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.
