TISSUE ENGINEERED VASCULAR PROSTHESES

组织工程血管假体

• 批准号: 6182467
• 负责人: LAURA E NIKLASON
• 金额: $ 11.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182467
• 关键词: autologous transplantation; biomaterial development /preparation; biomaterial evaluation; blood vessel prosthesis; blood vessel transplantation; cell adhesion; cell growth regulation; laboratory rat; medical implant science; medical rehabilitation related tag; muscle contraction; polymers; tissue /cell culture; tissue engineering

DESCRIPTION (Adapted from the applicant's abstract) This Mentored Clinical Scientist Development Award application focuses on the development of a tissue engineered vascular prosthesis. There are 1.4 million surgical procedures performed annually in this country that require arterial prostheses. Medium to small diameter arteries, (less than six mm) when bypassed with artificial materials suffer high rates of early and late thrombosis. Vein grafts are fragile and are sometimes damaged when transplanted into the arterial system. Internal mammary arteries, which perform better than vein grafts, are useful only in the coronary circulation. To address these issues, the long term goal of this project is to develop a method for culturing autologous arteries from a small biopsy of the patient's own tissue. The patient's own cells would be seeded onto tubular biocompatible polymer scaffolds and grown in vitro to form complete blood vessels, with inner linings of endothelial cells and outer smooth muscle cell walls. While the feasibility of seeding and growing human and other mammalian cells on biocompatible polymers has been demonstrated, even in clinical trials, the cell-polymer system for the growth of blood vessels has only begun to be studied. While the proposed project is an extensive one and its completion may require longer than the five years applicable to this award, the applicant feels it is important to present a comprehensive approach to this challenging but important problem. The first goal of this project will be to culture endothelial and smooth muscle cells on biocompatible, biodegradable polymer scaffolds to form a vascular tissue. This will involve selection of the optimum polymer and processing techniques encourage cell adhesion and replication, optimization of cell seeding onto the polymer substrates, and the development of techniques to culture the cell-polymer constructs under conditions of intra-luminal fluid flow, to mimic in vivo vascular conditions. The second goal of this project will be to determine whether cultured vascular tissues will exhibit adequate biomechanical and physiologic properties for use in the arterial system in vivo. This will involve, specifically, the determination of the physical and mechanical characteristics of the cultured tissues, characterization of the smooth muscle layer for contractile phenotype and isometric response to vasoactive agents, and characterization of the endothelial cell layer by assaying the expression of basic cell functions and adhesion molecules on the cell surface. Provided the vessels display adequate biomechanical and physiologic characteristics, animal implant studies will be performed.

描述 （改编自申请人摘要）本指导临床科学家 发展奖的申请重点是组织的发展 人造血管 有140万例外科手术 每年都有需要动脉假体的手术 介质 小直径动脉（小于6 mm），当使用人工血管旁路时 材料的早期和晚期血栓形成率很高。 静脉移植是 移植到动脉后有时会受损 系统 内乳动脉，比静脉移植更好， 仅在冠状循环中有用。 为了解决这些问题， 该项目的长期目标是开发一种培养 自体动脉从一个小活检的病人自己的组织。 的 患者自身的细胞将被接种到管状生物相容性聚合物上 支架，并在体外生长，形成完整的血管， 内皮细胞和外平滑肌细胞壁的衬里。 而 将人类和其他哺乳动物细胞接种和生长在 生物相容性聚合物已经被证明，即使在临床试验中， 用于血管生长的细胞聚合物系统才刚刚开始被 研究了 虽然拟议的项目是一个广泛的，其完成 可能需要超过适用于本奖项的五年， 申请人认为提出一个全面的方法是很重要的， 具有挑战性但重要的问题。 该项目的第一个目标将是 为了在生物相容性， 可生物降解的聚合物支架以形成血管组织。 这将 包括选择最佳的聚合物和加工技术， 细胞粘附和复制，细胞接种到聚合物上的优化 基质，以及培养细胞聚合物的技术的发展 在腔内流体流动的条件下构建，以模拟体内 血管状况 该项目的第二个目标是确定 培养的血管组织是否会表现出足够的生物力学和 用于体内动脉系统的生理特性。 这将 具体来说，涉及到确定物理和机械 培养组织的特征，光滑组织的表征， 肌层对血管活性物质的收缩表型和等长反应 试剂，并通过测定内皮细胞层的特性， 细胞基本功能和细胞上粘附分子的表达 面 如果血管显示出足够的生物力学和 生理特性，将进行动物植入研究。

项目成果

Advances in tissue engineering of blood vessels and other tissues.

• DOI: 10.1016/s0966-3274(97)80013-5
• 发表时间: 1997-12
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: Laura E. Niklason;Robert Langer

Prospects for organ and tissue replacement.

• DOI: 10.1001/jama.285.5.573
• 发表时间: 2001-02
• 期刊: JAMA
• 作者: Laura E. Niklason;Robert Langer

Engineering porcine arteries: effects of scaffold modification.

工程猪动脉：支架修饰的影响。

• DOI: 10.1002/jbm.a.10603
• 发表时间: 2003
• 期刊: Journal of biomedical materials research. Part A.
• 作者: Prabhakar,Vikas;Grinstaff,MarkW;Alarcon,Javier;Knors,Chris;Solan,AmyK;Niklason,LauraE
• 通讯作者: Niklason,LauraE