title: Tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells dictated by properties of braided submicron fibrous scaffolds.
abstract: Tendon and ligament (T/L) engineering is a growing area of research with potential to address the inadequacies of current T/L defect treatments. Our group previously developed braided submicron fibrous scaffolds (BSMFSs) and demonstrated the viability of BSMFSs for T/L tissue engineering. The objective of this study was to investigate the effect of fiber chemistry and braiding angle on BSMFS mechanical properties and in turn, tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) seeded on BSMFSs subjected to cyclic tensile stimulation in the absence of tenogenic medium. By varying fiber chemistry and/or braiding angle, BSMFSs with a range of mechanical properties were produced. We found that fiber chemistry dictated cell adhesion while braiding angle dictated the tissue-specific lineage commitment of hiPSC-MSCs. Scaffolds braided with large angles better supported hiPSC-MSC tenogenic differentiation as evidenced by the production of T/L-associated markers, downregulation of osteogenic markers, and expression of fibroblast-like, spindle cell morphology compared to scaffolds braided with small angles. Our results demonstrate the importance of substrate properties and mechanical stimulation on tenogenic differentiation. These results also demonstrate the versatility of BSMFSs and the potential of hiPSC-MSCs for T/L tissue engineering.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Czaplewski
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Tsai
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Duenwald-Kuehl
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Vanderby
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: li@ortho.wisc.edu.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Li
mesh_terms: D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005355:Fibrosis; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008022:Ligaments; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D013710:Tendons / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Induced pluripotent stem cell; Ligament; Submicron fiber; Tendon; Tissue engineering