Effectiveness of magnetically aligned collagen for neural regeneration in vitro and in vivo

Abstract

We investigated the effectiveness of using magnetically aligned collagen (after exposure to a maximum 8-T magnetic field) for nerve regeneration in both an in vitro and in vivo model. Neurite outgrowth from embryonic chick dorsal root ganglion (DRG) neurons was significantly greater on magnetically aligned collagen gel than on control gel, and was dependent on magnetic field strength. Silicone tubes (15 mm length) filled with collagen gel formed bridges between severed rat sciatic nerves. We prepared tubes for four groups: collagen gel only (COL), magnetically aligned collagen gel (M-COL), collagen gel mixed with Schwann cells (S-COL), and magnetically aligned collagen gel mixed with Schwann cells (M-S-COL). The ratio of infiltrating regenerated nerves was higher in the M-COL group compared to the COL group at 8 weeks post-operation. There were no significant differences between the two groups with and without Schwann cells. Compound action potentials showed higher amplitude and shorter latency in the M-COL than COL group at 12 weeks post-operation. The number and diameter of regenerated axons increased significantly in the M-COL compared with the COL group at 12 weeks post-operation. Here we demonstrated that magnetically orientated collagen promoted nerve regeneration using both an in vitro and in vivo model.

Perspective: Ferromagnetic Liquids

“…Examples range from initiating cell differentiation or material degradation, to assembling components for tissue organization, aligning cell and matrix fibers [74]. The directed regeneration of aligned collagen fibers [75] and oriented neural cells requires only small magnetic fields [76], which can be provided by ferromagnetic liquid constructs. The latter could be remotely positioned around the growing cells or organ tissues, either in the form of flowable magnetic emulsion droplets or individual integrated liquid tubule (Figure 7a).…”

Templated Assembly of Collagen Fibers Directs Cell Growth in 2D and 3D

“…However, collagen casting techniques are incapable of modifying the microstructural alignment of collagen fibers within hydrogels. Various forms of physical manipulation including exposure to strain 26 , 27 , fluid shear 28 – 30 , and electromagnetic fields 29 , 31 , 32 have been explored to improve collagen fiber alignment within hydrogels, but these approaches are all potentially limited by the amount of material that can be processed at a given time and the requirement of relatively sophisticated instrumentation for controlling the fiber alignment, e.g., mechanical setups, flow cells, and powerful magnetic systems. Attempts have also been made to manipulate the microstructural alignment of collagen sponges by modifying the freeze-drying process to produce discontinuous ellipsoid pores, but the effect on collagen fiber alignment is minimal and trace amounts of porogens may remain in the final collagen biomaterial 33 – 35 .…”

Using Remote Fields for Complex Tissue Engineering

“…Strong magnetic fields have been widely used to orient matrix fibers during gelation, for example, Eguchi and coworkers recently used an 8 T field to fabricate aligned collagen hydrogels that could guide Schwann cell orientation [17] (Figure 2A). However, the recent trend has seen the introduction of magnetically susceptible components that allow alignment using much weaker magnetic fields.…”

“…Remote Fields in Tissue Engineering: Literature Examples and Inspiration Figure 1. (A) Magnets (shown in gray) offer a relatively simple and accessible method for manipulating the position of magnetized cells [28], aligning matrix fibers [17], or patterning growth factor gradients [22]. (B) Focused optical fields (shown in red) provide high spatial resolution that can be used for (Figure legend continued at the bottom of the next page.…”