(717c) Impact of Mechanical Pre-Stretch On Axonal Growth and Myelination

Spinal cord injury (SCI) is a disease of the central nervous system. Current therapeutic approaches focus on axonal regeneration, remyelination, and inhibition of inflammatory responses. Much of the research has focused on axonal regeneration, which has met with some success. However, remyelination has not been as extensively studied and remains a challenge in SCI. Remyelination is critical for successful functioniong of regenerated nerves. In this study, we discuss how an anisotropic surface arising from mechanical pre-stretch affects axonal regeneration and myelination..

Initiation of myelination has been shown to depend highly on the thickness of the axon. Using engineered nanofibers, it was found that above a certain fiber thickness, myelination initiates on the fibers independent of axonal signaling [1]. Concomitantly dorsal root ganglion (DRG) cells seeded on a stretch-growth system aligned in the stretched direction [2]. These DRG cells formed longer and thicker axons as the stretch on the surface increased. Their results showed some degree of myelination. We previously demonstrated that mesenchymal stem cells aligned on pre-stretch induced anisotropic surface, because the cells can sense a larger effective stiffness in the stretched direction than in the perpendicular direction. We explore how axons on a pre-stretched surface are impacted by the degree of pre-stretch (10%, 20%, or 30% pre-stretch) on the orientation, thickness and length of the axons as well as myelination.

[1] S. Lee, M.K. Leach, S.A. Redmond, S.Y.C. Chong, S.H. Mellon, S.J. Tuck, Z.Q. Feng, J.M. Corey, J.R. Chan, A culture system to study oligodendrocyte myelination processes using engineered nanofibers, Nature Methods 9 (2012) 917-+.

[2] B.J. Pfister, A. Iwata, A.G. Taylor, J.A. Wolf, D.F. Meaney, D.H. Smith, Development of transplantable nervous tissue constructs comprised of stretch-grown axons, Journal of Neuroscience Methods 153 (2006) 95-103.