| To improve treatment of orthopaedic injury and disease, one should understand how mechanical stimuli influence skeletal and connective tissue differentiation, maintenance, and modulation. Drawing on the mechanically-based tissue differentiation concepts of Pauwels, Perren et al., and Carter et al., and on recent in vitro studies on the metabolic effects of mechanical stimulation in cultured cells and tissues, I hypothesize that intermittent negative hydrostatic stress in a differentiating tissue stimulates the net production of cartilaginous matrix constituents. In addition, I hypothesize that intermittent distortional strain in a differentiating tissue stimulates the net production of fibrous matrix constituents and that bone tissue may form in regions of low stresses and strains.;I have conducted four studies to test this hypothesis. Using finite element analyses to examine a tendon wrapping around a bone, I have found that fibrocartilage is formed when the matrix of the composite tendon tissue is exposed to at least 2 to 5 MPa of compressive hydrostatic stress. To confirm this analytical result, I have pressurized pieces of tendon in vitro and found that hydrostatic pressure of 6 MPa applied for eight hours results in increased sulfate incorporation into glycosaminoglycans.;Using finite element analysis to model the cement-bone interface supporting a unicondylar tibial component, I have found that fibrocartilage forms in differentiating tissue exposed to intermittent distortional strain greater than 10 percent and intermittent compressive hydrostatic stress greater than 0.7 MPa. Fibrous tissue forms at the cement-bone interface where intermittent distortional strain is greater than 10 percent and compressive hydrostatic stress is less than 0.7 MPa.;Finally, I have conducted an in vivo study designed to mechanically manipulate differentiating tissue. I found that fibrous tissue formed in regions of differentiating tissue subjected to distortional strain greater than approximately 10 percent. Cartilage and bone formed in areas of lower distortional strain.;The results of these studies supported the tissue differentiation hypothesis. Hydrostatic stress and distortional strain, parameters that are intimately related to cell pressure and cell shape respectively, appear to be tissue level mechanical parameters that control skeletal and connective tissue responses to mechanical stimulation. |
