Mechanobiology of multipotent mesenchymal tissue differentiation

Mesenchymal tissue is a multipotent tissue that is able to differentiate into a variety of skeletal tissues including bone, cartilage, fibrocartilage, or fibrous tissue. Mechanical stresses play an important role in regulating tissue differentiation during skeletal regeneration. This dissertation presents four studies addressing this significant issue.; The first study examines the role of mechanical loading during oblique pseudarthrosis formation. It implements a previously developed mechanobiological tissue differentiation concept relating hydrostatic stress and tensile strain to skeletal tissue regeneration. Using two-dimensional finite element (FE) analysis, locations of cartilage, fibrocartilage, and bone are predicted during initial pseudarthrosis development. Further conclusions are that excessive tensile strains cause mesenchymal tissue failure and excessive hydrostatic pressures cause periosteal bone resorption.; The second study is an experimental analysis of tissue differentiation during mandibular distraction osteogenesis (DO). Harvested rat mandibles are mechanically tested at four different time points during a DO protocol. Results from these mechanical tests are used to calculate distraction-induced forces, stresses, and strains in the tissue regenerate. It is found that tensile strains from 9.9–12.5%/distraction induce the highest rate of bone regeneration.; The third study utilizes three-dimensional FE analysis to determine local hydrostatic stresses and tensile strains within the tissue regenerate. Computed tomography image data (specimens from second study) are used to create true geometry FE models of the tissue regenerate. Hydrostatic stresses and tensile strains resulting from a simulated distraction are correlated to skeletal tissue regeneration throughout mandibular DO.; The final study examines material property changes during soft skeletal tissue regeneration. Using a fiber-reinforced poroelastic model, time-dependent adaptations in tensile elastic modulus, permeability, and compressive aggregate modulus during articular cartilage, fibrocartilage, or fibrous tissue formation are determined. In this mathematical approach, intermittently imposed fluid pressure and tensile strain regulate proteoglycan and collagen synthesis. Implementing a computer algorithm based on this concept, material property adaptations during soft skeletal tissue differentiation are simulated.; The results of this dissertation verify the importance of mechanobiological factors in multipotent mesenchymal tissue differentiation. The relationships examined are essential to understanding the time-dependent changes that occur during differentiation as a result of mechanical loads at sites of regenerating tissue.