ANALYTICAL AND EXPERIMENTAL STUDY OF ARTICULAR CARTILAGE GROWTH IN VITRO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 关节软骨在几十年中经历了高水平的生物力学应力[1]，并且在许多情况下可以耐受多年的重复负荷。然而，软骨损伤和退化经常发生在创伤性关节损伤和特定部位（如膝盖和臀部）的年龄增长。治疗退化软骨的一种有前景的临床策略是体外构建体的组织工程（即，体外）然后将它们植入体内缺损（即，在体内），然后发生成熟。与组织生物力学相关的一些特定设计目标的实现，如分子含量和机械性能，可能是开发持续成功的软骨缺损修复策略的关键。本文提出的研究的长期目标是开发一种分析性软骨生长模型（CGM），该模型可作为组织工程构建体体外生长的范例。这项工作的目标是开发一个基于分子的纳米力学模型的软骨蛋白多糖的压缩。将使用分子力学方法来获得硫酸软骨素糖胺聚糖（GAG）和聚集蛋白聚糖在压缩中的应力-应变行为，这被认为是关节软骨抗压缩性的主要原因。商业软件Gromacs 3.3将用于分析不同生理位置的GAG在水中的参考构型。参考配置对应于在无负载下导致势能最小的优化配置，然后施加渐进拉伸，针对该渐进拉伸，计算每个步骤的最小能量配置。通过计算能量相对于GAG长度的二阶导数（相对于分子量归一化），从能量数据确定GAG刚度。这一目标的长期成果是软骨蛋白聚糖溶液的分子基纳米力学模型的发展和CGM中使用的有限变形本构方程的改进

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Articular cartilage experiences a high level of biomechanical stress over many decades [1] and, in many cases, can tolerate years of repetitive loading. However, cartilage damage and degeneration occur often with traumatic joint injury and advancing age at particular sites, such as the knee and hip. One promising clinical strategy for treating degenerated cartilage is tissue engineering of constructs in vitro (i.e., outside the body) followed by their implantation into defects in vivo (i.e., inside the body), after which maturation occurs. The attainment of a number of specific design goals related to tissue biomechanics, such as molecular contents and mechanical properties, are likely to be critical to the development of a consistently successful strategy for the repair of cartilage defects. The long-term goal of the research proposed here is to develop an analytical cartilage growth model (CGM) that may serve as a paradigm for the in vitro growth of tissue engineered constructs. The goal of this work is to develop a molecular-based nanomechanical model of cartilage proteoglycans in compression. Molecular mechanics methods will be used to obtain the stress-strain behavior in compression for chondroitin sulfate glycosaminoglycans (GAGs) and aggrecan, which are thought to be predominantly responsible for the compressive resistance of articular cartilage. Commercial software, Gromacs 3.3, will be used to analyze the reference configuration of the GAGs in water in different physiological positions. The reference configuration corresponds to the optimized configuration that results in a minimum of potential energy under no loading, then progressive stretches are applied for which the minimum energy configuration is calculated for each step. The GAG stiffness is determined from the energy data by calculating the second derivative of energy with respect to GAG length, normalized with respect to molecular weight. The long-term outcome of this aim is the development of molecular-based nanomechanical models of cartilage proteoglycan solutions and the refinement of the finite deformation constitutive equations used in the CGM