This project directly addresses the FY19 PRORP ARA Focus Area of “skin-Implant Interface.” There have been a total of 2,216 deployment-related, major lower- and upper-limb amputations sustained by 1,705 U.S. Service members during 2001-2017, including 453 Service members with multiple major limb amputations. Mainstream socket prosthetic limbs have limitations including discomfort, skin breakdown, and infections, which result in an impaired quality of life for the amputee. A new type of prosthetic limb involving a titanium implant directly anchored to the bone (osseointegrated) offers promising advantages and improvement over the currently used socket prosthetic limbs. These advantages include direct load transfer to the skeleton, better control of prosthetic movement, and potentially the return of some sensory function known as osseoperception. However, the widespread utilization of this prosthesis has been limited due to concerns of infection originating at the site where the titanium implant protrudes through the skin.

Using previous funding from the CDMRP and Office of Naval Research, our research team has developed a new technology that applies electrical stimulation directly to orthopaedic implants to kill bacteria and prevent infections. We have shown in the laboratory and in small animals that, in the absence of using antibiotics, this electrical stimulation can kill a broad range of bacteria that are known to cause problematic orthopaedic implant infections. This electrical stimulation even works to kill bacteria that are resistant to antibiotic treatment. We have patented this electrical stimulation technology and are working with Garwood Medical Devices (GMDTM) to commercialize this technology for clinical use in humans. GMDTM has developed a first-generation device known as the Biofilm Disruption Device (BDDTM) and has already received early guidance from the U.S. Food and Drug Administration regarding regulatory pathway and anticipates filing for De Novo classification/approval in 2022.

The main goal of this project is to assess how effective the electrical stimulation technology (BDDTM) is at preventing and eradicating infections of percutaneous titanium implants in a large animal (Yucatan Miniature Swine) model. This large animal model was specifically developed to realistically represent the percutaneous site of osseointegrated prosthetic limbs. Previous work has shown this to be an ideal animal model to use for studying soft-tissue wound healing and infection associated with the skin-implant interface of osseointegrated prosthetic limbs. Specifically, in this project, there will be three main research aims. Aim 1 will evaluate the use of electrical stimulation to enhance soft-tissue healing and integration of percutaneous titanium implants. This will be quantified with methods to track the cellular and molecular processes related to soft-tissue wound healing and also by visual microscopic examination of samples of the integrated tissue and percutaneous implants. Aim 2 and 3 will evaluate the use of electrical stimulation to prevent (Aim 2) and eradicate (Aim 3) infections of percutaneous titanium implants at the skin-implant interface. In these tests, we will use a bacteria (methicillin-resistant Staphylococcus aureus [MRSA]) that is known to develop very problematic and difficult to treat orthopaedic implant infections. We will quantify the amount of bacteria present in the soft tissues and implant surfaces at intervals before and after exposure to the bacteria and electrical stimulation therapy. We will also use visual microscopic examination of the integrated tissues and percutaneous implants to assess for the presence of infection. Our general hypothesis, based upon our previous data and experience, is that the electrical stimulation will effectively prevent and eradicate infections and promote enhanced soft-tissue healing and integration at skin-implant interface.

We believe that, when infection risk is minimized and soft-tissue healing is promoted, osseointegrated prosthetic limbs can lead to functional independence for patients who cannot otherwise tolerate a prosthesis. Infection control and enhanced tissue-integration with CVCES would allow amputees to realize the full potential of osseointegrated prostheses and improve the quality of life for wounded Service members. Furthermore, IAIs are problematic in all areas of orthopaedics (joint replacement, spine, trauma) and dentistry (peri-implantitis). In the long term, we believe that optimized CVCES delivered by the BDDTM can provide solutions to all of these clinical areas because CVCES (1) is broadly applicable to all passivated implant metals used in orthopedics; (2) has potent, broad-spectrum, stand-alone antimicrobial properties; and (3) synergistically enhances existing antibiotics. Our commercialization partner, GMDTM, has a proven track record of commercialization experience, a robust business model, and a strategic product development/regulatory plan that will incorporate feedback from the proposed work to ensure a successful venture.