Designing a meniscal substitute through an integrated experimental computational

描述（由申请人提供）： 膝关节是C形纤维软骨盘，占据膝关节的外周，并提供许多重要的机械功能，包括关节软骨上的负荷分布和关节稳定。面对这样的机械要求，半月板可能会受损并不奇怪。不幸的是，用于治疗受损半月板的手术选择是有限的，主要是由于中央三分之二半月板的血管分布和愈合能力差。同种异体移植物植入由于感染性疾病传播的威胁、假体形状和材料特性匹配的困难以及维持细胞活力的问题而变得复杂。而骨关节炎切除术（完全或部分切除受影响的组织）是美国最常见的骨科手术，可导致骨关节炎的早期发作。提供一种经工程改造的骨替代物，使其功能与天然组织相似，可以延缓甚至避免骨关节炎的发作。 半月板替代物，无论是细胞接种的可降解支架还是合成植入物，都应该理想地有助于以天然组织的方式将载荷分布在相邻的关节软骨上，从而保护下面的关节软骨。然而，确保满足这种功能能力所需的替代品的属性尚不清楚。这部分是由于缺乏一个强大的，全面的和生理相关的模型，其中的替代品设计变量的影响，可以参数化研究。这种测试或一系列测试的缺乏使得候选支架的设计和评估不可能，阻碍了商业化的监管途径，并导致支架植入人体时几乎没有关于其在膝关节的高负荷环境中机械性能的信息。 我们的目标是在一系列患者人群中确定关节替代材料和结构特性与多种生理活动下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几何的，快速计算的模型，将使用实验验证的膝关节特定的计算模型的结果建立。我们将收集有关最显著影响自体半月板功能性能的因素的信息，并将此信息用作模板，以确定替代品应落入的设计空间，如果它们要正常工作的话。我们的目标不是设计一个替代品，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，供那些开发解决方案的修复。我们的努力将最终发展一种新的范式，用于开发和筛选任何复杂的组织替代品，无论是不可降解的植入物还是细胞接种的可降解支架，然后再开始更耗时和昂贵的动物和临床试验。

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.