eCM (Eur Cell Mater / e Cells & Materials) eCM Open Access Scientific Journal
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2017   Volume No 33 – pages 227-239

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

Authors: WK Grier, AS Moy, BAC Harley

Address: Department of Chemical and Biomolecular Engineering, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 110 Roger Adams Laboratory, 600 S. Mathews Ave, Urbana, IL 61801, USA

E-mail: bharley at

Key Words: collagen scaffold, mechanotransduction, bioreactor, cyclic tensile strain, mesenchymal stem cell, tendon.


Publication date: March 20th 2017

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 patient-derived MSCs. We have previously described a collagen-glycosaminoglycan (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.

Article download: Pages 227-239 (PDF file)