Biomedical Engineering Reference
In-Depth Information
This vicious cycle can result in significant neuronal loss in the CNS and is
extremely devastating given the non-proliferative status of neurons.
2.2.
Design challenges and biomaterials for neural engineering
A consensus within the field of neural tissue engineering supports a multi-faceted
approach that addresses the numerous biologic events following injury to the
CNS or PNS. In the CNS, the challenges are substantial: containment of
secondary injury and recapitulation of development. In contrast, the PNS is
already primed for regeneration but the quality of regeneration is poor.
Therapeutic objectives should strive to accelerate the regenerative process and
minimize aberrant reinnervation. In either scenario, instructional biomaterials
can address some of these issues and provide a platform for cell or drug delivery.
In addition to manufacturing ease and scalability, neural biomaterials should in
general, satisfy the following criteria:
i)
Integrate with host tissue and encourage cell-specific attachment, migration
and growth:
Host integration is key in minimizing the foreign body response
and for promoting cell-specific interactions
in vivo
. In the PNS, proper
neuron-biomaterial as well as Schwann cell -substrate interactions are
critical in dictating biomaterial success. Ideal substrates should encourage
Schwann cell attachment, migration and also facilitate axon pathfinding.
Additionally, discouraging fibroblast adhesion will reduce intrafascicular
scarring. In the CNS, minimization of astrocyte attachment and proliferation
is vital to diminishing glial scars, whereas neurons should readily adhere and
elongate along the biomaterial.
ii)
Provide directional cues for guided axonal extension:
Controlled axonal
targeting is key to successful functional reconnection. In the PNS, axonal
projection in the distal direction will reduce the likelihood of aberrant
regeneration and neuroma formation. Within the spinal cord, white matter
destruction is the primary culprit leading to paralysis. Likewise, axon growth
that emulates the original rostral-caudal anatomy is preferred.
iii)
Suppress the inhibitors of regeneration or stimulate regeneration (especially
in the CNS):
Biomaterials will need to either stimulate nerve regeneration or
negate the growth inhibiting microenvironment following CNS injury.
Pharmaceutics aimed to mitigate inflammation and secondary injury are
further warranted. If significant neural tissue is lost, cellular therapies that
involve harvesting cells,
in vitro
expansion and reintroduction into the lesion
may be necessary. Facilitating PNS regeneration via additional presentation
of trophic support may also accelerate distal target reinnervation.
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