Physical Forces on Cells: Effects of Applied Osmotic Loading and Direct Current Electric Fields

Cartilage and the anterior cruciate ligament (ACL) exhibit poor healing capacity when injured. Cells from these orthopaedic tissues experience continuous changes in their chemical and physical environment that may potentially modulate their properties and behavior. This dissertation is the first characterization of the applied osmotic loading and direct current electric field response of chondrocytes and ACL fibroblasts. Osmotic loading was found to influence cell material properties, calcium signaling and gene expression. Applied direct current electric fields were shown to modulate and direct cell migration as well as wound healing. These lesser-studied physical forces were also found to have differential effects on cell behavior depending on whether they were applied statically or dynamically. The combined effects of these stimuli were also investigated and alterations in extracellular osmolarity were found to modulate chondrocyte migration behavior in applied electric fields. To study the novel effects of applied dynamic osmotic loading, a custom microfluidic device was developed to apply time-varying physical and chemical stimuli to cultured cells while permitting real-time monitoring of cellular responses. The experimental systems developed over the course of this biomedical engineering dissertation provide quantitative tools that can be used to gain further insights into the cellular response to osmotic loading and electric fields that may contribute new knowledge to our understanding of mechanotransduction as well as the role of physical forces in injury and repair of orthopaedic cells.

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Year

Entry

2002

Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res. July 2002;20(4):842-848.

1977

Maroudas A, Venn M. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage, II: swelling. Ann Rheum Dis. 1977;36(5):399-406.

2001

Erickson GR, Alexopoulos LG, Guilak F. Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways. J Biomech. December 2001;34(12):1527-1535.

1989

Urban JPG, Bayliss MT. Regulation of proteoglycan synthesis rate in cartilage in vitro: influence of extracellular ionic composition. Biochim Biophys Acta. July 21, 1989;992(1):59-65.

1995

Buschmann MD, Grodzinsky AJ. A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng. May 1995;117(2):179-192.