A Composite Tissue-engineered Aortic Valve Prosthesis

复合材料组织工程主动脉瓣假体

• 批准号: 7492500
• 负责人: Ivan Vesely
• 金额: $ 9.95万
• 依托单位: VALVEXCHANGE, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492500
• 关键词: adhesions; aortic valve; bioengineering /biomedical engineering; biomaterial development /preparation; blood vessel prosthesis; cardiovascular prosthesis; collagen; confocal scanning microscopy; elastin; fibrin; hyaluronate; immunocytochemistry; laboratory rat; medical implant science; mucopolysaccharides; newborn animals; scanning electron microscopy; tissue /cell culture; tissue engineering; transmission electron microscopy

DESCRIPTION (provided by applicant): Aortic valve disease is treated by replacing the diseased valve with either a mechanical or an animal tissue-based artificial heart valve. Unfortunately, neither device can provide good quality of life. Tissue engineering technologies offer the promise of a limitless supply of living tissues, such as replacement heart valves. The conventional approach to tissue engineering involves seeding cells on a biodegradable matrix, implanting it into the patient, and expecting a new valve to regrow as the matrix slowly degrades. Thus far, this approach has not been very successful because cardiovascular tissues are complex and have a low capacity for self-repair. We have been working on an alternative approach that we think is more appropriate for the aortic valve - the fabrication of the entire leaflet microstructure in vitro from the appropriate matrix molecules. We have been able to fabricate (i) collagen fiber bundles, both straight and branched, (ii) elastin tubes and sheets, and (iii) a viscoelastic glycosaminoglycan (GAG) matrix. Such an approach to tissue engineering (i) does not require regrowth of morphologically complex tissues, (ii) provides a matrix that can withstand cardiac loads immediately upon implantation, and (iii) can be designed and fabricated using conventional engineering principles. The GAG matrix is based on divinylsulfone-crosslinked hyaluronan (hylan), the collagen fiber bundles are fabricated using directed collagen gel shrinkage, and the elastin sheets and tubes have been grown on both the hylan and the collagen fiber bundles. Our next steps are to (i) improve the fabrication process of each of these components, (ii) improve their mechanical properties, and (iii) assemble the components to produce an aortic valve cusp with the appropriate mechanical properties. To this end we will (i) make use of dynamic cell culture to increase matrix synthesis and improve the mechanical properties of our constructs, and (ii) texturize hylan gels using UV and gamma irradiation to improve cell penetration and matrix adhesion. Once the material properties of the leaflet components are improved, they will be assembled into a composite aortic valve cusp and evaluated mechanically. Through this project, we aim to demonstrate that a tissue engineered valve cusp can be fabricated by manipulating biologic molecules in vitro using conventional biochemical and cell culture methodologies.

描述（由申请人提供）： 通过用机械或动物组织的人造心脏瓣代替患病瓣膜来治疗主动脉瓣疾病。不幸的是，这两个设备都无法提供良好的生活质量。组织工程技术提供了无限的生物组织供应，例如更换心脏瓣膜。组织工程的常规方法涉及在可生物降解的基质上播种细胞，将其植入患者，并期望随着基质缓慢降解，新阀会重新生长。到目前为止，这种方法并不是很成功，因为心血管组织很复杂，自我修复的能力较低。我们一直在研究一种我们认为更适合主动脉瓣的替代方法 - 从适当的基质分子体外制造整个传单微观结构。我们已经能够制造（i）笔直和分支的胶原纤维束，（ii）弹性蛋白管和板，以及（iii）粘弹性糖胺聚糖（GAG）矩阵。这样的组织工程方法（i）不需要形态上复杂的组织的再生，（ii）提供了一个矩阵，可以在植入后立即承受心脏负荷，并且（iii）可以使用常规工程原理设计和制造。 GAG矩阵基于Divinylsulfone-Crosslind透明质酸（Hylan），胶原纤维束使用定向的胶原凝胶收缩层制造，并且在Hylan和Hylan和胶原纤维纤维外观上都生长了弹性蛋白片和管。我们的下一步是（i）改善每个组件的制造过程，（ii）提高其机械性能，（iii）组装组件以产生具有适当机械性能的主动脉瓣膜。为此，我们将（i）利用动态细胞培养物来增加基质合成并改善构建体的机械性能，以及（ii）使用UV和Gamma辐照质地质地，以改善细胞渗透和基质粘附。一旦小叶成分的材料特性得到改善，它们将组装成复合主动脉瓣膜尖并进行机械评估。通过该项目，我们旨在证明可以通过使用常规的生化和细胞培养方法在体外操纵生物学分子来制造组织工程瓣膜尖。