to the breast duct — a condition known as ductal carcinoma in situ, or DCIS — will go on to develop invasive breast cancer.

Being able to identify which women need treatment and which do not would cut down on unnecessary radiation, surgery and pain, according to McAuliffe.

Common treatments for DCIS include lumpectomy plus radiation or mastectomy, and patients may also undergo hormone therapy, McAuliffe said. Recovering from surgery is painful and leaves scarring, while radiation can irritate skin and estrogen-blocking hormones carry a host of rare but serious side effects, such as blood clots, stroke and uterine cancer.

Adam Feinberg, co-principal investigator on the DOD grant and a materials science and biomedical engineering professor at CMU, published a 2015 article in the journal Science Advances showing that it is possible to replicate intricate soft tissue structures with a 3D printer.

“You can start to ask the question, given a certain kind of tumor: Is it more invasive in certain architectures?” Feinberg said. “You can change now each independently so you can start to understand what the mechanism is. Maybe the architecture itself, regardless of the kind of tumor, would promote invasion. Or maybe it’s not the architecture and it’s purely the cells.”

Patricia Halpin-Murphy, president and founder of the Pennsylvania Breast Cancer Coalition and a breast cancer survivor for more than 20 years, is enthusiastic about what the 3D printing technology could mean for women with DCIS.

“For the patient, you’re told you have ductal carcinoma [in situ] and it may not proceed to invasive, but it could,” Halpin-Murphy said. “You say, ‘Well, what are my chances? Is there a 10 percent chance? A 50 percent chance?’ Right now we have no idea.”

According to McAuliffe, the ability to perform risk assessment on each patient would be transformative.

“It’s pretty well-known that we are doing too much surgery on patients with DCIS,” McAuliffe said.

Not knowing whether a given patient falls into the unlucky minority, McAuliffe never counsels her DCIS patients against treatment, even though up to 80 percent of them might not need it.

“Based on the results of this study, the hope is that we will identify biomarkers that we could then use to better risk-stratify patients,” McAuliffe said.

Before using these biomarkers to make surgical decisions, it is necessary to perform randomized clinical trials, McAuliffe said, which is a long-term goal.

The first step is to uncover the biomarkers, which requires a realistic model system with complete control, Feinberg said.

According to Feinberg, the only ways to currently study breast tumors in the lab are to culture tumor cells in a petri dish or to grow tumor cells under the skin of a rodent. Neither method allows researchers to trace how breast duct structure impacts tumor spread.

One big hurdle to printing breast ducts, Feinberg said, is that this tissue often collapses under its own weight.

“The challenge with these materials is that they’re super soft,” Feinberg said. “They collapse under their own weight. They’re kind of like Jell-O. A block of Jell-O would sit there just fine, like a cube. But once you try to make an intricate 3D structure, it would just fall apart.”

To solve this problem, Feinberg’s group developed a way to print soft tissue within a dissolvable gel.

“I compare it to the fruit you would see inside of a Jell-O mold,” Feinberg said.  “The Jell-O holds everything in position.”

Feinberg’s setup includes a standard consumer-grade MakerBot, a 3D printer that translates computer plans into physical objects. Normally the MakerBot’s extruder builds objects by secreting layers of plastic, but Feinberg created a custom extruder specifically designed to layer proteins and other molecules normally found in biological tissue.

The plans for this custom extruder are open-source, available to anyone through the National Institutes of Health website.

“There’s almost an infinite number of cool things you could do with this technology, [more] than our lab is ever going to be able to do, so we’ve been kind of proactive in getting the technology out there,” Feinberg said.

If the initial experiment reveals possible biomarkers for invasive DCIS, the next step is to correlate these biomarkers with patient outcomes. For this, the researchers can leverage Magee-Womens Hospital’s extensive breast tissue bank, McAuliffe said. The tissue bank contains information about tumor genetics and ductal structure — potential biomarkers — as well as patient outcome.

Beyond discovering better ways to diagnose invasive DCIS, Feinberg is excited for bioprinting to become a standard means of building realistic model systems in the lab.

“At some point in the not-too-distant future this will just be a standard piece of lab equipment, these bioprinters,” Feinberg said. “Ultimately, I think we will be able to print organs and do tissue repair with these things. That’s obviously further down the line, but I think it’s on the horizon.”