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An arteriovenous fistula is the current gold standard for chronic hemodialysis access. Tunneled catheters or synthetic grafts have poorer outcomes and much higher risks of infection. This report presents the first clinical use of a completely biological, allogeneic, nonliving, and human tissue-engineered vascular graft. Tissue-engineered vascular grafts built from allogeneic fibroblasts were implanted as shunts in three hemodialysis patients. The tissue-engineered vascular graft was stored for 9 months, without loss of mechanical strength. Implanted grafts showed no signs of degradation or dilation, with time points up to 11 months. Results of panel-reactive antibody and cross-reactivity tests showed no evidence of immune responses., (Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Since Scribner described the first prosthetic chronic dialysis shunt in 1961, the surgical techniques and strategies to maintain vascular access have improved dramatically. Today, hundreds of thousands of patients worldwide are treated with some combination of native vein fistula, synthetic vascular graft, or synthetic semipermanent catheter. Despite significantly lower efficacy compared with autologous fistulae, the basic materials used for synthetic shunts and catheters have evolved surprisingly slowly. The disparity between efficacy rates and concomitant maintenance costs has driven a strong campaign to decrease the use of synthetic grafts and catheters in favor of native fistulae. Whether arguing the benefits of Fistula First or "Catheter Last," the fact that clinicians are in need of an alternative to expanded polytetrafluoroethylene (ePTFE) is irrefutable. The poor performance of synthetic materials has a significant economic impact as well. End-stage renal disease (ESRD) accounts for approximately 6% of Medicare's overall budget, despite a prevalence of about 0.17%. Of that, 15%-25% is spent on access maintenance, making hemodialysis access a critical priority for Medicare. This clinical and economic situation has spawned an aggressive effort to improve clinical care strategies to reduce overall cost and complications. While the bulk of this effort has historically focused on developing new synthetic biomaterials, more recently, investigators have developed a variety of cell-based strategies to create tissue-engineered vascular grafts. In this article, we review the evolution of the field of cardiovascular tissue engineering. We also present an update on the Lifeline™ vascular graft, an autologous, biological, and tissue-engineered vascular graft, which was the first tissue-engineered graft to be used clinically in dialysis patients.

Previously we reported on the mid- to long-term follow-up in the first clinical trial to use a completely autologous tissue-engineered graft in the high pressure circulation. In these early studies, living grafts were built from autologous fibroblasts and endothelial cells obtained from small skin and vein biopsies. The graft was assembled using a technique called tissue-engineering by self-assembly (TESA), where robust conduits were grown without support from exogenous biomaterials or synthetic scaffolding. One limitation with this earlier work was the long lead times required to build the completely autologous vascular graft. Here we report the first implant of a frozen, devitalized, completely autologous Lifeline™ vascular graft. In a departure from previous studies, the entire fibroblast layer, which provides the mechanical backbone of the graft, was air-dried then stored at -80°C until shortly before implant. Five days prior to implant, the devitalized conduit was rehydrated, and its lumen was seeded with living autologous endothelial cells to provide an antithrombogenic lining. The graft was implanted as an arteriovenous shunt between the brachial artery and the axillary vein in a patient who was dependent upon a semipermanent dialysis catheter placed in the femoral vein. Eight weeks postoperatively, the graft functions without complication. This strategy of preemptive skin and vein biopsy and cold-preserving autologous tissue allows the immediate availability of an autologous arteriovenous fistula, and is an important step forward in our strategy to provide allogeneic tissue-engineered grafts available "off-the-shelf".

Background: Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft., Methods: Ten patients with end-stage renal disease who had been receiving haemodialysis through an access graft that had a high probability of failure, and had had at least one previous access failure, were enrolled from centres in Argentina and Poland between September, 2004, and April, 2007. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase (0-3 months) and effectiveness after haemodialysis was started., Findings: Three grafts failed within the safety phase, which is consistent with failure rates expected for this high-risk patient population. One patient was withdrawn from the study because of severe gastrointestinal bleeding shortly before implantation, and another died of unrelated causes during the safety period with a patent graft. The remaining five patients had grafts functioning for haemodialysis 6-20 months after implantation, and a total of 68 patient-months of patency. In these five patients, only one intervention (surgical correction) was needed to maintain secondary patency. Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation., Interpretation: Our proportion of primary patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative objectives (76% of patients 3 months after implantation) for arteriovenous fistulas, averaged across all patient populations.