Advancing Antimicrobial Photodynamic Therapy to Prevent Infection in Osseointegrated Prosthesis Patients

PROJECT SUMMARY Over 2.2 million US patients are estimated to have limb loss, with the number projected to rise to 3.6 million by 2050. The current standard for rehabilitation and mobility following amputation is a socket-mounted prosthesis which bears force through the skin of the residual limb. However, this traditional attachment method is frequently associated with functionally-

limiting problems including chronic pain, discomfort, and medical complications at the residuum- prosthesis interface. Osseointegration (OI) for reconstruction in amputees is a procedure in which a metal implant is directly anchored to the residual bone. A prosthetic limb is then attached to the distal end of the implant (abutment) which protrudes through a small opening in

the skin. Directly anchoring a prosthetic device to the bone much more closely matches the physiology and mechanics of a non-amputated limb, resulting in superior outcomes with regards to physical function, skin-related complications, chronic pain and osseoperception. However, to date, risk of infection represents the biggest barrier to widespread adoption of

OI prostheses due to the transcutaneous nature of the implant. Antimicrobial photodynamic therapy (aPDT) is a treatment modality in which a topical photosensitizing (PS) agent (FDA- approved 5-aminolevulinic acid, 5-ALA) is applied, is preferentially taken up by microbial cells, and is subsequently activated by application of light, producing cytotoxic singlet oxygen and free

radicals that eradicate microorganisms. Our previous work has demonstrated that topical aPDT eliminates >95% of both biofilm-based and planktonic bacteria both in vitro and in an in vivo rodent model—substantially more effective as a microbiocide than any other currently utilized adjuvant treatment strategy. Thus, our overall objectives in this proposal are to build an

optimized light administration device and evaluate feasibility, acceptability, usability, preliminary efficacy and safety in human patients with OI prostheses. This represents the next step toward attainment of our long-term goal, which is to facilitate widespread implementation of OI by integrating aPDT into the regular wound-care regimen thus prevening infection. To attain our

objectives two aims will be pursued: (1) design and build a light tunnel optimized for delivery of aPDT at the implant-skin interface and (2) evaluate feasibility, acceptability, usability, preliminary efficacy and safety for infection prevention in OI patients. The completion of this study is a critical step to the development and implementation of a multicenter definitive RCT

powered to detect a reduction in rate of infection in OI patients. Successful reduction in infection would be paradigm-shifting.