A Novel Electrospun Vascular Graft

新型静电纺血管移植物

• 批准号: 7805685
• 负责人: DAVID J VACHON
• 金额: $ 27.78万
• 依托单位: IASIS MOLECULAR SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805685
• 关键词: 3-Dimensional; Accounting; Adhesions; Adsorption; Affect; Age; Albumins; Alkanesulfonates; American; Angioplasty; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulation; Atherosclerosis; Autologous Transplantation; Behavior; Binding; Biocompatible; Biocompatible Materials; Biological; Biological Assay; Biological Markers; Blood; Blood Circulation; Blood Platelets; Blood Proteins; Blood Vessels; Blood flow; Blood specimen; Bypass; Caliber; Cardiovascular Diseases; Cardiovascular system; Caring; Cathepsins; Catheters; Cause of Death; Cell Adhesion; Cell Survival; Cerebrovascular Disorders; Cessation of life; Characteristics; Chemicals; Clinical Management; Coagulation Process; Connecticut; Construction Materials; Coronary Arteriosclerosis; Coronary Artery Bypass; Deposition; Devices; Disease; Drug Formulations; Elastases; Engineering; Environment; Equipment; Equipment Malfunction; Evaluation Studies; Event; Expenditure; Family; Fatigue; Fiber; Fibrin; Fibrinogen; Filament; Foreign Bodies; Frequencies; Generations; Goals; Harvest; Health; Health Care Costs; Healthcare Systems; Heart; Heart Diseases; Hospitalization; Human; Hydrogels; Implant; In Vitro; Infiltration; Inflammation; Inflammatory; Investigation; Ischemia; Label; Lead; Leukocyte Elastase; Limb structure; Measures; Mechanics; Mediating; Medicare; Medicine; Membrane; Metals; Methodology; Methods; Modification; Molecular; Monoclonal Antibodies; Morbidity - disease rate; Morphology; Mus; Myocardial Infarction; Operative Surgical Procedures; Outcome; P-Selectin; Pacemakers; Patients; Peptide Hydrolases; Performance; Peripheral; Peripheral arterial disease; Permeability; Pharmaceutical Preparations; Phase; Physiological; Platelet Glycoprotein GPIIb-IIIa Complex; Play; Polymers; Population; Porosity; Preparation; Procedures; Process; Production; Productivity; Property; Prosthesis; Proteins; Recombinants; Recovery; Research; Research Personnel; Residual state; Resistance; Resources; Role; Scanning Electron Microscopy; Site; Small Business Innovation Research Grant; Smooth Muscle Myocytes; Solutions; Solvents; Source; Spectroscopy, Fourier Transform Infrared; Stainless Steel; Stenosis; Stents; Sterile coverings; Stroke; Stroke prevention; Sum; Surface; Surgeon; System; Techniques; Testing; Textiles; Therapeutic Agents; Thick; Thrombolytic Therapy; Thrombosis; Thrombus; Time; Tissue Engineering; Tissues; Transplantation; Transplanted tissue; Tube; Tubular formation; United States; Universities; Urethane; Vascular Graft; Vascular Graft Occlusion; Vascular remodeling; Venous; Whole Blood; Woman; austin; base; biomaterial compatibility; cathepsin K; cerebrovascular; claudication; copolymer; cost; design; disability; drug development; economic impact; elastomeric; human capital; hydrophilicity; improved; inflammatory marker; inhibitor/antagonist; innovation; isobutylene; melting; men; neutrophil; novel; operation; polycarbonate; prototype; public health relevance; pulmonary artery endothelial cell; research study; response; success; total artificial heart; ventricular assist device; wound

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：一种具有独特的化学定制特性和加工特性的新型磺化聚合物，作为抗血栓性表面表现出了相当大的希望，已被证明是对中性粒细胞衍生蛋白酶的有效抑制剂。提出了第1阶段的SBIR测试来研究该聚合物作为血管移植物材料的混合物。提出的研究的主要特定目的是使用静电纺丝技术从这些材料中制造第一代血管移植物，并研究了随着血液下血液的表现。主要目的是最大程度地减少血小板粘附和激活。基于几项不同的研究揭示了该聚合物家族的有希望的生物应用属性，建立了对抗血管血管血液导管的这种创新和合理的方法。该第1阶段SBIR的最终目标是开发和识别固有的非血统和抗炎水凝胶（混合）表面，并具有潜在的应用为血管移植物和其他救生部心血管设备。 公共卫生相关性：心血管疾病（CVD）是美国男性和女性死亡和残疾的主要原因，目前影响超过7,000万美国人。总体而言，每年有超过600万次住院治疗心血管疾病。因此，CVD对我们国家医疗保健系统的经济影响不断增长，尤其是随着人口的年龄。当医疗保健成本支出和死亡和残疾的生产力下降时，2006年（美国）心脏病和中风的成本大于4000亿美元。 在心血管疾病的伞下，动脉粥样硬化诱导的周围动脉疾病（PAD），冠状动脉疾病（CAD）和脑血管疾病都是由于血管变窄的主要事件（狭窄）和/或咬合引起的，这引起了肿胀和/或闭塞，这引起了垂直肌肉和相关的肿胀型细胞（Smc），并引起了阳性的阳离子（Smc），并引起了肿胀的延伸（Smc）。血管重塑。狭窄和闭塞导致降低/流动血流的损失。对于PAD来说，这可能导致外围肢体的laurauration和组织发病率，而对于CAD，这可能会导致缺血，并且通常会导致致命的心肌梗塞，并且对于脑血管情况，这可能会导致中风。介入的血管内和/或手术治疗以去除血栓并重新建立血管流量，对于这些疾病的临床管理是必要的。血管内治疗涉及机械方法，例如导管介导的血管成形术，冷冻术和内部术以及药物治疗方法，例如经导管递送溶栓，抗血域和抗增殖药物。这些方法通常与支架结合在一起。近年来，有药物洗脱支架（DES）的发展，其中金属支架表面涂有载有药物的聚合物基质，以持续释放治疗剂。手术方法涉及旁路移植物，其中许多是由合成聚合物制成的（例如EPTFE）。对于其他心血管疾病，生物材料也起着重要作用。使用了包括起搏器，心室辅助设备和人造心脏的设备。上述所有设备都取决于与流血接触的合成材料。这些材料易于快速蛋白质（例如纤维蛋白原，纤维蛋白）沉积，变性和随后的血小板的粘附和激活可能导致凝块形成以及随后激活凝结和炎症事件。反过来，材料性能可能会受到损害，需要重复的血管内或外科手术。因此，这些患者通常需要永久性抗凝治疗，以防止中风和/或装置衰竭。因此，如上所述，设备上的蛋白质和血小板耐血液接触界面可以改善患者的预后并降低总体护理成本。 第一代合成血管移植是我们研究的主题。这些研究中的聚合物组成是磺化的块共聚物混合物，这些共聚物共聚物都表现出低血栓形成性，良好（湿）的机械性能，并且可以电纺化为3-D血管移植构建体。电物传（在流动下）的动态研究将用于了解血液中的材料行为。