Biointegrating Dialysis Access Graft with Self Stabilizing Flow

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 DESCRIPTION (provided by applicant): Objective: The goals of this Phase II SBIR proposal are to evaluate longer-term patency and safety of a novel hemodialysis access graft design (ePTFE treated with textured microporous silicone exterior layer) and complete the necessary development steps to prepare the device for clinical evaluation. The Phase I feasibility study demonstrated markedly superior patency and reduction of neointimal hyperplasia compared to untreated ePTFE controls through 12 weeks in a sheep model. Significance: The need for frequent treatments (at least 3x per week) makes maintenance of reliable vascular access for hemodialysis patients extremely challenging. As a result of high maturation failure in autogenous arteriovenous (AV) fistulas (the preferred vascular access option) and a reluctance to use AV grafts (the safest alternative) due to longer-term patency concerns, more than half of all first-year hemodialysis patients, and more than 20% longer term, are treated via unsafe "last-resort" infection-prone catheters. Loss of patency by AV grafts is primarily due to development of neointimal hyperplasia at the venous anastomosis, which causes progressive narrowing of the lumen, leading to unstable low flow followed by thrombosis failure. Successful clinical introduction of an AV graft overcoming the hyperplasia problem would increase access options, and especially, enable a significant reduction in the use of high-risk catheters. Innovation: A number of factors, including surgical trauma at time of implant, graft-vein compliance mismatch, and unfavorable hemodynamic shear stress patterns are known to contribute to neointimal hyperplasia. But the underlying root cause of the problem that causes synthetic AV grafts to fail is the self-reinforcing "death spiral" feedback loop (hyperplasia causes low flow, which upregulates the advance of hyperplasia). By treating ePTFE grafts with an exterior biointerface that prevents the formation of a fibrous perigraft tissue capsule, the usual mechanical constriction effects are eliminated. The retained natural dynamic compliance of the perigraft tissue permits greater freedom for elastic and vibratory motion of the graft wall. This reduces compliance mismatch and provides more favorable stress conditions at the ePTFE-neointima interface. It also changes the usual flow effect of hyperplasia. An increase in stenotic resistance is compensated via a mechanism that widens the upstream hydraulic diameter. This appears to replace the pathologic feedback loop with a more favorable self-stabilizing feedback loop. The promising Phase I results suggest that this approach can lead to a major leap in AV graft clinical performance and reliability. Approach: Specific aims are 1) evaluating long-term patency, 2) demonstrating cannulation safety, and 3) completing requisite function and reliability testing. The proposed R&D steps will support a subsequent IDE application for a First-In-Human Early Feasibility Study for this Class II device. Project success would offer a safer and more reliable treatment option for a large fraction of the dialysis patient population.