Flow velocity-driven differentiation of human mesenchymal stromal cells in silk fibroin scaffolds: A combined experimental and computational approach

Autor: Vetsch, Jolanda R., Betts, Duncan C., Müller, Ralph, Hofmann, Sandra
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Bone Regeneration
Physiology
Cell Culture Techniques
lcsh:Medicine
Diagnostic Radiology
Bioreactors
Osteogenesis
Medicine and Health Sciences
Biomechanics
lcsh:Science
Tomography
Tissue Scaffolds
Animal Behavior
Radiology and Imaging
Physics
Bone and Joint Mechanics
Classical Mechanics
Cell Differentiation
Biomechanical Phenomena
Extracellular Matrix
Physical Sciences
Intercellular Signaling Peptides and Proteins
Imitation
Cellular Structures and Organelles
Rheology
Research Article
Cell Physiology
Imaging Techniques
Primary Cell Culture
Neuroimaging
Fluid Mechanics
Research and Analysis Methods
Time-Lapse Imaging
Continuum Mechanics
Bone and Bones
Calcification
Physiologic
Diagnostic Medicine
Tissue Repair
Humans
Fluid Flow
Cell Proliferation
Behavior
Tissue Engineering
lcsh:R
Biology and Life Sciences
Mesenchymal Stem Cells
Fluid Dynamics
X-Ray Microtomography
Cell Biology
Computed Axial Tomography
Cell Metabolism
lcsh:Q
Stress
Mechanical
Fibroins
Physiological Processes
Zoology
Developmental Biology
Neuroscience
Zdroj: PLoS ONE, 12 (7)
PLoS ONE, Vol 12, Iss 7, p e0180781 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: Mechanical loading plays a major role in bone remodeling and fracture healing. Mimicking the concept of mechanical loading of bone has been widely studied in bone tissue engineering by perfusion cultures. Nevertheless, there is still debate regarding the in-vitro mechanical stimulation regime. This study aims at investigating the effect of two different flow rates (vlow = 0.001m/s and vhigh = 0.061m/s) on the growth of mineralized tissue produced by human mesenchymal stromal cells cultured on 3-D silk fibroin scaffolds. The flow rates applied were chosen to mimic the mechanical environment during early fracture healing or during bone remodeling, respectively. Scaffolds cultured under static conditions served as a control. Time-lapsed micro-computed tomography showed that mineralized extracellular matrix formation was completely inhibited at vlow compared to vhigh and the static group. Biochemical assays and histology confirmed these results and showed enhanced osteogenic differentiation at vhigh whereas the amount of DNA was increased at vlow. The biological response at vlow might correspond to the early stage of fracture healing, where cell proliferation and matrix production is prominent. Visual mapping of shear stresses, simulated by computational fluid dynamics, to 3-D micro-computed tomography data revealed that shear stresses up to 0.39mPa induced a higher DNA amount and shear stresses between 0.55mPa and 24mPa induced osteogenic differentiation. This study demonstrates the feasibility to drive cell behavior of human mesenchymal stromal cells by the flow velocity applied in agreement with mechanical loading mimicking early fracture healing (vlow) or bone remodeling (vhigh). These results can be used in the future to tightly control the behavior of human mesenchymal stromal cells towards proliferation or differentiation. Additionally, the combination of experiment and simulation presented is a strong tool to link biological responses to mechanical stimulation and can be applied to various in-vitro cultures to improve the understanding of the cause-effect relationship of mechanical loading.
PLoS ONE, 12 (7)
ISSN:1932-6203
Databáze: OpenAIRE
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