Why you should care
Because it’s not just time alone that heals all wounds.
It all started as a painless callus on Donna Morrow’s left foot. Since she knew her diabetes made her susceptible to foot ulcers, she saw her podiatrist, who shaved down the callus as a precaution. A few months later, her foot swelled so much she could barely walk. The callus had unfurled into gaping, infected ulcers whose appearance made her sick to her stomach. The former retiree from outside Philadelphia, now a director and founder of Victory Nutrition, spent months hooked to an antibiotic IV drip, hardly able to stand or shower, and underwent three skin grafts. “Is this ever going to end?” she wondered. Fears of amputation plagued her.
Morrow’s foot took more than a year to heal. She’s not alone: About half of all diabetics suffer from nerve damage, or neuropathy, which might mean a blister or a cut escapes notice until it progresses into something more serious. Diabetes also can lower blood circulation and immunity, which may slow healing. Now, researchers are devising solutions by upgrading run-of-the-mill balms, dressings and sutures with nanotechnology designed to speed and improve healing. The latest innovations include ointments that contain nanoparticles loaded with substances that trigger the migration of new skin cells to a targeted area, as well as scaffolds for these cells to populate. One “smart bandage” fluoresces to alert doctors of infection long before clinical symptoms appear.
With a tiny dart, it’s very easy to hit a large bull’s-eye.
Adam Friedman, George Washington University
It’s all part of the burgeoning field of nanomedicine, which deploys tiny particles and devices — tiny as in 100,000 times thinner than a sheet of paper — to deliver drugs and detect diseases. Although nanotech solutions to cancer and HIV tend to grab the headlines, the incidence of acute and chronic wounds promises only to grow as people live longer and become more susceptible to injury, whether from burns or surgery, or underlying medical problems like diabetes. Indeed, the research firm MarketsandMarkets projects the wound-care market will swell from $17 billion in 2016 to $20.4 billion by 2021. And amid the rising tide of antibiotic resistance, the more healing we can do sans antibiotics, the better.
Why the scaled-down approach? Shrinking an object exponentially increases its surface-area-to-volume ratio, which means “its ability to interact with its environment also goes way up,” explains Adam Friedman of George Washington School of Medicine and Health Sciences in Washington, D.C. At the nanoscale, antimicrobials have a better shot at reaching and killing pathogens, for instance, while compounds that stimulate production of wound-healing proteins are more likely to be engulfed by surrounding cells. “With a tiny dart,” Friedman says, “it’s very easy to hit a large bull’s-eye.”
Doctors already use nanocrystalline silver dressings, shrinking a metal used for centuries as an antimicrobial to render it even more potent. Now, Friedman and his colleagues are engineering nanoparticles to deliver compounds that nudge skin and other cells toward a wound — like curcumin, the yellow antioxidant in turmeric, also an age-old remedy. In experiments with mice, curcumin-laced nanoparticles increased blood vessel growth; accelerated and enhanced healing, resulting in more mature skin and collagen; and blocked MRSA (methicillin-resistant Staphylococcus aureus) in burn wounds.
Other nanoparticles shuttle molecules known as siRNA to silence genes that impair healing. When Dr. Amy S. Paller of the Northwestern University Feinberg School of Medicine in Chicago found that blocking the gene for the GM3 synthase enzyme led to normal wound healing, even in diabetic mice, she worked with colleague Chad Mirkin to design gold nanoparticles containing siRNA to target the gene. “Lo and behold, the mice that we treated were just so different,” Paller says. Their wounds took 12 days to heal, while those of untreated mice took 18 days — 50 percent longer. A separate study showing that knocking out the GM3 synthase gene reverses nerve loss and neuropathic pain in diabetic mice suggests that an ointment with her team’s nanoparticles could treat or even prevent diabetic wounds. Meanwhile, siRNA nanoparticles targeting the FL2 gene doubled the rate of healing in mice with cuts and burns; new skin cells even formed hair follicles and other complex structures. “They become real skin, not just a scar,” says David Sharp of the Albert Einstein College of Medicine in New York.
Beyond nanoparticles, researchers also are engineering dressings and bandages. Nanoscaffolds — dressings made from fibrous polymers — “serve as the ladders and streets for these cells to migrate along,” Friedman explains. National University of Singapore researchers, for instance, have found an aloe vera–coated scaffold embedded with human umbilical cord stem cells (to promote skin-cell renewal) accelerated and enhanced the healing of diabetic wounds in mice. Meanwhile, British researchers have engineered a bandage that glows green when bacterial toxins puncture nanoparticles in the dressing that contain a fluorescent dye. Toby Jenkins of the University of Bath says the bandage could allow doctors to act early and minimize the risk of resistance by indicating when a burn actually needs antibiotics.
To be sure, these therapies probably won’t enter the market for a few years. Researchers still need to conduct clinical trials and scale up the manufacturing process. “Safety — not just real safety, but the perception of safety — is the biggest hurdle,” Friedman says. Our bodies seem to metabolize nanoparticles quickly and excrete them as waste, although it’s less clear for metal nanoparticles. And we still don’t know how releasing them into, say, the water supply would impact the environment.
Some patients simply are eager to see them in the clinic. Although Morrow credits dietary supplement Prodovite for speeding up her healing process, “other things” — like nanotechnology — “are as exciting.” Tom Schoenemann, 60, of Calgary, Alberta, who has diabetic neuropathy, voices similar enthusiasm. “That’s awesome to hear,” the retired Canadian baker says. “If they’re giving free samples, I’ll take them.”