@article{RamirezRodriguezPereiraHerrmannetal.2021,
  author    = {Ram{\´i}rez-Rodr{\´i}guez, Gloria Bel{\´e}n and Pereira, Ana Rita and Herrmann, Marietta and Hansmann, Jan and Delgado-L{\´o}pez, Jos{\´e} Manuel and Sprio, Simone and Tampieri, Anna and Sandri, Monica},
  title     = {Biomimetic mineralization promotes viability and differentiation of human mesenchymal stem cells in a perfusion bioreactor},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {3},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22031447},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285804},
  year      = {2021},
  abstract  = {In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.},
  language  = {en}
}
@article{PereiraTrivanovićStahlhutetal.2022,
  author    = {Pereira, Ana Rita and Trivanović, Drenka and Stahlhut, Philipp and Rudert, Maximilian and Groll, J{\"u}rgen and Herrmann, Marietta},
  title     = {Preservation of the na{\"i}ve features of mesenchymal stromal cells in vitro: Comparison of cell- and bone-derived decellularized extracellular matrix},
  series = {Journal of Tissue Engineering},
  volume    = {13},
  journal   = {Journal of Tissue Engineering},
  doi       = {10.1177/20417314221074453},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268835},
  pages     = {1-12},
  year      = {2022},
  abstract  = {The fate and behavior of bone marrow mesenchymal stem/stromal cells (BM-MSC) is bidirectionally influenced by their microenvironment, the stem cell niche, where a magnitude of biochemical and physical cues communicate in an extremely orchestrated way. It is known that simplified 2D in vitro systems for BM-MSC culture do not represent their na{\"i}ve physiological environment. Here, we developed four different 2D cell-based decellularized matrices (dECM) and a 3D decellularized human trabecular-bone scaffold (dBone) to evaluate BM-MSC behavior. The obtained cell-derived matrices provided a reliable tool for cell shape-based analyses of typical features associated with osteogenic differentiation at high-throughput level. On the other hand, exploratory proteomics analysis identified native bone-specific proteins selectively expressed in dBone but not in dECM models. Together with its architectural complexity, the physico-chemical properties of dBone triggered the upregulation of stemness associated genes and niche-related protein expression, proving in vitro conservation of the na{\"i}ve features of BM-MSC.},
  language  = {en}
}
@article{PereiraLipphausErginetal.2021,
  author    = {Pereira, Ana Rita and Lipphaus, Andreas and Ergin, Mert and Salehi, Sahar and Gehweiler, Dominic and Rudert, Maximilian and Hansmann, Jan and Herrmann, Marietta},
  title     = {Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {16},
  issn      = {1996-1944},
  doi       = {10.3390/ma14164431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245012},
  year      = {2021},
  abstract  = {In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10\% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.},
  language  = {en}
}