Nanomechanics of Cartilage Extracellular Matrix Macromolecules from Aged, Diseased, and Engineered Tissues

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The research objective of this award is to investigate the ultrastructure and biophysical properties of extracellular matrix macromolecules from aged, diseased, and engineered cartilage tissue. A suite of novel atomic force microscopy-based imaging and nanomechanical methodologies will be employed, in conjunction with traditional biochemical techniques, to carry out four specific aims. Firstly (Aim 1), the effects of age and osteoarthritic (OA) degradation on the nanomolecular architecture of human cartilage aggrecan will be quantified and compared. Secondly (Aim 2), the nanomechanical properties (e.g. equilibrium/dynamic compressive and shear properties, biomolecular self-adhesion, etc.) of the human aggrecan studied in Aim 1, will be measured, compared, and related to molecular architecture (Aim 1) as a function of the age and extent of OA degradation of the parent cartilage tissue. Thirdly (Aim 3), aggrecan synthesized by chondrocytes and marrow-derived progenitor cells undergoing chondrogenesis in vitro in tissue engineered scaffolds will be analyzed. Lastly (Aim 4), the effect of macroscopic static and dynamic compressive loading applied to tissue engineered cartilage constructs on the molecular structure-nanomechanical properties of aggrecan will be studied.This research program will elucidate the critical molecular mechanistic origins of cartilage functionality as well as the pathology of degeneration and OA disease. In addition, novel nanotechnological methodologies will be applied to cartilage tissue engineering which holds great potential for advancement towards improved treatments of congenital diseases, traumatic injuries, and degenerative processes such as aging. The diversity component of this program includes; the recruitment of underrepresented minority (URM) students at all academic levels to the research program, the development of an annual technical symposia at a URM-based science and engineering conference, participation in a 2.5 day "Future Faculty Workshop" for URM graduate students in postdocs from around the country, and outreach via membership on the advisory board for a PBS children's television show and multimedia project.