Biomedical Engineering Reference
In-Depth Information
injuries) resulting in a discontinuity of the cord. The majority of the clinical cases are the
result of a temporary compression of the cord that leaves the cord surface intact (closed
injuries 73%). Three types of compression injuries are described: massive compression,
contusion, and solid cord injury (E.Schmidt et al., 2003; Erschbamer, 2007).
CNS axons do not regenerate appreciably in their native environment. Several glycoproteins
in the native extracellular environment (myelin) of the CNS are inhibitory for regeneration.
Regeneration in the adult CNS requires a multi-step process. First, the injured neuron must
survive, and then the damaged axon must extend its cut processes to its original neuronal
targets. According to Horner and Gage investigation, once contact is made, the axon needs
to be re-myelinated and functional synapses need to form on the surface of the targeted
neurons (Horner and Gage., 2000).
In addition to the nerve graft and other natural tissues, such as autologous muscle and vein
grafts, biopolymers can be a practical tool to provide neurotrophic and/or cellular support
while simultaneously guiding axonal regeneration (Stokols et al., 2004; Rodriguez et al.,
2000). Indeed, numerous natural and synthetic polymers have been used as scaffolds or
within scaffolds for peripheral and central nerve regeneration.
Filling of the interior channels with appropriate cell facilitates axon regeneration. The Schwann
cell (SC) and its basal lamina are crucial components in the environment through which
regenerating axons grow to reach their peripheral targets. They produce myelin, which has
important effects on the speed of transmission of electrical signals and are shown to enhance
the regeneration of axons in both the peripheral and central nervous systems (Erschbamer,
2007; Alovskaya et al., 2007). Therefore, it seems that application of a nerve grafts (scaffolds)
coated with SCs can be an appropriate method for spinal cord regeneration.
Considering the requirements of scaffolds in general and in particular, i.e. in neural tissue
engineering, materials appropriate for SC seeding should posse some additional features. In
order to successfully design a scaffold that can be used as treatment for SCI, many
considerations must be taken into account. The scaffold should lessen glial scar formation,
while containing sites for cell adhesion to allow regenerating neurons to extend axons into
the injury site (Willerth et al., 2007; Radulescu et al., 2007).
Among natural materials, Matin in 2004 found that implants coated with collagen are more
successful than the bare ones. Stokolos et al. chose to fabricate scaffolds with agarose for
several reasons. First, when implanted into lesion cavities in the spinal cord as an
unstructured solid agarose hydrogel, it did not evoke an immune or inflammatory response
and was stable for at least 1 month. Second, it was observed that neither axons nor cells
penetrated solid agarose hydrogels, which suggested that walls composed of agarose could
effectively delineate pathways for regenerating axons. Third, freeze-drying could be used to
fabricate agarose into soft and flexible scaffold. Finally, neurotrophic factors, proven to elicit
robust axonal growth could be easily incorporated into these scaffolds.
In other researches, Alvskaya et al. described that by using fibronectin as a substrate in an
in
vivo
model of spinal cord repair, the growth of neuritis within the material is accompanied
by migration of SCs into the graft and the presence of reactive astrocytes at its surface
continued. Within the first 2 weeks of implantation, a number of cells and cellular elements
replaced the FN mat as it dissolved. The first cells to infiltrate FN mats were macrophages.
The presence of integrin receptors on Schwann cells may be responsible for the extensive
infiltration of Schwann cells. The close spatial correspondence between laminin tubules and
Schwann cells suggests that they were deposited by the Schwann cells (Alovskaya et al.,
2007; King et al., 2006).
