Resorbable Small Diameter Vascular Grafts

可吸收小直径血管移植物

• 批准号: 7925991
• 负责人: Eun Seok Gil
• 金额: $ 20万
• 依托单位: SPECTRASILK, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925991
• 关键词: Address; Animal Model; Arteries; Award; Biochemical; Biocompatible Materials; Biopolymers; Blood; Blood Proteins; Blood Vessels; Businesses; Bypass; Caliber; Cardiovascular Diseases; Cause of Death; Cell Communication; Cell Proliferation; Cells; Chemistry; Clinical; Clinical Trials; Coronary; Coronary Artery Bypass; Coupling; Data; Dependence; Development; Drug Formulations; Endothelium; Engineering; FDA approved; Fibroins; Goals; Harvest; Health; Heparin; Human; In Situ; In Vitro; Mechanics; Mediating; Medical Device; Methods; Modeling; Molecular Weight; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Outcome; Paclitaxel; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Platelet Activation; Polyethylene Glycols; Principal Investigator; Process; Production; Property; Proteins; Rattus; Recovery; Recruitment Activity; Regulation; Request for Applications; Research; Research Design; Silk; Site; Smooth Muscle Myocytes; Spatial Distribution; Surface; Technology; Time; Tissue Engineering; Tissues; Tube; United States; Vascular Diseases; Vascular Graft; base; catalyst; chemical group; clinical practice; design; femoral artery; functional outcomes; graft function; improved; in vivo; inhibitor/antagonist; innovation; interest; migration; programs; public health relevance; repaired; response

DESCRIPTION (provided by applicant): This application entitled "Development, Characterization, and Application of Multifunctional Antithrombogenic Silk Grafts," is a response to the Request for Applications (RFA) number RFA-OD- 09-009: Recovery Act Limited Competition: Small Business Catalyst Awards for Accelerating Innovative Research (R43). In this proposal, we seek to accelerate transitions to clinical trials with a new small diameter silk graft for blood vessels. We will focus on control of blood-silk biomaterial interactions by using a multifunctional approach for spatial regulation of material properties, biochemical functionalization, and drug loading and release from the silk grafts. This proposal addresses a critical outstanding clinical need for small diameter vascular grafts for coronary or femoral artery bypass in patients with advanced vascular disease and no suitable blood vessels to harvest, the common clinical practice. If vessels can be engineered to serve the function of native vessels, while also slowly fully integrating into the host vasculature, this would revolutionize small blood vessel surgery, reduce second site morbidity, and improve patient recovery. To address this challenge, we propose the development of a "cell-instructive" biomaterial graft using a natural biopolymer that is FDA approved, silk fibroin, combined with bioactive molecules to control blood protein and biomaterial interactions as well as recruit and guide host cells towards the formation of a blood vessel in situ. We specifically propose to develop acellular silk grafts designed to: (a) control graft protein and cellular interactions by biochemically functionalizing or loading the grafts with antithrombogenic drugs, (b) guide the formation of confluent endothelium by recruiting host cells (to provide long-term non-thrombogenicity), (c) mediate the migration and proliferation of host smooth muscle cells forming the vascular wall, and (d) degrade slowly and remodel over time for full integration and vascular function. The grafts will be studied in vitro (in tissue engineering studies with cells) and in vivo (artery replacement in a small animal model) in order to correlate protein and cellular responses to the graft parameters and optimize their design. PUBLIC HEALTH RELEVANCE: Improved options to repair and restore blood vessel function, particularly small diameter vessels, would have a significant positive impact human health. Cardiovascular disease remains a leading cause of death in the United States and coronary bypass surgery is common. The proposed approach in this program would overcome the limitations present with current coronary bypass surgeries and offer a new strategy for full regeneration of native blood vessels. The same technology has potential impact in a broader range of coatings for other medical devices, offering a range of benefits to human health and well being

描述（由申请人提供）：本申请标题为“多功能抗血栓蚕丝移植物的开发、表征和应用”，是对申请请求（RFA）编号RFA-OD- 09-009的回复：恢复法案有限竞争：小型企业加速创新研究催化剂奖（R43）。在这项提案中，我们寻求加速向临床试验的过渡，使用新的小直径血管丝移植物。我们将专注于通过使用多功能方法对材料特性、生化功能化以及丝移植物的药物装载和释放进行空间调节来控制血-丝生物材料相互作用。 该提案解决了在患有晚期血管疾病且没有合适血管可供采集的患者中进行冠状动脉或股动脉旁路手术的小直径血管移植物的关键突出临床需求，这是常见的临床实践。如果血管可以被设计成提供天然血管的功能，同时也慢慢地完全整合到宿主血管系统中，这将彻底改变小血管手术，减少第二部位发病率，并改善患者恢复。为了应对这一挑战，我们提出了一种“细胞指导”的生物材料移植物的发展，使用FDA批准的天然生物聚合物，丝素蛋白，结合生物活性分子来控制血液蛋白和生物材料的相互作用，以及招募和引导宿主细胞形成血管原位。我们特别建议开发脱细胞蚕丝移植物，旨在：（a）通过生物化学功能化或用抗血栓形成药物装载移植物来控制移植物蛋白和细胞相互作用，（B）通过募集宿主细胞来引导汇合内皮的形成（以提供长期的非血栓形成性），（c）介导形成血管壁的宿主平滑肌细胞的迁移和增殖，和（d）缓慢降解并随时间重塑以实现完全整合和血管功能。移植物将在体外（细胞组织工程研究）和体内（小动物模型中的动脉置换）进行研究，以将蛋白质和细胞反应与移植物参数相关联并优化其设计。 公共卫生相关性：改善修复和恢复血管功能的选择，特别是小直径血管，将对人类健康产生重大的积极影响。心血管疾病仍然是美国的主要死亡原因，冠状动脉搭桥手术很常见。该计划中提出的方法将克服目前冠状动脉搭桥手术的局限性，并为自体血管的完全再生提供一种新的策略。同样的技术对其他医疗器械的更广泛涂层具有潜在影响，为人类健康和福祉提供了一系列益处