@article{HochleitnerJuengstBrownetal.2015,
  author    = {Hochleitner, Gernot and J{\"u}ngst, Tomasz and Brown, Toby D and Hahn, Kathrin and Moseke, Claus and Jakob, Franz and Dalton, Paul D and Groll, J{\"u}rgen},
  title     = {Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing},
  series = {Biofabrication},
  volume    = {7},
  journal   = {Biofabrication},
  number    = {3},
  doi       = {10.1088/1758-5090/7/3/035002},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254053},
  year      = {2015},
  abstract  = {The aim of this study was to explore the lower resolution limits of an electrohydrodynamic process combined with direct writing technology of polymer melts. Termed melt electrospinning writing, filaments are deposited layer-by-layer to produce discrete three-dimensional scaffolds for in vitro research. Through optimization of the parameters (flow rate, spinneret diameter, voltage, collector distance) for poly-ϵ-caprolactone, we could direct-write coherent scaffolds with ultrafine filaments, the smallest being 817 ± 165 nm. These low diameter filaments were deposited to form box-structures with a periodicity of 100.6 ± 5.1 μm and a height of 80 μm (50 stacked filaments; 100 overlap at intersections). We also observed oriented crystalline regions within such ultrafine filaments after annealing at 55 °C. The scaffolds were printed upon NCO-sP(EO-stat-PO)-coated glass slide surfaces and withstood frequent liquid exchanges with negligible scaffold detachment for at least 10 days in vitro.},
  language  = {en}
}
@article{EbertBenischKrugetal.2015,
  author    = {Ebert, Regina and Benisch, Peggy and Krug, Melanie and Zeck, Sabine and Meißner-Weigl, Jutta and Steinert, Andre and Rauner, Martina and Hofbauer, Lorenz and Jakob, Franz},
  title     = {Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells},
  series = {Stem Cell Research},
  volume    = {15},
  journal   = {Stem Cell Research},
  doi       = {10.1016/j.scr.2015.06.008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148491},
  pages     = {231-239},
  year      = {2015},
  abstract  = {The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.},
  language  = {en}
}
@article{WehrleLiedertHeilmannetal.2015,
  author    = {Wehrle, Esther and Liedert, Astrid and Heilmann, Aline and Wehner, Tim and Bindl, Ronny and Fischer, Lena and Haffner-Luntzer, Melanie and Jakob, Franz and Schinke, Thorsten and Amling, Michael and Ignatius, Anita},
  title     = {The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice},
  series = {Disease Models \& Mechanisms},
  volume    = {8},
  journal   = {Disease Models \& Mechanisms},
  doi       = {10.1242/dmm.018622},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144700},
  pages     = {93-104},
  year      = {2015},
  abstract  = {Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (mu CT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81\%) and bone formation (-80\%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+ 1398\%) and bone formation (+637\%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ER alpha in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERa might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.},
  language  = {en}
}
@article{WehrleLiedertHeilmannetal.2015,
  author    = {Wehrle, Esther and Liedert, Astrid and Heilmann, Aline and Wehner, Tim and Bindl, Ronny and Fischer, Lena and Haffner-Luntzer, Melanie and Jakob, Franz and Schinke, Thorsten and Amling, Michael and Ignatius, Anita},
  title     = {The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice},
  series = {Disease Models \& Mechanisms},
  volume    = {8},
  journal   = {Disease Models \& Mechanisms},
  doi       = {10.1242/dmm.018622},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121109},
  pages     = {93-104},
  year      = {2015},
  abstract  = {Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81\%) and bone formation (-80\%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398\%) and bone formation (+637\%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.},
  language  = {en}
}
@article{SteinertKunzPrageretal.2015,
  author    = {Steinert, Andre F. and Kunz, Manuela and Prager, Patrick and G{\"o}bel, Sascha and Klein-Hitpass, Ludger and Ebert, Regina and N{\"o}th, Ulrich and Jakob, Franz and Gohlke, Frank},
  title     = {Characterization of bursa subacromialis-derived mesenchymal stem cells},
  series = {Stem Cell Research \& Therapy},
  volume    = {6},
  journal   = {Stem Cell Research \& Therapy},
  number    = {114},
  doi       = {10.1186/s13287-015-0104-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126446},
  year      = {2015},
  abstract  = {Introduction The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level. Methods BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip. BS cells and BMSCs were compared upon their potential to proliferate and differentiate along chondrogenic, osteogenic and adipogenic lineages under specific culture conditions. Expression profiles of markers associated with mesenchymal phenotypes were comparatively evaluated by flow cytometry, immunohistochemistry, and whole genome array analyses. Results BS cells and BMSCs appeared mainly fibroblastic and revealed almost similar surface antigen expression profiles, which was \(CD44^+, CD73^+, CD90^+, CD105^+, CD106^+\),\(STRO-1^+, CD14^-, CD31^-, CD34^- , CD45^-, CD144^-\). Array analyses revealed 1969 genes upregulated and 1184 genes downregulated in BS cells vs. BMSCs, indicating a high level of transcriptome similarity. After 3 weeks of differentiation culture, BS cells and BMSCs showed a similar strong chondrogenic, adipogenic and osteogenic potential, as shown by histological, immunohistochemical and RT-PCR analyses in contrast to the respective negative controls. Conclusions Our in vitro characterizations show that BS cells fulfill all characteristics of mesenchymal stem cells, and therefore merit further attention for the development of improved therapies for various shoulder pathologies.},
  language  = {en}
}