Anti-fibrotic Coatings for Rapidly Exchangeable Bioprosthetic Heart Valve

用于快速更换生物人工心脏瓣膜的抗纤维化涂层

• 批准号: 7481744
• 负责人: Ivan Vesely
• 金额: $ 128.33万
• 依托单位: VALVEXCHANGE, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7481744
• 关键词: Abate; Address; Adhesions; Age; Age-Years; Animal Model; Animals; Anticoagulants; Anticoagulation; Apex of the Heart; Autopsy; Biocompatible Materials; Bioprosthesis device; Bypass; Carbon; Cardiac; Cardiac Surgery procedures; Cardiac conduction system; Catheters; Chromium; Chronic; Clinical; Clip; Cobalt; Control Groups; Coronary artery; Devices; Disruption; Docking; Excision; Facility Construction Funding Category; Fibrosis; Figs - dietary; Generations; Gold; Grant; Hand; Healed; Heart; Heart Valves; Hemorrhage; Hour; Immune response; Implant; Incidence; Invasive; Life; Life Style; Manufacturer Name; Marketing; Measurement; Measures; Mechanics; Medical Device; Metals; Modeling; Molybdenum; Morbidity - disease rate; Natural graphite; Numbers; Operative Surgical Procedures; Partner in relationship; Patients; Pericardial body location; Phase; Phase I Clinical Trials; Plant Roots; Positioning Attribute; Principal Investigator; Procedures; Prosthesis; Quality of life; Repeat Surgery; Research Personnel; Risk; Sheep; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Specimen; Sports; Standards of Weights and Measures; Stearates; Steel; Stroke; Surface; Surgeon; Surgical incisions; Surgical sutures; System; Testing; Thromboembolism; Thrombosis; Time; Tissues; United States; Welding; animal tissue; base; concept; design; healing; implantation; improved; mortality; novel; older patient; pressure; prevent; programs; prototype; pyrolytic carbon; research study; response

DESCRIPTION (provided by applicant): Each year, over 100,000 patients in the United States need to have their diseased heart valves replaced with artificial devices. Although bioprostheses, valves made from animal tissues, are considered ideal for most patients, they wear out in about 15 years. They are thus used primarily in the elderly patient who is not expected to outlive the valve. Younger patients receive mechanical valves that are more durable, but require chronic administration of blood thinners. This makes participation in most sports impossible and exposes the patient to increased risk for fatal bleeds and strokes. ValveXchange, Inc. ( VXI ) is a medical device company developing a two-part heart valve consisting of a surgically implanted base and an exchangeable bioprosthetic tissue leaflet set. The VXI device is a lifetime tissue valve replacement system that does not require anticoagulation. During the first surgery, the docking station is first sewn in place and the leaflets are snapped in. This allows the surgeon to place sutures more conveniently, without risk of damaging the leaflet core. As the leaflet set begins to show signs of wear it can be exchanged rapidly, using a minimally invasive surgical or percutaneous procedure. Rapid, minimally invasive leaflet exchange dramatically reduces surgical time and eliminates the need the technically demanding and potentially dangerous re-excision of the initial prosthetic valve. As the leaflet set is exchanged, the docking station remains permanently in place so there is no disruption of the sensitive tissue of the aortic root; a vital part of the conduction system of the heart and the origin of the coronary arteries. VXI has successfully completed two Phase I projects. In the first, VXI developed prototype exchangeable valves and demonstrated their technical feasibility in an animal model by exchanging a valve in 23 seconds. In the second, VXI investigated the ability of anti-adhesion coatings to abate fibrotic overgrowth in the hyper-fibrotic sheep model. In this Phase II application we propose to implement our novel anti-adhesion coatings in a chronic sheep model and investigate the long-term host response of the rapidly exchangeable valve. We will fabricate 8 valves each from bare cobalt-chrome, cobalt-chrome treated with a stearate coating, and from pyrolitic carbon. Both stearate and pyrolitic carbon have been shown to repel fibrotic overgrowth in the Phase I study. A control group will make use of the gold standard Edwards pericardial valve. After 3 and 5 months of implantation, the leaflet sets will be exchanged using an open surgical procedure in which the reduced time on cardiac bypass will be documented, and the degree of fibrotic overgrowth measured. Detailed measurements of fibrotic overgrowth and incidence of thromboembolism will be examined at necropsy. This revised resubmission now includes more specific criteria upon which to base a redesign of the valve and the anti-fibrotic coatings. Each year, over 100,000 patients in the United States need to have their diseased heart valves replaced with artificial devices. Although artificial heart valves made from materials of animal origin are considered ideal for most patients, they wear out in about 15 years. They are thus used primarily in the elderly patient who is not expected to outlive the valve. Younger patients receive mechanical valves, made from metals and graphite-like materials. Although these types of valves will last the life of the patient, they require the patient to be on blood thinners. This makes participation in most sports impossible and exposes the patient to increased risk for fatal bleeds and strokes. ValveXchange, Inc. ( VXI ) is a medical device company developing a two-part heart valve consisting of a surgically implanted base and an exchangeable animal tissue-based leaflet set. The VXI device is a lifetime tissue valve replacement system that does not require the patient to be on blood thinners. During the first surgery, the docking station is first sewn in place and the leaflets are snapped in. This allows the surgeon to place his stitches more conveniently, without risk of damaging the leaflet core. As the leaflet set begins to show signs of wear it can be exchanged rapidly, using a minimally invasive surgical or catheter-based procedure. Rapid, minimally invasive leaflet exchange dramatically reduces surgical time and eliminates the need the technically demanding and potentially dangerous re-excision of the initial valve. As the leaflet set is exchanged, the docking station remains permanently in place, so there is no disruption of the sensitive tissue of the aortic root a vital part of the conduction system of the heart and the origin of the coronary arteries. VXI has successfully completed two Phase I projects. In the first, VXI developed prototype exchangeable valves and demonstrated their technical feasibility in an animal model by exchanging a valve in 23 seconds. In the second, VXI investigated the ability of anti-adhesion coatings to abate tissue overgrowth in the sheep, an animal known to generate a prolific healing response. In this Phase II application we propose to implement our novel anti-adhesion coatings in the sheep model and investigate the long-term response of the host to the rapidly exchangeable valve. We will fabricate 24 valves with the mating surfaces between the docking station and the leaflet set made from biocompatible materials, such as steel treated with a number of anti-adhesion coatings shown to repel tissue overgrowth in the Phase I study. A control group consisting of a commercially available valve from a well-established manufacturer will also be used. After 3 and 5 months of implantation, the leaflet sets will be exchanged using an open surgical procedure in which the reduced time on cardiac bypass will be documented, and the degree of tissue overgrowth measured. Detailed measurements of fibrotic overgrowth and incidence of thromboembolism will be examined at necropsy. This revised resubmission adds additional criteria on which redesign of the valve and the anti-adhesion coatings may be necessary.

描述（由申请人提供）：每年，美国超过100,000名患者需要将患病的心脏瓣膜替换为人造设备。尽管生物植物（由动物组织制成的瓣膜）被认为是大多数患者的理想选择，但它们在大约15年内磨损。因此，它们主要用于不预计阀门的老年患者。年轻的患者会收到更耐用的机械瓣膜，但需要长期给予血液稀释剂。这使参加大多数运动的参与不可能，并使患者暴露于增加致命性出血和中风的风险。 ValvexChange，Inc。（VXI）是一家医疗器械公司，开发了由手术植入的碱和可交换的生物假体组织套件组成的两部分心脏阀。 VXI设备是寿命组织阀置换系统，不需要抗凝系统。在第一次手术期间，首先缝制了对接站，并将传单塞进去。这使外科医生可以更方便地放置缝合线，而不会损坏传单核心。当传单套件开始显示磨损的迹象时，可以使用微创手术或经皮手术迅速交换它。快速，微创的传单交换大大减少了手术时间，并消除了对初始假体阀门的技术要求和潜在危险的重新验证的需求。当交换传单时，对接站永久停留在适当的位置，因此主动脉根的敏感组织没有中断。心脏传导系统的重要部分和冠状动脉的起源。 VXI已成功完成了两个I期项目。首先，VXI开发了可交换的原型，并通过在23秒内交换阀门在动物模型中证明了它们的技术可行性。在第二个中，VXI研究了抗粘附涂层减轻纤维化绵羊模型中纤维化过度生长的能力。在此II阶段应用中，我们建议在慢性绵羊模型中实施我们的新型抗粘附涂层，并研究快速可交换阀的长期宿主反应。 我们将用硬脂酸涂层和碳酸碳处理的碳糊状，钴染色物和碳碳制造8个阀门。在I期研究中，硬脂酸酯和热素碳都已证明可以排除纤维化的过度生长。对照组将利用金标准爱德华兹心包阀。经过3个月和5个月的植入后，将使用开放的手术程序交换传单，其中将记录减少心脏旁路时间的时间，并测量纤维化过度生长的程度。将在尸检时检查纤维化过度生长和血栓栓塞发生率的详细测量。现在，此修订后的重新提交包括更具体的标准，以重新设计阀门和抗纤维化涂层。每年，美国超过100,000名患者需要将患病的心脏瓣膜替换为人造设备。尽管由动物起源材料制成的人造心脏瓣膜被认为是大多数患者的理想选择，但它们在大约15年内磨损。因此，它们主要用于不预计阀门的老年患者。年轻的患者接收由金属和石墨样材料制成的机械瓣膜。尽管这些类型的瓣膜将持续患者的寿命，但他们要求患者使用血液稀释剂。这使参加大多数运动的参与不可能，并使患者暴露于增加致命性出血和中风的风险。 ValvexChange，Inc。（VXI）是一家医疗器械公司，开发了由手术植入的基部和可交换动物组织的小叶套装组成的两部分心脏阀。 VXI设备是终生组织阀门的替代系统，不需要患者使用血液稀释剂。在第一次手术期间，首先缝制了对接站，并将传单塞进去。这使外科医生可以更方便地将其针迹放置，而不会损坏传单芯的风险。当传单套件开始显示磨损的迹象时，它可以使用最小的侵入性手术或基于导管的程序来迅速交换。快速，微创的传单交换大大减少了手术时间，并消除了初始阀门的技术要求和潜在危险的重新验证的需求。当交换传单时，对接站永久保留在适当的位置，因此主动脉根的敏感组织不会破坏心脏的传导系统的重要部分和冠状动脉的起源。 VXI已成功完成了两个I期项目。首先，VXI开发了可交换的原型，并通过在23秒内交换阀门在动物模型中证明了它们的技术可行性。在第二个中，VXI研究了抗粘附涂层减轻绵羊组织过度生长的能力，绵羊是一种已知的动物，可产生多产的愈合反应。在此II阶段的应用中，我们建议在绵羊模型中实施我们的新型抗粘附涂层，并研究宿主对快速可交换阀的长期响应。 我们将在对接站和由生物相容性材料制成的传单之间制造24个阀门，例如在第一阶段研究中用许多抗粘附涂层处理的钢材料，这些材料用许多抗粘附涂层处理。还将使用由来自建立良好制造商的市售阀组成的对照组。经过3个月和5个月的植入后，将使用开放的手术程序交换传单，其中将记录减少心脏旁路时间的时间，并测量组织过度生长的程度。将在尸检时检查纤维化过度生长和血栓栓塞发生率的详细测量。此修订后的重新提取添加了其他标准，可能需要在该标准上重新设计阀门和抗粘附涂层。