Nitric oxide releasing nanomatrix wrap to enhance dialysis fistula maturation

DESCRIPTION provided by applicant More than U S patients have end stage renal disease and over utilize hemodialysis as their renal replacement modality of choice The Achilles Heel in the care of dialysis patients is the development of a functioning and durable vascular access preferably an arteriovenous fistula The annual cost of treating vascular access dysfunction totals over one billion US dollars This is largely due to the high proportion of arteriovenous fistulas AVFs that fail to mature After creation sixty percent of AVFs fail to mature successfully for dialysis use due to early venous neointimal development and inadequate vasodilation At present there are no effective therapies to promote vascular access maturation Endomimetics has developed a nanomatrix coating that mimics the characteristic properties of native endothelium This nanomatrix can be coated on biocompatible electrospun polycaprolactone ePCL sheets that are then wrapped around the dialysis AVF at the time of creation The coating provides sustained release of nitric oxide NO over months thus recruiting and retaining endothelial cells and endothelial progenitor cells It also incorporates a endothelial cell adhesive ligand that promotes endothelial cell retention and migration The sustained release of NO also promotes appropriate vasodilation necessary for healthy AVF maturation This coating also limits smooth muscle SMC proliferation an additional benefit since SMC proliferation plays a significant role in AVF non maturation The nanomatrix coating is a biocompatible peptide based material and is coated on ePCL sheets by simple water evaporation This coating method minimizes the risk of inflammatory responses In this Phase I SBIR we propose to evaluate and optimize the coating for ePCL sheets This will include evaluation of physical characteristics and assessing effects on endothelial and smooth muscle cell growth In collaboration with Dr Lee at the University of Alabama at Birmingham the efficacy of this coating will be evaluated in an established rodent AVF model and compared with non coated ePCL sheets Development of a coating that promotes AVF maturation may have significant impact in the treatment of patients requiring dialysis With successful completion of Phase I we plan to move forward in Phase II to large animal studies PUBLIC HEALTH RELEVANCE Arterovenousfistula non maturation occurs in of patients of hemodialysis patients receiving an arteriovenous fistula AVF This results in significant morbidity and mortality because of long term dialysis catheter use Endomimetics LLC has developed a novel nanomatrix coating which when applied to an electrospun sheet and wrapped around the AVF at time of creation could promote and enhance healthy AVF maturation and reduce the risk of longer term complications