Knowledge of the medicinal benefits of silver is thought to date back to 300 BC, when the influential Greek physician Hippocrates wrote about treating wounds with the chemical element. In the early 20th century, drops containing silver were used to treat eye ailments, and soldiers fighting in World War I were known to use silver leaf to treat their infected wounds. What makes silver special in medicine is its ability to eradicate bacteria and other pathogens. While silver’s antimicrobial properties have been well documented, concerns about toxicity have limited its use in orthopedics. Armed with an updated CE Mark and a silver-based product that’s been streamlined for surgeries, the California-headquartered company Silver Bullet Therapeutics aims to change that.
OrthoFuzIon™, the company’s flagship product, is a silver-coated bone screw system that’s been carefully engineered to release just enough silver ions to kill local bacteria, but not enough to be toxic to patients. To achieve this, the silver coating is delicately blended with platinum within the same plain to develop a galvanic circuit. Over 800 OrthoFuzIon screw sizes have been approved to suit myriad orthopedic devices.
The company recently announced that their technology earned an updated CE Mark and plans to enter the German market in 2021 with its new screw. The CE Mark contains no anatomical, clinical or design limitations, according to Silver Bullet’s Founder, President and CEO Paul Chirico.
“The biggest thing around our CE change is that we’re no longer limited to an indication of foot and ankle. This technology can be used anywhere in the body,” said John Barr, M.D., a Professor of Radiology and Neurosurgery at UT Southwestern and one of the medical experts credited with developing the technology behind OrthoFuzIon. “Obviously infections are not limited to the foot and ankle, so that’s really a big change.”
Dr. Barr went on to say that the new iteration of the product has been streamlined for surgeries and doesn’t require orthopedic surgeons to do anything out of the ordinary to install the screws.
While the updated CE Mark only applies to screws, Silver Bullet Therapeutics plans to apply their proprietary silver coating to other orthopedic devices. However, the company believes there is already a profound benefit in making their proprietary coating available for screws.
“Screws are on the outside and the inside of the bone, so a lot of infection is intramedullary,” said Amir Matityahu, M.D., an orthopedic trauma surgeon at the University of California San Francisco who consulted with Silver Bullet Therapeutics to develop OrthoFuzIon. “The head of the screw is outside the bone on the plate, and then the rest of the screw is inside the bone. If you just put the coating on your plate and not in the screws, you’re not going to reach the internal portion of the bone where infection can also occur. That’s the advantage of starting with a screw.”
According to Chirico, OrthoFuzIon has been in development since 2011. “We were initially constrained by traditional methods of plating, and we certainly did not want to go down the road of nanotechnology because of the known toxicology associated with that,” Chirico said. “It took us a few years to zero in on sputtering, pretreatment and post-treatment processes of the device to get maximal antimicrobial activity with a minimalist approach to how much we added.”
The updates to OrthoFuzIon will be launched during a time when medical communities around the world are becoming increasingly alarmed about drug-resistant bacteria or superbugs. According to a 2019 report published by the CDC, more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35,000 people die as a result. “The estimated national cost to treat infections caused by six multidrug-resistant germs identified in the report and frequently found in health care can be substantial—more than $4.6 billion annually.” In 2020, the World Health Organization called antibiotic resistance “one of the biggest threats to global health, food security and development today.”
When asked about how well OrthoFuzIon could stand up to superbugs, Chirico pointed to a 2016 study conducted using a 4mm x 10mm screw to test its product against the top six CDC superbugs. According to Chirico, the coated screw had killed all of the bacteria within 24 hours, whereas the dangerous superbugs flourished on the uncoated screws that were also tested during the study at Emery Pharma.
“We were most impressed by the ‘adherence’ results for the OrthoFuzIon device against the top six antibiotic-resistant pathogens that are commonly implicated in hospital-acquired infections,” said Ron Najafi, Ph.D., President and CEO of Emery Pharma in a press release. “The results of OrthoFuzIon preventing these pathogens from adhering to them were simply impressive.”
OrthoFuzIon is designed to kill local bacteria within a 24-hour period after surgery and prevent infection indefinitely after. “It's all about introducing a high level initially and then staying above the Surface Inhibitory Concentration (SIC) for a period of time, about 60 days, then tailoring off to an amount that is negligible,” explained Chirico.
Orthopedic device companies, contract manufacturers, coating companies and academia continue to pursue the use of silver orthopedic devices. The balance lies in making the release of silver ions safe for the patient.
Dr. Barr said that Silver Bullet and Houdin Dehnad, Ph.D., the expert credited with helping engineer OrhoFuzIon have made the process “simple.”
“Houdin is an absolute genius of being able to figure out how to tailor the different materials to release the amount of silver we want at the rate we want for the duration we want, and also to manage where they resist abrasion so they don't flake off,” he said.
Silver Bullet received its initial CE Mark in 2015. The company plans to work with FDA to eventually bring their product to the U.S. market.
Patrick McGuire is a BONEZONE Contributor.