Aligned Nanofiber Topography Directs the Tenogenic Differentiation of Mesenchymal Stem Cells

Abstract

Abstract:Tendon is commonly injured, heals slowly and poorly, and often suffers re-injury after healing. This is due to failure of tenocytes to effectively remodel tendon after injury to recapitulate normal architecture, resulting in poor mechanical properties. One strategy for improving the outcome is to use nanofiber scaffolds and mesenchymal stem cells (MSCs) to regenerate tendon. Various scaffold parameters are known to influence tenogenesis. We designed suspended and aligned nanofiber scaffolds with the hypothesis that this would promote tenogenesis when seeded with MSCs. Our aligned nanofibers were manufactured using the previously reported non-electrospinning Spinneret-based Tunable Engineered Parameters (STEP) technique. We compared parallel versus perpendicular nanofiber scaffolds with traditional flat monolayers and used cellular morphology, tendon marker gene expression, and collagen and glycosaminoglycan deposition as determinants for tendon differentiation. We report that compared with traditional control monolayers, MSCs grown on nanofibers were morphologically elongated with higher gene expression of tendon marker scleraxis and collagen type I, along with increased production of extracellular matrix components collagen (p = 0.0293) and glycosaminoglycan (p = 0.0038). Further study of MSCs in different topographical environments is needed to elucidate the complex molecular mechanisms involved in stem cell differentiation.

Effects of substrate stiffness on the tenoinduction of human mesenchymal stem cells

“…Our group and other groups have reported on tenogenic effect of substrate driven cytoskeletal alignment on MSCs previously 5, 11–16, 21, 68, 69 . Collagen molecules are packed densely when they are registered in parallel (i.e.…”

3D Mimicry of Native‐Tissue‐Fiber Architecture Guides Tendon‐Derived Cells and Adipose Stem Cells into Artificial Tendon Constructs

“…Overall, these results demonstrate that, by closely recapitulating the architecture of native tendon niches, the 3D topography of the Woven scaffold can promote similar organization of hTDCs and hASCs on the constructs, leading to highly elongated and aligned cell morphologies induced by contact guidance mechanisms, even after prolonged periods of in vitro maturation. Considering the increasing number of studies reporting on the tenogenic commitment of stem cells based on the cascade of cellular events triggered by the anisotropic fibrous alignment of scaffold substrates, it is reasonable to expect that the microstructure of the Woven scaffolds will likely guide seeded hTDCs and hASCs into a tenogenic‐like phenotype (either maintaining or differentiating, respectively).…”

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

“…How biomaterial substrate mechanics and biochemistry interact to guide cell behavior has emerged as an important research topic with broad implications to biomaterial design [15][16][17]. Specifically for tendon repair, an aligned micro-or nanofiber structure is now understood to be a highly instructive biophysical cue that can direct tendon https://doi.org/10.1016/j.biomaterials.2020.120034 Received 30 March 2019; Received in revised form 4 April 2020; Accepted 5 April 2020 specific lineage differentiation [18][19][20][21][22][23][24][25]. Our own work has shown that deviations from aligned biomaterial surface structures may play a potentially important role in predisposing inflammatory response of attached tendon fibroblasts [26].…”