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@PHDTHESIS{Zhang:969118,
      author       = {Zhang, Xing},
      othercontributors = {Eschweiler, Jörg and Bleilevens, Christian},
      title        = {{O}steoblast derived extracellular vesicles induced by
                      dexamethasone: a novel biomimetic tool for enhancing
                      osteogenesis in vitro},
      school       = {Rheinisch-Westfälische Technische Hochschule Aachen},
      type         = {Dissertation},
      address      = {Aachen},
      publisher    = {RWTH Aachen University},
      reportid     = {RWTH-2023-08953},
      pages        = {1 Online-Ressource : Illustrationen, Diagramme},
      year         = {2023},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University; Dissertation, Rheinisch-Westfälische Technische
                      Hochschule Aachen, 2023},
      abstract     = {Extracellular vesicles (EVs) are newly appreciated
                      communicators involved in intercellular crosstalk, and have
                      emerged as a promising biomimetic tool for bone tissue
                      regeneration, overcoming many of the limitations associated
                      with cell-based therapies. However, the significance of
                      osteoblast-derived extracellular vesicles on osteogenesis
                      has not been fully established. In this present study, we
                      aim to investigate the therapeutic potential of
                      extracellular vesicles secreted from consecutive 14 days of
                      dexamethasone-stimulated osteoblasts (OB-EVDex) to act as a
                      biomimetic tool for regulating osteogenesis, and to
                      elucidate the underlying mechanisms. OB-EVDex treated groups
                      are compared to the clinically used osteo-inductor of BMP-2
                      as control. Our findings revealed that OB-EVDex have a
                      typical bilayer membrane nanostructure with an average
                      diameter of 178 ± 21 nm, and that fluorescently labeled
                      OB-EVDex were engulfed by osteoblasts in a time-dependent
                      manner. The proliferation, attachment, and viability
                      capacities of OB-EVDex-treated osteoblasts were
                      significantly improved when compared to untreated cells,
                      with the highest proliferative rate observed in the OB-EVDex
                      + BMP-2 group. Notably, combinations of OB-EVDex and BMP-2
                      markedly promoted osteogenic differentiation by positively
                      upregulating osteogenesis-related gene expression levels of
                      RUNX2, BGLAP, SPP1, SPARC, Col 1A1, and ALPL relative to
                      BMP-2 or OB-EVDex treatment alone. Mineralization assays
                      also showed greater pro-osteogenic potency after combined
                      applications of OB-EVDex and BMP-2, as evidenced by a
                      notable increase in mineralized nodules (calcium deposition)
                      revealed by Alkaline Phosphatase (ALP), Alizarin Red (ARS),
                      and von Kossa staining. Therefore, our findings shed light
                      on the potential of OB-EVDex as a new therapeutic option for
                      enhancing osteogenesis.},
      cin          = {533500-3 ; 931510},
      ddc          = {610},
      cid          = {$I:(DE-82)533500-3_20140620$},
      pnm          = {DFG project 429837092 - Differenzierte Chirurgische und
                      Immunologische Kontrolle nach Polytrauma im Langzeit
                      Großtiermodell (429837092)},
      pid          = {G:(GEPRIS)429837092},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2023-08953},
      url          = {https://publications.rwth-aachen.de/record/969118},
}