ANALYTICAL AND EXPERIMENTAL STUDY OF ARTICULAR CARTILAGE GROWTH IN VITRO

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 关节软骨经历了几十年的高水平生物力学应力[1]，在许多情况下，可以耐受数年的重复加载。然而，随着创伤性关节损伤和特定部位(如膝盖和髋关节)年龄的增加，软骨损伤和退化经常发生。一种很有前途的治疗退行性软骨的临床策略是在体外(即体外)构建组织工程，然后将其植入体内(即体内)的缺损处，之后发生成熟。一些与组织生物力学相关的特定设计目标的实现，如分子含量和力学性能，可能是开发出持续成功的软骨缺损修复策略的关键。这项研究的长期目标是开发一种分析性软骨生长模型(CGM)，该模型可以作为组织工程化构建物体外生长的范例。这项工作的目标是开发一种基于分子的软骨蛋白多糖压缩的纳米力学模型。分子力学方法将被用来获得硫酸软骨素糖胺聚糖和聚集素的压缩应力-应变行为，它们被认为是关节软骨压缩阻力的主要原因。商业软件Gromacs 3.3将用于分析水中不同生理位置的GAG的参考构型。参考构形对应于优化构形，该优化构形在无载荷下产生最小势能，然后应用渐进拉伸，其中计算每一步的最小能量构形。通过计算能量相对于Gag长度的二次导数(相对于分子量归一化)，根据能量数据确定Gag硬度。这一目标的长期成果是发展基于分子的软骨蛋白多糖溶液的纳米力学模型，并改进用于CGM的有限变形本构方程。

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