Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell−Extracellular Matrix Interactions

Please always quote using this URN: urn:nbn:de:bvb:20-opus-245012
  • 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 forIn 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.show moreshow less

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Metadaten
Author: Ana Rita Pereira, Andreas Lipphaus, Mert Ergin, Sahar Salehi, Dominic Gehweiler, Maximilian Rudert, Jan Hansmann, Marietta Herrmann
URN:urn:nbn:de:bvb:20-opus-245012
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Orthopädie
Language:English
Parent Title (English):Materials
ISSN:1996-1944
Year of Completion:2021
Volume:14
Issue:16
Article Number:4431
Source:Materials 2021, 14(16), 4431; https://doi.org/10.3390/ma14164431
DOI:https://doi.org/10.3390/ma14164431
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:bone tissue engineering; cell-matrix interaction; compressive load; fluid simulation; human trabecular bone decellularization; in vitro modeling; mechanotransduction; shear stress
Release Date:2022/01/10
Date of first Publication:2021/08/07
Open-Access-Publikationsfonds / Förderzeitraum 2021
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International