Toward Tissue Engineering of the Knee Meniscus

膝关节半月板组织工程

• 批准号: 7169267
• 负责人: Kyriacos A Athanasiou
• 金额: $ 23.71万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-10 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169267
• 关键词: Toward; Tissue; Engineering; Knee; Meniscus

The application's long-term objective is to use a cogent and comprehensive tissue engineering approach to successfully address meniscus regeneration, which remains one of the most elusive problems in musculoskeletal medicine. The study's main hypothesis is that the meniscus can be regenerated by a series of steps that involve the use of a scaffold with bioactive agents, cells, a bioreactor, mechanical stimuli, and an animal model. To test this hypothesis, we propose the following specific aims: 1) To design, fabricate, and characterize meniscus-specific biodegradable scaffolds. 2) To engineer the meniscus. 3) To test the meniscus in an animal model. The methodology involves an analysis and a synthesis phase: In the analysis phase, topographical and spatial properties of the meniscus will be identified using biomechanics, biochemistry, ultrastructural methods, and cell culture. The objective is to define 'gold standard' properties against which the properties of the regenerated meniscus will be compared. In the synthesis phase, fibrochondrocytes will be seeded onto meniscus-specific scaffolds and exposed to mechanical forces. The scaffolds, made of poly(propylene fumarate-co-ethylene glycol), are designed to be bioabsorbable, biocompatible, have mechanical integrity, allow for directed attachment of cells through the use of the GRGD peptide, and provide biosynthetic signals through the use of a growth factor. A hydrodynamic focusing bioreactor, operating in a low-shear environment, will then be used to enhance nutrient transport and to modulate mechanical signals. Furthermore, the effects of hydrostatic pressure and direct compression/tension will also be examined using custom-made instruments. At various time points, the properties of the engineered constructs will be quantified and compared to native tissue properties. The tissue engineered constructs will then be implanted in rabbits to evaluate the in vivo functional characteristics of the new meniscus. The clinical significance of the approach described in this proposal is enormous, since meniscal problems continue to be some of the most vexing in orthopaedics.

该申请的长期目标是使用令人信服的和全面的组织工程方法， 成功地解决半月板再生，这仍然是最难以捉摸的问题之一， 肌肉骨骼医学这项研究的主要假设是，半月板可以通过一系列 包括使用具有生物活性剂、细胞、生物反应器、机械刺激和生物活性剂的支架的步骤， 动物模型为了验证这一假设，我们提出了以下具体目标：1）设计，制造， 描述了一种特定的生物可降解支架。2)去制造弯月面。3)为了测试半月板 在动物模型中。该方法包括分析和综合阶段：在分析阶段， 将使用生物力学，生物化学， 超微结构方法和细胞培养。目标是定义“黄金标准”属性， 将比较再生弯月面的特性。在合成阶段，纤维软骨细胞将 将其接种到拟南芥特异性支架上并暴露于机械力。这些脚手架是由 聚（丙二醇酯-共-乙二醇）被设计为生物可吸收的、生物相容的，具有 机械完整性，允许通过使用GRGD肽直接附着细胞，并提供 生物合成信号通过使用生长因子。一种流体动力聚焦生物反应器，其在一种生物反应器中操作， 低剪切环境，然后将用于增强养分运输和调制机械信号。 此外，静水压力和直接压缩/拉伸的影响也将使用 定制的仪器。在不同的时间点，工程化构建体的性质将被改变。 量化并与天然组织性质进行比较。然后将组织工程构建物植入 以评价新半月板的体内功能特征。的临床意义 这一建议中所描述的方法是巨大的，因为军事问题仍然是 在整形外科中最令人烦恼的。