Prevention of Implant-Skin/Bone Interface Infection in Osseointegrated Prostheses with Photodynamic Therapy
Abstract
Injuries to the arms and legs sustained in battle commonly involve broken bones with open wounds (open fracture). Improvements in body armor and rescue strategies have increased the number of survivors of combat-related injuries. An unintended consequence of improved survival is an increase the number of wounded Warriors with lower extremity amputation, often at high level (like through the upper thigh) and/or in both legs. Combat-related trauma in Iraq and Afghanistan alone has resulted in over 1,600 major limb amputation through 2015, and more than one fifth of these Service Members have lost more than one limb. The negative functional consequences of this are profound. Traditional socket-based prostheses are associated with functionally limiting problems such as pain, skin ulcers, infections and swelling with inconsistent prosthesis fit, among others. Osseointegrated prostheses, in which a metal implant is anchored directly to residual bone, are functionally superior. Anchoring a prosthetic device to bone is a much closer to the physiology and mechanics of a non-amputated limb resulting in superior outcomes in terms of physical function, skin-related complications, and chronic pain and has the added benefit of vibratory sensation. However, an important barrier to widespread adoption of OI prostheses is infection at the implant-skin/bone interface. This proposal is the next step towards developing an at-home treatment method to prevent infection associated with OI prostheses using a light-sensitive FDA-approved medication that is applied topically (or directly on to the skin and metal) followed by targeted light application (called photodynamic therapy or PDT). Our group has clearly shown that PDT can even penetrate and eradicate bacteria protected within communities called biofilm, which is frequently present on metallic implants that are exposed to the environment. This is an animal study in a rabbit contaminated osseointegrated prosthesis model designed to evaluate the efficacy of PDT at reducing the bioburden (amount of bacteria present) and preventing infection and to optimize the dose of PDT to optimize reduction in bacteria and minimize injury to adjacent skin. At the completion of this study, we will be prepared to translate PDT into human patients with demonstrated efficacy and an optimal dose of the topical medication and targeted light. This study will have a substantial military benefit and clinical impact on the care and outcome of patients with leg or foot amputations. Complications, chronic pain and functional limitations are common using currently available socket-based prostheses. Critical to regaining normal lifestyles and returning to active duty is having a highly functional prosthetic device which can be achieved more frequently and reliably using bone-anchored or osseointegrated prostheses. This study will fill a critical gap in our knowledge base and will serve as preparation for an early phase clinical trial in human patients with osseointegrated prostheses. We believe that this work will pave the way for widespread adoption of functionally superior OI prostheses and transform the lives of patients with amputation that are a result of both battlefield injuries and/or civilian causes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310800
Entities
People
- Ida Gitajn
Organizations
- Dartmouth–Hitchcock Medical Center
- United States Army