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Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation

Ramani-Mohan, R. -K (författare)
Schwedhelm, I. (författare)
Wistrand, Anna Finne, 1976- (författare)
KTH,Fiber- och polymerteknologi
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Krug, M. (författare)
Schwarz, T. (författare)
Jakob, F. (författare)
Walles, H. (författare)
Hansmann, J. (författare)
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 (creator_code:org_t)
2017-11-10
2018
Engelska.
Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley and Sons Ltd. - 1932-6254 .- 1932-7005. ; 12:3, s. e1474-e1479
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation. 

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Nyckelord

bioreactor
computational fluid dynamics
mechanical strain
mechanosensitive reporter gene constructs
mesenchymal stem cells
osteogenesis
3 (4
5 dimethyl 2 thiazolyl) 2
5 diphenyltetrazolium bromide
alizarin red s
alkaline phosphatase
bone morphogenetic protein 2
collagen type 1
osteocalcin
osteonectin
osteopontin
transcription factor AP 1
transcription factor RUNX2
Article
bone deformation
bone development
bone mineralization
bone regeneration
bone remodeling
bone stress
cell culture
cell differentiation
cell lineage
cell maturation
controlled study
enzyme activity
gene expression
human
human cell
luciferase assay
mathematical model
mesenchymal stem cell
osteoblast
porosity
priority journal
quantitative analysis
shear stress
stem cell
stress
three dimensional imaging

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