New Biological Solutions for Hemodialysis Access

Abstract

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.

Tissue engineering vascular grafts a fortiori: looking back and going forward

“…Clinical trials have been undertaken to evaluate the use of the cell-sheet--based strategy to create an arteriovenous (AV) shunt for haemodialysis access in patients with end-stage renal disease. Results demonstrate acceptable mechanical properties, good patency and low failure-to-mature rate for AV fistulas [23,54,55]. Although the results are promising, cell sheets have a long fabrication time, which can be attributed to the time-consuming maturation process in the bioreactor.…”

Arteriovenous access failure: more than just intimal hyperplasia?

“…The TEBV was evaluated as AVG in ten patients resulting in a primary patency rate of 78% and 60% after 1 and 6 months, respectively [77]. With spectacular progress in the field of vascular tissue engineering [78][79][80], the use of a TEBV might become a realistic alternative in the near future.…”

A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐Concept Animal Study in an Ovine Model

“…[2] On the other hand, biological or biosynthetic grafts, generated through tissue engineering approaches, either in vivo or in vitro, are characterized by time-consuming and costly manufacturing procedures, also implying the use of non-autologous cells, which might easily impair their regulatory approval and their present or future clinical widespread use. [3] In situ tissue engineering strategies, using acellular, totally or partially degradable, scaffolds that are gradually replaced/remodeled by the host, might represent a viable alternative, joining the main advantage of synthetic grafts (i.e., early puncturability) and the ones of biological substitutes (higher compatibility, remodeling capability, higher patency rates). [4][5][6] In this context, we have previously developed an electrospun hybrid vascular graft based on the combination of natural silk fibroin and synthetic poly-carbonate urethane (a blend named Silkothane), [7] which proved to be a potential candidate for an in situ engineering approach to arteriovenous shunting, due to its favorable mechanical properties, suitable permeability, nonhemolytic character, long clotting time, capability of sustaining adhesion of human umbilical vein endothelial cells in vitro, and early cannulation potential.…”