SBIR-STTR Award

Objective: The objective of this Phase I SBIR project is to validate a new synthetic vascular graft construction designed to reduce infection failures of arteriovenous (AV) grafts. Building upon a previously demonstrated approach for preventing venous-end stenosis (via suppression of perigraft fibrotic encapsulation), the new design includes features that enhance the effectiveness of the body’s natural immune defenses against device-associated infections. A successful outcome will verify this design’s capability to address both of the major causes of AV graft failure (stenosis and infection). Significance: Establishing and maintaining vascular access for hemodialysis patients is extremely challenging. As a result of slow maturation times and maturation failures in autogenous arteriovenous fistulas (the preferred vascular access option) and a reluctance to use synthetic AV grafts (the next safest alternative) due to infection concerns and poor patency, more than half of all first-year patients, and more than 20% longer term, are treated via “last-resort” infection- prone catheters. There is a desperate need for an improved AV graft to reduce reliance on catheters. Innovation: Healionics’ STARgraft AV+ is a new way to address the AV graft infection problem. Featuring a microporous sheath with tightly controlled pore geometry (30-µm spherical pores interconnected by 12-µm openings), placed over the exterior of a conventional ePTFE graft, the new device is designed to combat infection via multiple mechanisms: 1) Immune cell-accessible surface area within the pore space is maximized, concentrating favorably-activated protective macrophages. 2) The pore structure and surrounding tissue become permanently vascularized and fibrotic encapsulation is suppressed, enabling phagocytic immune cells to migrate freely. 3) Remarkably, the high concentration of immune cells and unimpeded cell migration within the protective sheath layer has been shown to provide a “Halo Effect”, infusing the pore spaces of the inner ePTFE core layer with protective immune cells. This effect appears to further reduce infection vulnerability by accelerating fibrotic tissue repair within the holes of the graft wall after needle punctures. Approach: Performance of the new AV graft will be evaluated in an established sheep model, adapted to allow bacterial challenges via repeated mock dialysis sessions (i.e., cannulation with large needles). The specific aim is to demonstrate superior infection control (i.e., a reduced level of bacterial colonization) compared to conventional grafts. Impact: A new AV graft that reliably avoids stenosis and infection problems would provide a much-improved vascular access option and improved quality of life for a large segment of the dialysis patient population, especially by reducing hospitalizations and mortality due to catheter-related bloodstream infections. Full development would also have an enormous collateral economic benefit – even a 10% reduction in access-related severe infections would save more than $1B annually to the health care system.

Public Health Relevance Statement:
NARRATIVE Of the nearly 500,000 end-stage renal disease (ESRD) patients on hemodialysis in the US, nearly 100,000 rely on vascular access via an implanted synthetic arteriovenous graft (AVG). These devices have infection rates as high as 20% per patient year. We have discovered that our structured porous biomaterial applied as an outer layer on conventional grafts may enhance the natural immune response to infections caused by the repeated cannulations needed for dialysis. This project will validate the infection- resistant modified AV graft in a preclinical animal study. v0.2

Project Terms:
Achievement; Address; Animals; Antibiotics; antimicrobial; antimicrobial drug; Area; Arteriovenous fistula; Bacteria; Biocompatible Materials; Blood capillaries; Blood Vessels; Cannulations; capsule; Catheter-related bloodstream infection; Catheters; cell motility; Cells; Clinical; Clinical Trials; combat; Construction Materials; cost; Data; design; design and construction; Development; Devices; Dialysis patients; Dialysis procedure; Dose; Economics; Effectiveness; End stage renal failure; Ensure; Failure; Feasibility Studies; first-in-human; Geometry; graft failure; Halo Effects; Healthcare Systems; Hemodialysis; Hospitalization; Human; Immune; Immune response; Implant; implantable device; improved; Infection; Infection Control; infection risk; innovation; Intervention; Life; macrophage; Microbial Biofilms; Modeling; mortality; Needles; Outcome; patient population; Patients; Performance; Phagocytes; Phase; Physiologic arteriovenous anastomosis; Pilot Projects; pre-clinical; Pre-Clinical Model; prevent; protective effect; Puncture procedure; Quality of life; repaired; Resistance; Resistance to infection; Resort; Sheep; Silicones; Site; Skin; Small Business Innovation Research Grant; Stenosis; Structure; Surface; Time; tissue repair; Tissues; Vascu