A novel sulfonated polymer with unique chemically tailorable properties and processing characteristics has shown considerable promise as a thrombo- resistant surface and has been proven to be an effective inhibitor against neutrophil-derived proteases. Phase 1 SBIR testing is proposed to investigate blends of this polymer as vascular graft material. The major specific aims of the proposed research involve the fabrication of a first generation vascular graft from these materials using an electrospinning technique and investigating the performance of the graft with blood under flow. The primary objective is to minimize platelet adhesion and activation. This innovative and rational approach to a thrombo-resistant blood conduit is founded on the basis of several different studies that have revealed promising bioapplicable attributes of this polymer family. The end-goal of this Phase 1 SBIR is to develop and identify an inherently non-thrombogenic and anti-inflammatory hydrogel (blend) surface with potential application as a vascular graft and other lifesaving cardiovascular devices. , ,
Public Health Relevance: Cardiovascular disease (CVD) is the leading cause of death and disability for both men and women in the U.S., presently affecting more than 70 million Americans. Overall, more than 6 million hospitalizations occur each year for treatment of cardiovascular diseases. Consequently, the economic impact of CVD on our nation's health care system continues to grow, especially as the population ages. The cost of heart disease and stroke in 2006 (U.S.) was greater than $400 billion, when healthcare cost expenditures and lost productivity from death and disability are accounted for. Under the umbrella of cardiovascular diseases, atherosclerosis-induced peripheral artery disease (PAD), coronary artery disease (CAD) and cerebrovascular disease all result from the primary event of vessel narrowing (stenosis) and/or occlusion due to dysregulated formation of clots and associated inflammatory events involving smooth muscle cell (SMC) infiltration, neointimal proliferation and maladaptive vascular remodeling. Stenosis and occlusion lead to reduction/loss of antegrade blood flow. For PAD, this may lead to claudication and tissue morbidity of peripheral extremities, while for CAD this can lead to ischemia and often fatal myocardial infarction and, for cerebrovascular situations, this may lead to stroke. Interventional endovascular and/or surgical treatment to remove thrombus and to reestablish vascular flow is necessary for clinical management of these diseases. Endovascular treatments involve mechanical approaches like catheter-mediated angioplasty, cryoplasty and enderactomy and, pharmacotherapeutic approaches like transcatheter delivery of thrombolytic, anti-platelet and anti-proliferative drugs. Often these approaches are combined with stenting. Recent years have seen the development of drug eluting stents (DES) where the metal stent surface is coated with a drug-loaded polymer matrix for sustained release of therapeutic agents. Surgical approaches involve bypass grafts, many of which are made of synthetic polymers (e.g. ePTFE). For other cardiovascular diseases biomaterials also play an important role. Devices including pacemakers, ventricular assist devices, and the total artificial heart are used. All of the aforementioned devices depend upon synthetic materials that come into contact with flowing blood. These materials are prone to rapid protein (e.g. fibrinogen, fibrin) deposition, denaturation and subsequent adhesion and activation of blood platelets potentially leading to clot formation and the subsequent activation of coagulation and inflammatory events. In turn, material performance can be compromised necessitating recurring endovascular or surgical procedures. As such, these patients generally require perpetual anticoagulation therapy in order to prevent stroke and/or device failure. Thus, protein- and platelet-resistant blood-contacting interfaces on devices as mentioned above can improve patient outcomes and reduce the overall cost of care. A first-generation synthetic vascular graft is the subject of our investigation. The polymer compositions in these studies are sulfonated block copolymer blends that have demonstrated low thrombogenicity, good (wet) mechanical properties, and can be electrospun into 3-D vascular graft constructs. Dynamic studies of the electrospun graft (under flow) will be used to understand the materials behavior in blood.
Thesaurus Terms: 3-D;3-Dimensional;Accounting;Adhesions;Adsorption;Affect;Age;Albumins;Alkanesulfonates;Alkyl Sulfonates;Alkylsulfonate Compound;American;Angioplasty;Anti-Inflammatories;Anti-Inflammatory Agents;Anti-Inflammatory;Anticoagulation;Antiinflammatories;Antiinflammatory Agents;Aortocoronary Bypass;Apoplexy;Assay;Atheroscleroses;Atherosclerosis;Atherosclerotic Cardiovascular Disease;Autograft;Autologous Transplantation;Autotransplant;Behavior;Binding;Binding (Molecular Function);Bioassay;Biocompatible;Biocompatible Materials;Biologic Assays;Biological;Biological Assay;Biomaterials;Bizzozero's Corpuscle/Cell;Blood;Blood Circulation;Blood Coagulation Factor I;Blood Coagulation Factor One;Blood Factor One;Blood Neutrophil;Blood Platelets;Blood Polymorphonuclear Neutrophil;Blood Proteins;Blood Sample;Blood Segmented Neutrophil;Blood Vessels;Blood Flow;Blood Specimen;Bloodstream;Body Tissues;Brain Vascular Disorders;Bypass;Cd62p Antigens;Caliber;Cardiac Diseases;Cardiac Disorders;Cardiac Infarction;Cardiovascular;Cardiovascular Body System;Cardiovascular Diseases;Cardiovascular System;Cardiovascular System (All Sites);Caring;Cathepsins;Catheters;Cause Of Death;Cell Adhesion;Cell Survival;Cell Viability;Cellular Adhesion;Cerebral Stroke;Cerebrovascular Apoplexy;Cerebrovascular Disease;Cerebrovascular Disorders;Cerebrovascular Stroke;Cerebrovascular Accident;Cessation Of Life;Characteristics;Chemicals;Circulation;Clinical Management;Clotting;Coagulation;Coagulation Factor I;Coagulation Factor One;Coagulation Process;Connecticut;Constriction, Pathologic;Constriction, Pathological;Construction Materials;Coronary Arteriosclerosis;Coronary Artery Bypass;Coronary Artery Bypass Grafting;Coronary Artery Bypass Surgery;Coronary Artery Disease;Coronary Artery Disorder;Coronary Atherosclerosis;Death;Deetjeen's Body;Deposit;Deposition;Devices;Diameter;Disease;Disorder;Dressing;Drug Formulations;Drugs;Elastases;Engineering;Engineerings;Environment;Equipment;Equipment Malfunction;Esteroproteases;Ethyl Carbamate;Ethyl Urethan;Evaluation Studies;Event;Expenditure;Extremities;Ftir;Ftir Spectroscopy;Factor I;Factor One;Failures, Device;Family;Fatigue;Fiber;Fibrin;Fibrinogen;Fibrinolytic Therapy;Filament;Foreign Bodies;Formulation;Formulations, Drug;Fourier Transform Infrared Spectroscopy;Frequencies (Time Pattern);Frequency;Gmp-140;Gp Iib Iiia Complex;Gpiib-Iiia Receptors;Generations;Glycoproteins Iib-Iiia;Goals;Graft Material;Graft Occlusion, Vascular;Granulocyte Elastase;Hosp;Harvest;Hayem's Elementary Corpuscle;Health;Health Care Costs;Health Costs;Health Insurance For Aged And Disabled, Title 18;Health Insurance For Aged, Title 18;Health Insurance For Disabled Title 18;Healthcare Costs;Healthcare Systems;Heart;Heart Diseases;Heterophil Granulocyte;Hospitalization;Human;Human, General;Hydrogels;Inflm;Implant;In Vitro;Infiltration;Inflammation;Inflammatory;Integrin Alpha-Iib Beta-3;Integrin Alphaiibbeta3;Intracranial Vascular Disorders;Investigation;Investigators;Ischemia;Lecam-3;Label;Lack Of Energy;Lead;Leiomyocyte;Leukocyte Elastase;Limb Structure;Limbs;Lysosomal Elastase;Malfunction, Equipment;Mammals, Mice;Man (Taxonomy);Man, Modern;Marrow Neutrophil;Marrow Platelet;Measures;Mechanics;Mediating;Medicare;Medication;Medicine;Membrane;Metals;Method Loinc Axis 6;Methodology;Methods;Methods And Techniques;Methods, Other;Mice;Microscopy, Electron, Scanning;Moab, Clinical Treatment;Modification;Molecular;Molecular Interaction;Monoclonal Antibodies;Morbidity;Morbidity - 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