SBIR-STTR Award

The objective of this Phase I SBIR proposal is to evaluate a novel vascular graft design for use as the arteriovenous (AV) graft component of a new needle-free access port. Significance: Hemodialysis patients require painful punctures with large needles for vascular access on a near-daily basis. This worsens quality of life, and the repeated tissue trauma makes maintenance of a reliable long-term access difficult. AV grafts (the safest option for the 40% of patients unable to sustain an autogenous fistula) are prone to thrombosis at the venous anastomosis and other needle-trauma-related complications such as infection and hematoma. A device that could circumvent the issues associated with needlesticks and provide patient- friendly long-term vascular access with low complication rate would have major impact. Innovation: STARport is a new percutaneous hemodialysis port under development that provides blunt cannula access to the inside of an AV graft. It uses Healionics' proprietary STAR(R) biomaterial at the tissue interface to overcome the exit site infection issue that stymied earlier attempts to commercialize similar port devices. STAR's sphere-templated structure has precisely-dimensioned microporosity optimized to promote capillary ingrowth, minimize fibrotic encapsulation, and facilitate the body's natural defenses against biofilm. A successful STARport must also overcome the anastomotic thrombosis issue, made especially challenging because the tissue-anchored port transmits hyperplasia-inducing stresses to the venous anastomosis. We propose to test 'STARgraft' (a vascular graft made from STAR biomaterial) as the AV component for STARport. STAR's optimized pore structure, which takes advantage of a narrow pore size 'sweet spot' where pore openings are the minimum size permitting vascular ingrowth, is ideally suited for promoting a thromboresistant bloodflow surface. Its exceptional biocompatibility should also create a smoother transition at the graft- vein anastomosis than existing graft materials, potentially reducing neointimal hyperplasia. STARgraft also features the STAR biointerface on the exterior of the graft to resist infection. Approach: The Phase I target milestones - to be achieved in a sheep model - are: 1) histological evidence that STARgraft (with midgraft connection to STARport) reduces neointimal hyperplasia compared to control ePTFE grafts, and 2) demonstration that STARgraft extends the functional patency of the device. A Phase II would address detailed device testing and preclinical demonstration of device longevity and function for dialysis as prerequisites for a clinical Early Feasibility Study.

Thesaurus Terms:
Address;Affect;Anastomosis - Action;Arteriovenous Fistula;Base;Biocompatible Materials;Biomaterial Compatibility;Biomechanics;Blood;Blood Capillaries;Blood Circulation;Blood Coagulation Factor;Blood Flow;Blood Vessel Prosthesis;Blood Vessels;Cannulas;Capillary;Clinical;Combat;Complication;Cytokine;Data;Design;Development;Device Or Instrument Development;Devices;Dialysis Procedure;Dimensions;Effectiveness;End Stage Renal Failure;Equipment;Exhibits;Feasibility Studies;Fiber;Fistula;Geometry;Goals;Healed;Healing;Hematoma;Hemodialysis;Housing;Hyperplasia;Immunocompromised Host;Implantable Device;Improved;Infection;Innovation;Investments;Lead;Left;Longevity;Maintenance;Marketing;Mechanics;Medical;Methods;Microbial Biofilms;Modeling;Needles;Needlestick Injuries;Novel;Pain;Patients;Penetration;Performance;Phase;Polytetrafluoroethylene;Population;Preclinical Testing;Property;Prosthesis;Public Health Relevance;Puncture Procedure;Quality Of Life;Repaired;Research;Resistance;Resistance To Infection;Risk;Serum;Sheep;Site;Skin;Small Business Innovation Research Grant;Spottings;Stress;Structure;Success;Surface;Technology;Testing;Thrombosis;Tissue Trauma;Tissues;Transplanted Tissue;Trauma;Vascular Graft;Veins;Venous;

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.

Public Health Relevance Statement:


Public Health Relevance:
A significant portion of end stage renal disease (ESRD) patients on hemodialysis rely on vascular access via an implanted prosthetic arteriovenous graft. These devices suffer from progressive flow blockages and require periodic interventions to restore patency. We have discovered that these blockages can be greatly reduced by adding an outer layer of our structured porous biomaterial onto conventional grafts. This layer minimizes graft contraction and loss of flow caused by the squeezing effect of tissue fibrous capsule formation around the implants. This project is to verify the initial observations, demonstrate the improved graft function over an extended time period and qualify the design towards human use.

NIH Spending Category:
Assistive Technology; Bioengineering; Cardiovascular; Kidney Disease

Project Terms:
Anastomosis - action; Arteriovenous fistula; base; Biocompatible Materials; Blood Circulation; Blood Vessels; Caliber; Cannulations; capsule (pharmacologic); Cardiac; Catheters; Cessation of life; Clinical; constriction; Coupled; design; Development; Devices; Dialysis patients; Dialysis procedure; End stage renal failure; Equilibrium; Failure (biologic function); Feasibility Studies; Feedback; Foreign Bodies; Freedom; Frequencies (time pattern); Goals; graft function; Hemodialysis; hemodynamics; high risk; Human; Hyperplasia; Implant; improved; Infection; innovation; Intervention; Lead; Lesion; Life; Maintenance; Mechanics; Medical; Methods; Modeling; Motion; Needles; novel; Operative Surgical Procedures; Outcome; Particulate; Pathologic; patient population; Patients; Pattern; Performance; Phase; Physiologic pulse; Plant Roots; pressure; prevent; Prosthesis; public health relevance; Pulmonary Embolism; Qualifying; Recommendation; Recurrence; Research; research and development; research clinical testing; Resistance; Resort; Risk; Safety; shear stress; Sheep; Silicones; Small Business Innovation Research Grant; Stenosis; Stress; Structure; success; Surface; Testing; Thrombosis; Time; Tissues; Trauma; Ultrasonography; Vascular Graft; Veins; Venous