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Title: Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds

Abstract

Orthopaedic injuries, particularly those involving ligaments and tendons, are some of the most commonly treated ailments in the United States and are associated with both high costs and poor outcomes. Regenerative medicine strategies for tendon injuries could be enhanced by three-dimensional biomaterials that can promote cell alignment and pro-tenogenic differentiation of patientderived MSCs. We have previously described a collagenglycosaminoglycan (CG) scaffold possessing aligned structural features able to promote bone marrow MSC differentiation towards a tenogenic lineage, in the absence of growth factor supplementation. We aimed to employ a bioreactor to enhance MSC tenogenic differentiation within the aligned CG scaffold via cyclic tensile strain (CTS), and further to evaluate the relative effects of strain cycle duration and extended application of repeated cycles of CTS on MSC response. Human MSCs were cultured in CG scaffolds for up to 6 d under static (unloaded) or cyclic tensile strain (1 Hz) for 10 min every 6 h. Time-dependent activation of ERK 1/2 and p38 mechanotransduction pathways was observed within each 6 h strain cycle. MSCs remained viable throughout the experiment and application of CTS robustly upregulated the expression of tendon-specific extracellular matrix proteins and phenotypic markers. Simultaneously, CTS promoted increased phosphorylation of Smad 2/3,more » suggesting a link between tensile stimulation and TGF-β family growth factor production. Together, we demonstrated the design, fabrication and validation of a high-throughput tensile stimulation bioreactor to increase MSC tenogenic differentiation in porous CG scaffolds.« less

Authors:
 [1];  [2];  [3]
  1. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemical and Biomolecular Engineering
  2. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Bioengineering
  3. Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology, and Dept. of Chemical and Biomolecular Engineering
Publication Date:
Research Org.:
Univ. of Illinois, Urbana-Champaign, IL (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1423810
Grant/Contract Number:
FG02-07ER46453; FG02-07ER46471
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
eCells & Materials
Additional Journal Information:
Journal Volume: 33; Journal Issue: 2017; Journal ID: ISSN 1473-2262
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; collagen scaffold; mechanotransduction; bioreactor; cyclic tensile strain; mesenchymal stem cell; tendon

Citation Formats

Grier, W. K., Moy, A. S., and Harley, B. A.C. Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds. United States: N. p., 2017. Web. doi:10.22203/eCM.v033a17.
Grier, W. K., Moy, A. S., & Harley, B. A.C. Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds. United States. doi:10.22203/eCM.v033a17.
Grier, W. K., Moy, A. S., and Harley, B. A.C. Mon . "Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds". United States. doi:10.22203/eCM.v033a17. https://www.osti.gov/servlets/purl/1423810.
@article{osti_1423810,
title = {Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds},
author = {Grier, W. K. and Moy, A. S. and Harley, B. A.C.},
abstractNote = {Orthopaedic injuries, particularly those involving ligaments and tendons, are some of the most commonly treated ailments in the United States and are associated with both high costs and poor outcomes. Regenerative medicine strategies for tendon injuries could be enhanced by three-dimensional biomaterials that can promote cell alignment and pro-tenogenic differentiation of patientderived MSCs. We have previously described a collagenglycosaminoglycan (CG) scaffold possessing aligned structural features able to promote bone marrow MSC differentiation towards a tenogenic lineage, in the absence of growth factor supplementation. We aimed to employ a bioreactor to enhance MSC tenogenic differentiation within the aligned CG scaffold via cyclic tensile strain (CTS), and further to evaluate the relative effects of strain cycle duration and extended application of repeated cycles of CTS on MSC response. Human MSCs were cultured in CG scaffolds for up to 6 d under static (unloaded) or cyclic tensile strain (1 Hz) for 10 min every 6 h. Time-dependent activation of ERK 1/2 and p38 mechanotransduction pathways was observed within each 6 h strain cycle. MSCs remained viable throughout the experiment and application of CTS robustly upregulated the expression of tendon-specific extracellular matrix proteins and phenotypic markers. Simultaneously, CTS promoted increased phosphorylation of Smad 2/3, suggesting a link between tensile stimulation and TGF-β family growth factor production. Together, we demonstrated the design, fabrication and validation of a high-throughput tensile stimulation bioreactor to increase MSC tenogenic differentiation in porous CG scaffolds.},
doi = {10.22203/eCM.v033a17},
journal = {eCells & Materials},
number = 2017,
volume = 33,
place = {United States},
year = {Mon Mar 20 00:00:00 EDT 2017},
month = {Mon Mar 20 00:00:00 EDT 2017}
}

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