University of Vermont
Rachael Oldinski would like to cure cancer, replace cartilage, and patch punctured lungs—with seaweed. Okay, it’s more complicated than that. But one spring afternoon in the University of Vermont’s Engineered Biomaterials Research Laboratory, the professor points to three of her graduate students and four undergrads. “Everyone here works with alginate,” she says, “which is purified seaweed.”
You might call it the goo lab. One student holds up a clear strip of gelatinous plastic that he made with several natural products including alginate and collagen. “The collagen is from the livestock industry,” he says. “It’s exactly the same stuff as goes into Jell-O.”
Another worked with Oldinski to create a jelly to see how well it will mimic the properties of the inner region of the human spine. Normally, this nucleus pulposus gel is the shock absorber within the discs between each vertebra. “But in disease, that jelly leaks out,” Oldinski says. So, the lab team is looking for a “material replacement,” she says.
“We also work, literally, with snot,” Oldinski says with an unguarded smile. “We have several projects that use hyaluronic acid,” the clear goo that the body creates to lubricate joints, shape eyeballs and, yes, “it’s snot,” Oldinski says.
Underlying the great-fun-with-squishy-stuff ethos of the lab, Oldinski is making discoveries that are deadly serious. She and her team—with support from the National Institutes of Health— have been exploring how to use alginate gels to create a kind of Band-Aid for the lung.
Whether from a car crash or disease or battlefield injury, once a lung is punctured it is difficult to seal and heal, since it is constantly inflating and deflating. Oldinski, her former graduate student Spencer Fenn, and others in both UVM’s College of Engineering and Mathematical Sciences and Larner College of Medicine have developed a patch that looks promising for clinical use. Once it is freeze-dried, a surgeon will be able to cut a piece of this hydrogel, apply it to the wound and let it rehydrate from the body’s own water. Then, using a scope with a green light, transform the goopy patch into an adhesive lung sealant. This innovation promises to be non-toxic and a recent study by the lab team shows that the patch can withstand lung-like pressures.
But Oldinksi is engineering these seaweed patches to do more. “What if you had damage to the lung as result of a tumor? Would you not want to seal that hole and return its mechanical function--but also treat any cancer cells that are left?” In other words, she’s learning how to use seaweed to patch damaged tissue and serve as a sophisticated tool for localized drug delivery, particularly for cancer treatments.
Fenn holds up a slide to the light. It glows a faint pink. It’s red because of doxorubicin hydrochloride— a chemotherapy drug. He’s mixed the drug into the alginate patch, as well as into alginate microparticles—that were also mixed into the liquid before being treated with the green light. “It’s a hydrogel inside a hydrogel,” he says.
“You could apply this patch on the site of the surgery,” Fenn says, “which would release high concentrations of the chemo drug there, but keep systemic concentrations down.”
Another of Oldinski’s former graduate students, Tianxin Miao, has worked with her to create nanoscale alginate particles. “They’re like a meatball of water, seaweed, calcium chloride and a drug,” Miao says. Except the balls are thousands of times smaller than the period on the end of this sentence. What Miao, Oldinski, and Jeffrey Spees, a professor in UVM’s Larner College of Medicine, have discovered they can do with these tiny particles of seaweed may “be huge,” Oldinski says. “It could be a brand-new treatment for cancer.”
The nanospheres Miao created are “really ninja beads,” Oldinski says. Recent reports show that a naturally occurring protein, called fibroblast growth factor 2, that sends signals on the outside of cells, behaves very differently—if it gets inside a cell. There, it can function like a hormone to inhibit growth and kill cells—including cancers. Using this knowledge, Miao and Oldinski mixed the growth factor into a highly engineered form of their alginate meatballs, called alginate-graft-PEG, and then released them into a sample of human lung cancer cells.
The scientists were pleased and amazed that the nanospheres slipped past the cells’ surface receptors for the growth factor—and got inside. There, the tiny alginate balls moved to the cells’ nuclei “and released their bomb: the growth factor,” Oldinski says. “It kills the cancer.”
At its foundation, Oldinski’s aim is to imitate nature “to replace nature,” she says—but then to use the replacement materials to restore regular biological function. In another line of research, she and her students are working on seaweed-based products that could be used to temporarily replace damaged cartilage but would also carry drugs and stem cells that themselves would attract the body’s own stem cell production. “If we can lead the body to produce its own new cartilage,” say Tianxin Miao, “then you don’t need a plastic patch anymore.”