Mihaela Roxana Cimpan

To improve the wear resistance of articulating metallic joint endoprostheses, the surfaces can be coated with titanium niobium nitride (TiNbN). Under poor tribological conditions or malalignment, wear can occur on these implant surfaces in situ. This study investigated the biological response of human osteoblasts to wear particles generated from TiNbN‐coated hip implants. Abrasive particles were generated in a hip simulator according to ISO 14242‐1/−2 and extracted with Proteinase K. Particle characteristics were evaluated by electron microscopy and energy dispersive x‐ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP‐MS) and dynamic light scattering (DLS) measurements. Human osteoblasts were exposed to different particle dilutions (1:20, 1:50, and 1:100), and cell viability and gene expression levels of osteogenic markers and inflammatory mediators were analyzed after 4 and 7 days. Using ICP‐MS, EDS, and DLS measurements, ~70% of the particles were identified as TiNbN, ranging from 39 to 94 nm. The particles exhibited a flat and subangular morphology. Exposure to particles did not influence cell viability and osteoblastic differentiation capacity. Protein levels of collagen type 1, osteoprotegerin, and receptor activator of nuclear factor κB ligand were almost unaffected. Moreover, the pro‐inflammatory response via interleukins 6 and 8 was minor induced after particle contact. A high number of TiNbN wear particles only slightly affected osteoblasts' differentiation ability and inflammatory response compared to metallic particles. Nevertheless, further studies should investigate the role of these particles in peri‐implant bone tissue, especially concerning other cell types.

We aimed to investigate whether molecular clues from the extracellular matrix (ECM) can induce oral epithelial differentiation of pluripotent stem cells. Mouse embryonic stem cells (ESC) of the feeder-independent cell line E14 were used as a model for pluripotent stem cells. They were first grown in 2D on various matrices in media containing vitamin C and without leukemia inhibitory factor (LIF). Matrices investigated were gelatin, laminin, and extracellular matrices (ECM) synthesized by primary normal oral fibroblasts and keratinocytes in culture. Differentiation into epithelial lineages was assessed by light microscopy, immunocytochemistry, and flow cytometry for cytokeratins and stem cell markers. ESC grown in 2D on various matrices were afterwards grown in 3D organotypic cultures with or without oral fibroblasts in the collagen matrix and examined histologically and by immunohistochemistry for epithelial (keratin pairs 1/10 and 4/13 to distinguish epidermal from oral epithelia and keratins 8,18,19 to phenotype simple epithelia) and mesenchymal (vimentin) phenotypes. ECM synthesized by either oral fibroblasts or keratinocytes was able to induce, in 2D cultures, the expression of cytokeratins of the stratified epithelial phenotype. When grown in 3D, all ESC developed into two morphologically distinct cell populations on collagen gels: (i) epithelial-like cells organized in islands with occasional cyst- or duct-like structures and (ii) spindle-shaped cells suggestive of mesenchymal differentiation. The 3D culture on oral fibroblast-populated collagen matrices was necessary for further differentiation into oral epithelia. Only ESC initially grown on 2D keratinocyte or fibroblast-synthesized matrices reached full epithelial maturation. In conclusion, ESC can generate oral epithelia under matrix instruction.