Many problems concerning skeletal and connective tissue repair, and orthopaedic im plant design and fixation, relate to the responses of skeletal and connective tissues to mechanical loading. To improve treatm ent of orthopaedic injury, and to prevent or reverse some processes of connective tissue degeneration, one m ust understand the mechanical factors involved in skeletal and connective tissue differentiation, maintenance, and modulation.

Drawing on the previously described 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 intermittently imposed hydrostatic stress and distortional (octahedral shear) strain are critical mechanical param eters involved in creating and m aintaining a tissue phenotype such as fibrous tissue, cartilage, fibrocartilage, and bone. Loads which create negative hydrostatic stress in a differentiating tissue stimulate the net production of cartilaginous matrix constituents. Loads which cause significant distortional strain in a differentiating tissue stimulate the net production of fibrous matrix constituents. 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 w rapping 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.

In a finite element analysis of the cement-bone interface supporting a unicondylar tibial component, I have found that fibrocartilage forms in differentiating tissue exposed to interm ittent distortional strain of at least 10 percent and intermit tent compressive hydrostatic stress of at least 0.7 MPa. Fibrous tissue forms at the cement-bone interface where intermittent distortional strain is at least 10 percent and compressive hydrostatic stress is less than approximately 0.7 MPa.

Finally, I have conducted an in vivo study designed to mechanically m anipulate healing and regenerating 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. In addition, these studies revealed general ranges of interm ittent hydrostatic stress and distortional strain which influence tissue differentiation and modulation. H ydrostatic stress and distortional strain, param eters that are intimately related to cell pressure and cell shape changes respectively, appear to be tissue level mechanical param eters that control skeletal and connective tissue responses to mechanical stimulation.