Percutaneous osseointegrated prosthetic attachment or the direct skeletal attachment of artificial limbs, across the amputation stump skin into the residual bone, is a rapidly evolving technology that is now ready to be introduced into the United States, following greater than a decade of European trials that largely involved transfemoral amputees. Translational animal research carried out over the past seven years at the Bone and Joint Research Laboratory, VAH, Salt Lake City, Utah, has clarified principles of osseointegration, and bone and skin interface responses to chronic weight bearing of the residual bone containing a percutaneous implant. This information has produced new prosthetic designs that make the technique safer and more likely to succeed over the long-term. This translational animal data, gathered parallel to the European human data, has made possible an Early Feasibility Device Exemption (IDE) Pilot Program under the direction of the FDA. This trial is anticipated to begin in May 2014, at the VAH in Salt Lake City, Utah, and is funded by VA RR&D grant (RX001208-01). Ten transfemoral amputees, selected from the veteran and active military populations will receive the device. The critical limiting factor to the prior U.S. introduction of this technology has been an up to 30% infection rate at the implant/skin interface in European patients. Evolving designs and surgical techniques have lowered this incidence, but it remains remarkable that 70% to perhaps 95% of European patients now remain infection free with simply mild soap and shower hygiene at the stoma, and avoid the use of antibiotics. In fact antibiotics and disinfectants are often counter productive, and lead to antibiotic resistance. It seems increasingly evident that the key to this improbable success is the biology and mutualistic-commensal microbiota at the skin/implant interface: the bacterial guard dogs at the gate. This pending 10 patient Pilot Tria offers a unique, 1 year long, opportunity to study the evolving microbiota (Aim 1), and the wound healing and inflammatory cytokine environment of the skin/implant interface and surrounding skin as well as the systemic immune protein response to this percutaneous device (Aim 2); all determined at the same time points. Hopefully, this study will give measurable understanding as to why stomas do or don't become infected and to anticipate the onset of infection (Primary Goal). Serial skin swab bacterial DNA samples will be collected beginning with the Stage 1 surgery (device implantation with wound closure and primary wound healing) and 6 weeks later the Stage 2 surgery (establishment of the stoma; a chronic wound). Amplification of the bacterial 16S rRNA genes, obtained from this DNA, will be followed by sequencing on the Illumina MiSeq platform and will determine the resident microbiota at the stoma and adjacent thigh skin throughout the processes of primary wound healing and chronic stomal maturation. Simultaneous to the microbiome collection, venous blood and stomal exudate specimens will be obtained to compare systemic versus local inflammatory protein responses. The serial venous blood samples will be used to determine the instantaneous status of the host immune system and will be subjected to microarray analysis of immune system proteins using custom TaqMan microfluidic array cards (192 genes). This will measure the up and down regulation of host mRNA that translates the synthesis of immune system proteins i.e. cytokines and chemokines. Analysis of the stomal-exudate, using the BioPlex multiplex immunoassay and MagPix platform, will measure the levels of 27 wound healing and inflammatory cytokines in the local wound environment. Statistical analyses will compare each patient against himself/herself over time, and against the others (commonality of microbiota and infection vs. a stable, and uninfected stoma).