Exchangeable Heart Valve for Tissue Engineering Applications

描述(申请人提供)：在美国，每年有7万名患者需要接受心脏瓣膜置换手术。这些患者可以接受由动物组织制成的生物假体，也可以接受由合成材料制成的机械瓣膜。生物假体的并发症很少，被认为是大多数患者的理想瓣膜，但最终磨损仅持续约12-15年。另一方面，机械瓣膜是因为抗凝相关的并发症，只有在患者太小而不能接受生物假体的情况下才使用。驱动机械或生物瓣膜决定的问题是再次手术的风险-人工瓣膜打算植入一次，应该持续患者的生命。为了解决再次手术死亡率的问题，VXI一直在开发一种替代方法--一种快速交换的生物假体瓣膜。这是一种由两部分组成的装置，包括一个固定在患者主动脉上的永久性“对接站”和一个可折叠的框架，该框架支撑可交换的传单集并将其插入对接站。使用微创工具或导管，可以快速、安全地进行置换，消除了大部分再次手术的风险。有了这项技术，终于有了供机械瓣膜患者使用的组织瓣。为了扩大可交换瓣膜技术的应用，VXI正在研究一项新兴技术-心脏瓣膜组织工程。这一领域的进展一直受到实验模型成本的阻碍-幼年绵羊在主动脉位置植入了组织工程瓣膜。每项实验的费用约为1.5万美元，科学家们需要最大限度地减少绵羊的数量，并最大化植入期间的持续时间。这种方法限制了可以从这类实验中获得的信息。如果动物实验使用的是可交换的瓣膜，如VXI开发的瓣膜，动物不需要牺牲。这种瓣膜可以移植、检查、重新植入或与不同的组织工程瓣膜交换，而不需要牺牲动物。因此，这项STTR建议的目标是(I)开发一种可交换瓣膜，该瓣膜可以安装由通常用于组织工程的可生物降解聚合物组成的小叶，以及(Ii)通过组织培养和机械测试来评估可交换框架内组织生长的完整性。还将进行流体动力耐久性测试，以(Iii)确保整个阀门总成没有设计缺陷。通过这个项目，VXI将开发为从事组织工程的基础科学家服务的技术。因此，VXI将继续推进人工瓣膜技术领域，进入需要为心脏瓣膜疾病患者提供创新解决方案的新领域。每年，美国有7万名患者需要接受心脏瓣膜置换手术。这些患者可以接受由动物组织或合成人造材料制成的瓣膜。组织瓣的并发症很少，被认为是大多数患者的理想瓣膜，但最终会在大约12-15年内磨损。另一方面，机械瓣膜会导致血液凝固问题，患者需要使用永久性血液稀释剂，基本上过着血友病患者的生活。促使人们做出人工瓣膜或组织瓣膜决定的问题是再次手术的风险。尽管第一次心内直视手术相对安全，但随后的手术风险要大得多。人工心脏瓣膜打算植入一次，并应持续患者的生命。为了解决再次手术并发症的问题，VXI一直在开发一种替代方法--一种快速可交换的组织瓣。这是一种由两个组件组成的装置，包括一个留在患者体内的永久性“对接站”和一个可折叠的框架，该框架支撑最终磨损的可交换组织。此可更换组件可从坞站卡入和卡出。更换瓣膜的过程可以快速安全地完成，而不需要心脏直视手术。为了扩大可交换瓣膜技术的应用，VXI正在研究一项新兴技术-心脏瓣膜组织工程。这一领域的进展一直受到动物实验成本的阻碍，在动物实验中，这种方法的可行性总是需要证明。最常用的动物模型是幼年绵羊，它通过手术植入了组织工程瓣膜的原型。6-9个月后，动物被宰杀，瓣膜被移除，并检查是否重新生长和愈合。由于每个实验的成本约为1.5万美元，包括手术在内，科学家需要最大限度地减少使用的绵羊数量，并最大化实验的持续时间。然而，这种方法限制了可以从这类实验中获得的信息。如果动物实验使用的是可交换的瓣膜，如VXI开发的瓣膜，动物不需要牺牲。这种瓣膜可以被移除、检查、重新植入或与不同的组织工程瓣膜交换，而不需要杀死动物。因此，这项STTR建议的目标是(I)开发一种可交换瓣膜，该瓣膜可以安装由通常用于组织工程的可生物降解聚合物组成的小叶，以及(Ii)通过组织培养和机械测试来评估植入可交换瓣膜框架内的组织的完整性。还将进行耐久性测试，以(Iii)确保整个阀门组件没有设计缺陷。通过这个项目，VXI将开发出有利于开发组织工程心脏瓣膜的科学家的技术。因此，VXI将继续推进心脏瓣膜技术领域，进入需要为心脏瓣膜疾病患者提供创新解决方案的新领域。

DESCRIPTION (provided by applicant): Each year, 70,000 patients in the United States need to have their diseased heart valves replaced. These patients can receive either bioprostheses made from animal tissues, or mechanical valves made from synthetic materials. Bioprostheses have few complications and are considered the ideal valve for most patients, but ultimately wear out last only about 12-15 years. Mechanical valves, on the other hand, because anticoagulation-related complications and used only if the patient is too young to receive a bioprosthesis. The issue that drives the decision for a mechanical or bioprosthetic valve is the risk of reoperation - prosthetic valves are intended to be implanted once and should last the life of the patient. To address the problem of reoperative mortality, VXI has been developing an alternative approach - a rapidly exchangeable bioprosthetic valve. It is a two-component device, consisting of a permanent "docking station" that remains affixed to the patient's aorta, and a collapsible frame that supports the exchangeable leaflet set and plugs into the docking station. Exchange can be done quickly and safely, using minimally invasive tools or catheters, eliminating most of the risk of reoperation. With this technology, there is finally a tissue valve for mechanical valve patients. In an effort to broaden the use of the exchangeable valve technology, VXI is addressing an emerging technology - heart valve tissue engineering. Progress in this field has been hampered by the cost of the experimental model - the juvenile sheep that has a tissue-engineered valve implanted in the aortic position. At about $15,000 per experiment, scientists need to minimize the number of sheep and maximize the duration of the implant period. This approach limits the information that can be obtained from such experiments. If the animal experiments were to use an exchangeable valve, such as that developed by VXI, the animal need not be sacrificed. The valve can be explanted, examined, re-implanted, or exchanged with a different tissue-engineered valve, without needing to sacrifice the animal. The objectives of this STTR proposal, therefore, are to (i) develop an exchangeable valve that can be fitted with leaflets composed biodegradable polymers typically used for tissue engineering, and (ii) evaluate the integrity of the tissue ingrowth into the exchangeable frame through tissue culture and mechanical testing. Hydrodynamic durability testing will also be done to (iii) ensure that there are no design flaws in the complete valve assembly. Through this project, VXI will develop technologies that will serve the basic scientist engaged in tissue engineering. VXI will thus continue to advance the field of prosthetic valve technologies into new areas where innovative solutions for patients with heart valve disease are needed. Each year, 70,000 patients in the United States need to have their diseased heart valves replaced. These patients can receive valves made from animal tissues, or synthetic, man- made materials. Tissue valves have few complications and are considered the ideal valve for most patients, but ultimately wear out in about 12-15 years. Mechanical valves, on the other hand, cause blood clotting problems and the patients need to be on permanent blood thinners, essentially living the life of a hemophiliac. The issue that drives the decision for a synthetic or tissue-based valve is the risk of reoperation. Although the first open- heart surgery is relatively safe, subsequent surgeries are far more risky. Artificial heart valves are intended to be implanted once and should last the life of the patient. To address the problem of reoperative complications, VXI has been developing an alternative approach - a rapidly exchangeable tissue valve. It is a two-component device, consisting of a permanent "docking station" that remains in the patient, and a collapsible frame that supports the exchangeable tissue that ultimately wears out. This exchangeable component snaps in and out from the docking station. The procedure to exchange the valve can be done quickly and safely, without requiring open-heart surgery. In an effort to broaden the use of the exchangeable valve technology, VXI is addressing an emerging technology - heart valve tissue engineering. Progress in this field has been hampered by the cost of the animal experiments in which the feasibility of this approach always needs to be demonstrated. The most commonly used animal model is a juvenile sheep, which has prototype tissue tissue-engineered valves surgically implanted. After 6- 9 months, the animal is killed and the valve removed and examined for re-growth and healing. Since each experiment costs about $15,000, including the surgery, scientists need to minimize the number of sheep used and maximize the duration of the experiment. This approach, however, limits the information that can be obtained from such experiments. If the animal experiments were to use an exchangeable valve, such as that developed by VXI, the animal need not be sacrificed. The valve can be removed, examined, re-implanted, or exchanged with a different tissue-engineered valve, without needing to kill the animal. The objectives of this STTR proposal, therefore, are to (i) develop an exchangeable valve that can be fitted with leaflets composed biodegradable polymers typically used for tissue engineering, and (ii) evaluate the integrity of the tissue in-growth into the exchangeable valve frame through tissue culture and mechanical testing. Durability testing will also be done to (iii) ensure that there are no design flaws in the complete valve assembly. Through this project, VXI will develop technologies that will benefit scientists developing tissue-engineered heart valves. VXI will thus continue to advance the field of heart valve technologies into new areas where innovative solutions for patients with heart valve disease are needed.