Exchangeable Heart Valve for Tissue Engineering Applications

用于组织工程应用的可更换心脏瓣膜

• 批准号: 7261822
• 负责人: Ivan Vesely
• 金额: $ 24.79万
• 依托单位: VALVEXCHANGE, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7261822
• 关键词: Address; Adolescent; Adult; Age; Animal Experiments; Animal Model; Animals; Anticoagulants; Anticoagulation; Aorta; Area; Award; Bioprosthesis device; Blood Clot; Blood coagulation; Cardiac Surgery procedures; Catheters; Clinical; Costs and Benefits; Devices; Docking; Emerging Technologies; Ensure; Experimental Models; Figs - dietary; Funding; Generations; Growth; Hand; Healed; Heart; Heart Valve Diseases; Heart Valves; Hour; Implant; Invasive; Laboratories; Legal patent; Life; Marketing; Mechanics; Modeling; Morbidity - disease rate; Mullerian duct inhibiting substance; Numbers; Operative Surgical Procedures; Patients; Physiology; Positioning Attribute; Principal Investigator; Procedures; Process; Prosthesis; Pump; Quality of life; Repeat Surgery; Research Personnel; Risk; Scientist; Sheep; Small Business Technology Transfer Research; Solutions; Staging; Surgical sutures; System; Technology; Testing; Time; Tissue Engineering; Tissues; Trademark; United States; United States National Institutes of Health; animal tissue; base; biodegradable polymer; cost; design; healing; innovation; killings; man; mortality; older patient; programs; prototype; research study; success; tissue culture; tool

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.

描述（由申请人提供）：每年，美国有70,000名患者需要更换患病的心脏瓣膜。这些患者可以接受由动物组织制成的生物植物，或者可以接受由合成材料制成的机械瓣膜。生物植物的并发症很少，对于大多数患者而言，被认为是理想的瓣膜，但最终仅持续约12-15年。另一方面，机械瓣膜是因为与抗凝相关的并发症，并且仅当患者太年轻而无法接受生物繁殖时才使用。推动机械或生物假体阀门决定的问题是重新手术的风险 - 假肢阀旨在植入一次，并应持续患者的寿命。为了解决重新手术死亡率的问题，VXI一直在开发一种替代方法 - 一种快速交换的生物假体阀。它是一种两组分的设备，由一个永久性的“对接站”组成，该设备仍固定在患者主动脉上，并且可覆盖的框架支持可交换的传单套装并插入对接站。可以使用微创工具或导管快速安全地进行交换，从而消除了重新手术的大部分风险。有了这项技术，最终有一个用于机械瓣膜患者的组织阀。为了扩大可交换阀技术的使用，VXI正在解决新兴技术 - 心脏瓣膜组织工程。该领域的进展受到实验模型的成本的阻碍 - 在主动脉位置植入的组织工程瓣膜的少年绵羊。每次实验约15,000美元，科学家需要最大程度地减少绵羊的数量，并最大限度地提高植入期的持续时间。这种方法限制了可以从此类实验中获得的信息。如果动物实验是使用可交换阀（例如由VXI开发的阀），则无需牺牲动物。可以在不需要牺牲动物的无需牺牲的动物的情况下，可以将瓣膜饲养，检查，重新插入或与不同的组织工程阀交换。因此，该STTR提案的目标是（i）开发一个可兑换的阀，该阀可与通常用于组织工程的小叶组成的小叶组成的小叶，以及（ii）通过组织培养和机械测试评估组织向内生长的完整性。流体动力耐用性测试也将进行（iii）确保完整阀组件中没有设计缺陷。通过该项目，VXI将开发技术，这些技术将为从事组织工程的基础科学家服务。因此，VXI将继续将假肢技术的领域推向新领域，其中需要为心脏瓣膜疾病的患者进行创新的解决方案。每年，美国有70,000名患者需要更换患病的心脏瓣膜。这些患者可以接收由动物组织制成的瓣膜或合成的人造材料。组织阀的并发症很少，被认为是大多数患者的理想瓣膜，但最终在大约12 - 15年的时间内磨损。另一方面，机械瓣会导致血液凝结问题，并且患者需要使用永久性血液稀释剂，实质上是过着血友病的生命。推动合成或基于组织的阀门决定的问题是重新手术的风险。尽管第一次开心手术相对安全，但随后的手术更具风险。人造心脏瓣膜旨在植入一次，应持续患者的寿命。为了解决重新术并发症的问题，VXI一直在开发一种替代方法 - 一种迅速可交换的组织阀。它是一种两组式设备，由保留在患者中的永久性“对接站”组成，并且可折叠的框架支持最终磨损的可交换组织。此可交换组件从扩展坞进出。可以快速，安全地进行交换阀的程序，而无需开心手术。为了扩大可交换阀技术的使用，VXI正在解决新兴技术 - 心脏瓣膜组织工程。该领域的进展受到动物实验的成本的阻碍，在这种实验的成本中，这种方法的可行性总是需要证明。最常用的动物模型是少年绵羊，该绵羊具有手术植入原型组织组织工程瓣膜的原型绵羊。 6-9个月后，该动物被杀死，阀门去除并检查了重新生长和愈合。由于每个实验的费用约为15,000美元，包括手术，因此科学家需要最大程度地减少所用绵羊的数量并最大化实验持续时间。但是，这种方法限制了可以从此类实验中获得的信息。如果动物实验是使用可交换阀（例如由VXI开发的阀），则无需牺牲动物。可以将阀门去除，检查，重新插入或与不同的组织工程瓣膜交换，而无需杀死动物。因此，该STTR提案的目标是（i）开发一个可兑换的阀，该阀可与通常用于组织工程的小叶组成的小叶组成的小叶，以及（ii）通过组织培养和机械测试评估组织内生长的完整性。耐用性测试也将进行（iii）确保完整阀组件中没有设计缺陷。通过该项目，VXI将开发技术，这些技术将使科学家受益于开发组织设计的心脏瓣膜。因此，VXI将继续将心脏瓣膜技术领域推进到需要心脏瓣膜疾病患者的创新解决方案的新领域。