(582c) Bionanomatrix Gel for Arteriovenous Fistula Maturation for Hemodialysis

Chronic kidney disease (CKD) affects over 850 million people worldwide and is projected to become the fifth leading cause of years of life lost by 2040. Each year, more than 2 million patients progress to end-stage renal disease (ESRD), requiring dialysis or kidney transplantation. Arteriovenous fistulas (AVFs) are the preferred form of vascular access for hemodialysis due to their superior long-term patency and lower infection risk. However, 30–60% of AVFs fail to mature adequately, primarily due to maladaptive vascular remodeling, including insufficient outward remodeling and neointimal hyperplasia.

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), plays a critical role in maintaining vascular homeostasis by promoting vasodilation, inhibiting smooth muscle cell proliferation, and reducing oxidative stress. To harness these benefits, we developed a perivascular NO-releasing bionanomatrix gel designed to promote endothelialization and provide sustained, localized NO delivery. In a rat AVF model, application of this gel at the anastomosis site resulted in a 60% reduction in neointimal hyperplasia and significant improvements in hemodynamic parameters.

Building on these promising results, we are advancing to a translational porcine AVF model, which closely replicates human vascular anatomy and hemodynamics, to further evaluate clinical potential. In this model, the NO-releasing bionanomatrix gel mitigated neointimal hyperplasia and reduced collagen I deposition, helping to prevent vessel stiffening and enabling outward remodeling. Improved hemodynamics—characterized by increased luminal dilation and blood flow—suggest that NO enhances adaptive responses to shear stress and counteracts maladaptive wall thickening.

These findings underscore the therapeutic potential of localized NO delivery to address AVF maturation failure, a significant barrier in hemodialysis management. Success in this large-animal model could pave the way for first-in-human trials, offering a novel strategy to improve AVF outcomes, reduce morbidity in ESRD, and address a critical unmet need in CKD care.