Researchers at Duke University (Duke) have engineered a bandage that captures and holds a pro-healing molecule at the site of a bone break to accelerate and improve healing. In a proof-of-principle study with mice, the bandage helped to accelerate callus formation and vascularization to achieve better bone repair by 3 weeks. The research points toward a general method for improving bone repair that could be applied to biodegradable bandages, implant coatings, or bone grafts. The results were published earlier this year in Advanced Materials.
In 2014, Shyni Varghese, PhD, professor of biomedical engineering, mechanical engineering and materials science, and orthopedics at Duke, discovered that the biomolecule adenosine plays a large role in spurring bone growth. After further study, researchers in her laboratory found that the body naturally floods the area around a new bone injury with adenosine molecules, but those locally high levels are quickly metabolized and don’t last long. Varghese wondered if maintaining those high levels for longer would help the healing process.
However, “adenosine is ubiquitous throughout the body in low levels and performs many important functions that have nothing to do with bone healing,” Varghese said. Her solution to avoid unwanted side effects was to let the body dictate the levels of adenosine while helping the biochemical stick around the injury a bit longer. She and Yuze Zeng, a graduate student in her laboratory, designed a biomaterial bandage applied directly to the broken bone that contains boronate molecules, which grab onto the adenosine. The bonds between the molecules do not last forever, which allows a slow release of adenosine from the bandage without accumulating elsewhere in the body.
In the current study, Varghese and her colleagues first demonstrated that porous biomaterials incorporated with boronates could capture the local surge of adenosine following an injury. They then applied bandages primed to capture the host’s own adenosine or bandages preloaded with adenosine to tibia fractures in mice. After more than a week, the mice treated with both types of bandages were healing faster than those with bandages not primed to capture adenosine. After 3 weeks, while all mice in the study showed healing, those treated with either kind of adenosine-laced bandage showed better bone formation, higher bone volume, and better vascularization.
The results showed that not only do the adenosine-trapping bandages promote healing, they work whether they’re trapping native adenosine or are artificially loaded with it, which has important implications in treating bone fractures associated with aging and osteoporosis.
“Our previous work has shown that patients with osteoporosis don’t produce adenosine when their bones break,” Yuze said. “These early results indicate that these bandages could help deliver the needed adenosine to repair their injuries while avoiding potential side effects.”