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Neural crest stem cells (NCSCs) are embryonic multipotent cells that give rise to a wide range of cell types that include those forming the peripheral neural cells and the mesodermal cells of the face including the facial bones. In neonatal and adult skin, skin-derived precursor cells (SKPs) are multipotent dermal precursors that share similarities with NCSCs and can differentiate into peripheral neural and mesodermal cells, such as adipocytes. Based on the similarities between SKPs and NCSCs, I asked, in this thesis, whether rodent or human SKPs can differentiate into skeletal mesodermal cell types by determining their ability to differentiate into osteoblasts and chondrocytes. In culture, rodent and human SKPs differentiated into alkaline phosphatase-, osteopontin- and type-I collagen-positive osteoblasts that produced mineral deposits and into type-II collagen expressing chondrocytes. Clonal analysis showed that SKPs are multipotent for the osteogenic and chondrogenic lineages. To ask whether SKPs can generate these cells in vivo, genetically-tagged naïve rat SKPs were transplanted into a tibia bone fracture model. Six weeks post-transplantation, SKP-derived osteoblasts and osteocytes were present in the newly formed bone, showing their osteogenic differentiation in vivo. At three weeks post-transplantation, some of the injected cells differentiated into hypertrophic chondrocytes in the callus and others into perivascular cells in areas just outside the callus. To test whether it is the local environment that dictates the phenotype of transplanted SKPs, GFP-tagged undifferentiated rat SKPs were injected into the hypodermis of the skin, an adipogenic environment. Four weeks post-transplantation, SKPs differentiated into adipocytes, but not in inappropriate cell types. These results further the known differentiation potential of SKPs, show that local environment of a bone fracture or the hypodermis of the skin is sufficient to induce the differentiation of undifferentiated SKPs into appropriate cell types and suggest the use of SKPs as source of mesodermal precursor cells for cell therapy.

Neural crest stem cells (NCSCs) are embryonic multipotent cells that give rise to a wide range of cell types that include those forming the peripheral neural cells and the mesodermal cells of the face including the facial bones. In neonatal and adult skin, skin-derived precursor cells (SKPs) are multipotent dermal precursors that share similarities with NCSCs and can differentiate into peripheral neural and mesodermal cells, such as adipocytes. Based on the similarities between SKPs and NCSCs, I asked, in this thesis, whether rodent or human SKPs can differentiate into skeletal mesodermal cell types by determining their ability to differentiate into osteoblasts and chondrocytes. In culture, rodent and human SKPs differentiated into alkaline phosphatase-, osteopontin- and type-I collagen-positive osteoblasts that produced mineral deposits and into type-II collagen expressing chondrocytes. Clonal analysis showed that SKPs are multipotent for the osteogenic and chondrogenic lineages. To ask whether SKPs can generate these cells in vivo, genetically-tagged naïve rat SKPs were transplanted into a tibia bone fracture model. Six weeks post-transplantation, SKP-derived osteoblasts and osteocytes were present in the newly formed bone, showing their osteogenic differentiation in vivo. At three weeks post-transplantation, some of the injected cells differentiated into hypertrophic chondrocytes in the callus and others into perivascular cells in areas just outside the callus. To test whether it is the local environment that dictates the phenotype of transplanted SKPs, GFP-tagged undifferentiated rat SKPs were injected into the hypodermis of the skin, an adipogenic environment. Four weeks post-transplantation, SKPs differentiated into adipocytes, but not in inappropriate cell types. These results further the known differentiation potential of SKPs, show that local environment of a bone fracture or the hypodermis of the skin is sufficient to induce the differentiation of undifferentiated SKPs into appropriate cell types and suggest the use of SKPs as source of mesodermal precursor cells for cell therapy.

A multi-directional wear apparatus was developed to simulate the kinematic motion of diarthrodial joints. A comprehensive evaluation including biotribological and biomechanical characterization of articular surfaces was performed with concomitant translational and oscillating rotational motion similar to that experienced in vivo. Various system parameters were evaluated in the designed experiments including normal load magnitude (high/low), surface quality (defect/no defect), and wear pattern (with/without rotation). Biomechanical characterization was achieved through stress relaxation and dynamic cyclical testing. Quasi-linear viscoelastic theory was used to curve-fit the stress relaxation data, while the dynamic data was used to determine the dynamic properties through Fast Fourier Transform analysis and verify the assumptions posed with the QLV theory.Overall tissue compression was significantly dependent on load magnitude (pstatic was significantly dependent on surface quality (pinitial was significantly dependent on both surface quality (pComparisons of the curve-fit parameters showed a significant decrease in pre- vs post-wear elastic response, A, and viscous response, c. In addition, the short term relaxation response, τ1, showed a significant decrease between no defect (0.801 ± 0.13 sec) and a defect (0.679 ± 0.16 sec). lGlpost-wear/lGlpre-wear tan δ , was generally greater while lGl was less for those specimens experiencing rotation Qualitatively, SEM photographs revealed the mechanical degradation of the tissue surface due to wear. Surfaces with a defect had increased wear debris, which ultimately contributes to third body wear. Surfaces without a defect had preferentially aligned abrasions, while those surfaces outside the wear path showed no signs of wear.Significant correlation was detected between the μstatic and μinitial for both the nonliner viscous response, B (p2 (p<0.013 and p<0.062). Thus, the comprehensive evaluation of biomechanical and biotribological characteristics suggests the new wear regime and standardization of analysis techniques will aid in the development of functional articular repair and clinical repair techniques.