Designing a meniscal substitute through an integrated experimental computational

描述(由申请人提供)： 半月板是占据膝关节周围的C形纤维软骨盘，具有许多重要的机械功能，包括跨关节软骨的载荷分配和关节稳定。面对这样的机械要求，半月板受损也就不足为奇了。不幸的是，治疗半月板损伤的手术选择有限，主要是由于半月板中央三分之二的血管和愈合能力较差。同种异体移植面临传染病传播的威胁，半月板形状和材料特性难以匹配，以及维持细胞活力的问题。而半月板切除(完全或部分切除受影响的组织)是美国最常见的整形外科手术，会导致骨关节炎的早期发作。提供一种半月板替代物可以延缓甚至避免骨关节炎的发生。半月板替代物，无论是细胞种植的可降解支架还是合成植入物，理想的情况下都应该有助于以天然组织的方式在邻近的关节软骨中分配载荷，从而保护潜在的关节软骨。然而，确保满足这一功能能力所需的替代品的性质尚不清楚。这在一定程度上是由于缺乏一个健壮的、全面的和生理上相关的模型，在该模型中可以对替代设计变量的影响进行参数研究。缺乏这样的测试或一系列测试，使候选支架的设计和评估变得不可能，阻碍了商业化的监管途径，并导致支架被植入人体，几乎没有关于其在膝关节高负荷环境中机械执行能力的信息。我们的目标是确定半月板替代材料与多种生理活动下的结构特性和关节接触力学之间的关系。实现这一目标所需的框架的主要元素是一个基于统计的、可快速计算的插值器，该插值器将使用实验验证的膝关节特定计算模型的结果来构建。我们将收集有关对自然半月板的功能性能影响最显著的因素的信息，并将这些信息用作模板，以确定如果替代品要发挥适当的功能，它们应该属于哪个设计空间。我们的目标不是设计半月板替代物；相反，我们将证明我们的方法可以建立一个可行的设计空间，供那些开发半月板修复解决方案的人使用。我们的努力最终将在开发和筛选任何复杂的组织替代品方面达到顶峰，无论是不可降解的植入物还是细胞种子的可降解支架，然后再启动更耗时和昂贵的动物和临床试验。 公共卫生相关性： 我们的目标是确定半月板材料和结构特性之间的关系，以及在多种生理活动下的关节接触力学。实现这一目标所需要的框架的主要元素是一个基于统计的、可快速计算的插值器，该插值器将使用实验验证的完整和半月板替代膝关节的计算模型的结果来构建。我们的方法将作为快速评估和设计功能替代物的工具，并为开发和筛选任何复杂的组织替代物提供新的范例，无论是不可降解的植入物还是细胞种植的可降解支架。

DESCRIPTION (provided by applicant): The menisci are C-shaped fibrocartilage disks that occupy the periphery of the knee joint and serve a number of significant mechanical functions including load distribution across articular cartilage, and joint stabilization. In the face of such mechanical demands, it is not surprising that the meniscus can become damaged. Unfortunately, surgical options for the treatment of damaged menisci are limited, primarily due to the poor vascularity and healing capacity of the central two thirds of the meniscus. Allograft implantation is complicated by the threat of transmission of infectious diseases, the difficulty of matching meniscal shape and material properties, and problems with maintaining cell viability. While meniscectomy (the complete or partial removal of the affected tissue) which is the most common orthopedic procedure performed in the United States can lead to the early onset of osteoarthritis. Providing a meniscal substitute engineered to function much in the way of the native tissue could delay or even avoid the onset of osteoarthritis. Meniscal substitutes, whether cell-seeded degradable scaffolds or synthetic implants, should ideally help to distribute loads across adjacent articular cartilage much in the way of the native tissue, thereby protecting the underlying articular cartilage. However, the properties of a substitute that are required to ensure that this functional capability is met are unclear. This is caused in part by the absence of a robust, comprehensive and physiologically relevant model within which the effect of substitute design variables can be parametrically studied. This lack of such a test, or series of tests, makes the design and evaluation of candidate scaffolds impossible, retards the regulatory pathway to commercialization, and leads to a situation where scaffolds are implanted in humans with little information about their ability to perform mechanically in the highly-loaded environment of the knee joint. Our goal is to define the relationship between meniscal substitute material and structural properties and joint contact mechanics under multiple physiological activities across a range of patient populations. The main element of the framework required to achieve this goal is a statistically-based, rapidly computable interpolator that will be built using results from experimentally-validated knee specific computational models. We will gather information about factors that most markedly affect the functional performance of the native meniscus and use this information as a template to identify the design space into which substitutes should fall if they are to function appropriately. Our goal is not to design a meniscal substitute; rather, we will demonstrate that our approach can establish a workable design space for use by those developing solutions for meniscal repair. Our efforts will culminate in the development of a new paradigm for the development and screening of any complicated tissue substitute, whether a non-degradable implant or a cell-seeded degradable scaffold prior to initiating more time consuming and costly animal and clinical trials. PUBLIC HEALTH RELEVANCE: Our goal is to define the relationship between meniscal material and structural properties and joint contact mechanics under multiple physiological activities across a range of patient populations. The main element of the framework required to achieve this goal is a statistically-based, rapidly computable interpolator that will be built using results from experimentally-validated computational models of the intact and meniscal substituted knee. Our approach will serve as a tool for rapid evaluation and design of functional substitutes and provide a new paradigm for the development and screening of any complicated tissue substitute, whether a non- degradable implant or a cell-seeded degradable scaffold.