Published October 19, 2017
A newly patented technology developed as a collaboration in the departments of Biomedical Engineering, Orthopaedics, and Microbiology and Immunology is at the heart of an Office of Naval Research (ONR) grant focused on preventing and treating orthopaedic implant-related infections.
The research involves using Cathodic Voltage Controlled Electrical Stimulation (CVCES) for bacterial biofilm infection control in osseointegrated prosthetic limbs.
Mark Ehrensberger, PhD, assistant professor of biomedical engineering, is principal investigator on the two-year, $1.1 million grant.
Co-investigators are Anthony A. Campagnari, PhD, professor of microbiology and immunology; Albert H. Titus, PhD, professor and chair of biomedical engineering; and Thomas R. Duquin, MD, clinical assistant professor of orthopaedics.
Osseointegrated prosthetic limbs are a relatively new alternative to traditional socket prostheses that can be connected directly to the skeleton, providing a more secure fixation.
“With osseointegrated prosthetic limbs, you have a titanium rod implanted into the bone of the residual limb,” Ehrensberger says. “And this internal rod protrudes through the soft tissues and skin to attach and secure the external artificial limb.”
The idea comes from the dental community because the approach is very similar to what is used in dental implants, he notes.
“Osseointegrated prosthetic limbs can offer several advantages over socket prosthetic limbs,” says Ehrensberger, who is also director of the Kenneth A. Krackow, MD, Orthopaedic Research Laboratory in the Department of Orthopaedics.
“For example, in traumatic and combat-related amputation, heterotopic ossification, or abnormal bone formation, can often occur in the soft tissue of the residual limb. Wearing a socket prosthesis causes compression in the residual limb, which can be quite painful when there are little spicules of bone in the soft tissue,” he says.
“The osseointegrated prosthesis is an attractive alternative in this situation because it does not transfer compressive load through the soft tissue, but rather, directly to the skeleton.”
In its efforts to provide injured service members the best possibility to recover function and a normal lifestyle, the Department of Defense has implemented an osseointegration program.
“It is a broad initiative combining clinical care and translational research across several academic institutions, industry partners and military medical centers,” says Ehrensberger, who is a member of the program’s steering committee.
“Where we fit in is on infection control. One of the challenges with osseointegrated prostheses is that the percutaneous site can become prone to infection, with some reported infection rates as high as 18 to 30 percent,” he says.
If a problematic bone infection is established in the residual limb, amputations may have to occur at a higher level.
“That really becomes an issue because for an amputee, every inch of bone is precious, and preserving residual limb length is essential to maintaining function for the patient,” he says.
What Ehrensberger and his interdisciplinary team have proposed is using the percutaneous titanium rod as an electrode since it is readily accessible in a noninvasive manner.
The research project’s title is “An Electrochemical Sense and Respond Osseointegrated Prosthesis.”
“In one mode, we are utilizing knowledge of the electrochemical properties of the implant material and directly sensing microenvironmental changes to assess tissue integration status or to detect if there is an infection developing,” he says.
“In another mode, the implant becomes an active electrode through which we can deliver electrical stimulation either prophylactically to prevent an infection from establishing or therapeutically to eradicate an existing infection” Ehrensberger adds.
The CVCES technology utilizes a potentiostatic three-electrode configuration to precisely modulate the voltage-dependent electrochemical processes at the surface of the metallic implant to elicit the antimicrobial response, while maintaining biocompatibility with the bone tissue.
The interdisciplinary team has performed antimicrobial studies that are showing synergy between applying electrical stimulation and the use of traditional antibiotics.
The researchers took a particular strain of MRSA (methicillin-resistant Staphylococcus aureus) that is typically treated with the antibiotic vancomycin and experimented with in vitro infection models.
“Our data is showing if you treat with just the drug, you get some reduction in bacteria,” Ehrensberger says. “If you treat with only the stimulation, you also get some reduction. But if you apply stimulation and drug together, you can get complete clearance of the bacteria.”
The intention of the first phase of the ONR grant is to identify the most promising stimulation parameters from in vitro studies and then to move into animal model testing in the second phase. In phase one, the researchers have also been developing an implantable wireless stimulation device that will be utilized in the animal studies.
“I am very encouraged by our work to date. We are really starting to optimize our stimulation parameters to work in conjunction with what’s clinically done right now,” Ehrensberger says. “The goal is to utilize this new stimulation technology to enhance the current protocols for infection prevention and eradication.”
“One of the things we envision is making a docking station that can connect to the osseointegrated prosthesis at night,” he says. “Utilizing this platform, diagnostic tests could be performed, such as electrochemical sensing of an infection, and if we need to deliver a prophylactic or therapeutic electrical stimulation, it could be done perhaps while the patient is sleeping.”
The study has been years in the making and benefited from two internal UB grants.
Ehrensberger first received an “idea development” grant from the Congressionally Directed Medical Research Program (CDMRP) in 2010.
“Oftentimes you need to have a lot of preliminary data to obtain significant funding,” he notes. “This initial CDMRP grant was really based on the merits of the idea and the potential impact it could have. The funding enabled us to do some preliminary work and file for a patent for our novel CVCES technology.”
The two internal UB grants were essential for keeping the project moving forward, Ehrensberger says. In 2013, the work was supported by a Bruce Holm Memorial Catalyst Fund grant from UB Technology Transfer, and in 2015 the researchers received a grant through UB’s CTSA Pilot Studies program.
“With this critical internal funding, we were able to build upon our initial proof-of-principle data and begin optimizing the electrical stimulation parameters,” he says. “Through these UB-supported projects, we were able to generate significant and compelling data that was instrumental to the success of obtaining the larger ONR grant and also attracting interest from our commercialization partner, Garwood Medical Devices.”
Garwood Medical Devices LLC, a participant in the START-UP NY economic development program, has an exclusive licensing agreement with UB to commercialize the CVCES technology for biomedical infection control applications.
The ONR grant is funded through its new Monitoring Osseointegrated Prostheses Initiative.
Consisting of academic researchers and industrial firms from around the world — U.S., Australia, Hong Kong and New Zealand, to name a few — the initiative is a diverse group all focused on enhancing osseointegrated prostheses.
“It is designated as an ONR SwampWorks program, which is high-risk, high-reward, early-stage research that has potential to quickly deliver high-impact solutions for the military,” Ehrensberger says. “Which in this case is to enhance the quality of life for injured service members that have suffered limb amputation.”