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  4. Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal StemCell-Extracellular Matrix Interactions
 
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2021
Journal Article
Titel

Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal StemCell-Extracellular Matrix Interactions

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.
Author(s)
Pereira, Ana Rita
IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, 97070 Wuerzburg, Germany; Bernhard-Heine-Centrum for Locomotion Research, University of Wuerzburg, Wuerzburg, Germany
Lipphaus, Andreas
Biomechanics Research Group, Ruhr-University Bochum, Bochum, Germany
Ergin, Mert
Department of Biomaterials, Center of Energy Technology und Materials Science (TAO), University of Bayreuth, Bayreuth, Germany; IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, 97070 Wuerzburg
Salehi, Sahar
Department of Biomaterials, Center of Energy Technology und Materials Science (TAO), University of Bayreuth, Bayreuth, Germany
Gehweiler, Dominic
AO Research Institute Davos, Davos, Switzerland
Rudert, Maximilian
Department of Orthopedic Surgery, Koenig-Ludwig-Haus, University of Wuerzburg, Wuerzburg, Germany
Hansmann, Jan
Fraunhofer-Institut für Silicatforschung ISC
Herrmann, Marietta
IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, Wuerzburg, Germany; Bernhard-Heine-Centrum for Locomotion Research, University of Wuerzburg, 97074 Wuerzburg, Germany
Zeitschrift
Materials
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DOI
10.3390/ma14164431
Externer Link
Externer Link
Language
English
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Fraunhofer-Institut für Silicatforschung ISC
Tags
  • bone tissue engineering

  • Cell-matrix interaction

  • Compressive load

  • Fluid simulation

  • Human trabecular bone decellularization

  • In vitro modeling

  • Mechanotransduction

  • Shear stress

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