Slippery, Omniphobic Coating to Prevent Thrombosis and Biofilm Formation on Peripheral Vascular Grafts

PROJECT SUMMARY Critical limb ischemia (CLI) affects 2 million Americans with peripheral artery disease (PAD) each year and is a frequent cause of persistent ulcers and wounds, amputations, hospitalizations with frequent re-admissions, and death due to reduced blood flow to the affected limb. Untreated, CLI patients survive under 2 years. The main treatment for CLI is to increase blood flow to improve limb perfusion using extremity artery bypass. When the patient’s own vein is insufficient peripheral vascular grafts (PVG), frequently made from expanded polytetrafluoroethylene (ePTFE), are used as a synthetic graft is used for both segments. Unfortunately, PVG have failure rates ranging from 20% to 50% within the first year of surgery, which increases to >60% after 5 years. The primary reasons for PVG failure are neointimal hyperplasia, occlusion via thrombosis, and infection. No current or in-development technology successfully addresses these challenges. FreeFlow Medical Devices (FFMD) is aiming to optimize and commercialize tethered liquid perfluorocarbon (TLP) coatings on medical devices. Our TLP coating stops the adhesion of all biological components (bacteria, fungi, blood components) to the surface of medical devices by immobilizing a thin layer of highly inert and biocompatible perfluorinated liquid. Our preliminary data demonstrate that our TLP coating effectively resists occlusion and pathogen colonization on vascular devices under physiological flow conditions. In this Fast Track proposal, we will investigate the ability of TLP PVG to resist occlusion, thrombus formation, and biofilm formation, which all contribute to graft dysfunction We will also finalize the TLP additive packaging for GMP manufacturing in Phase II. This will be achieved using six Aims. Phase 1 Aim 1. Perform a 90-day in vitro TLP PVG characterization to understand the durability and characteristics of the coating after 90 days. Phase 1 Aim 2. Perform a 60-day protein biofouling study to test the ability of TLP surfaces to resist protein adsorption since biofilm development, thrombus progression, and neointimal hyperplasia all begin with protein adsorption. Phase 1 Aim 3. Perform 30-day in vitro thrombogenicity testing. Phase 2 Aim 4. Obtain GMP- manufactured TLP PVG. Phase 2 Aim 5. Perform an efficacy study to compare the in vivo effectiveness of TLP PVG with standard PVG (BD Impra®) at reducing thrombin formation, neointimal hypoplasia, and stenosis. Phase 2 Aim 6. Initiate the 510(k) application process to obtain FDA premarketing approval and perform a biocompatibility study. These advances will allow FFMD to maximize the effectiveness of the TLP coating and dramatically improve PVG patient care by reducing graft failure dure to neointimal hyperplasia, infection, and thrombosis.