This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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
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