Question

4. Neural regeneration:

1. Explain why the central nervous system has so much difficulty with regeneration following an injury. Include at least two specific reasons.
2. Explain the rationale for using electrically conductive materials for neural regeneration.
3. Explain the rationale for using nanomaterials for neural regeneration.
4. Explain the rationale for incorporating peptides derived from extracellular matrix proteins into scaffolds for neural regeneration. List at least three potential benefits.
5. List at least two endpoints that you would look at microscopically to determine whether neural regeneration has taken place.
6. List at least two endpoints that you would look at clinically to determine whether neural regeneration has taken place.
7. Can you think of another potential biomedical application of electrically conducting polymers? Explain your answer. Numerous answers will be accepted for this question.

Answer 1

Answers:

a) Axon regeneration in the mature mammalian central nervous system (CNS) is extremely limited after injury. adult mammalian CNS neurons normally do not regenerate. The reaction of the nervous tissue to any injury leading to scar tissue formation acts as a barrier for regeneration in the CNS,

The two major classes of CNS regeneration inhibitors are the myelin-associated inhibitors (MAIs) and the chondroitin sulfate proteoglycans (CSPGs). These molecules limit axon regeneration, and, by interfering with their function Cell-autonomous factors are also important determinants of CNS regeneration failure. CNS neurons do not upregulate growth-associated genes to the same extent as do PNS neurons. Consequently, their ability to regenerate is limited even in the absence of inhibitors. Increasing the intrinsic growth capacity of neurons allows modest axon regeneration within the CNS

b) To achieve complete functional recovery of injured neural tissue, approaches seek to develop a material construct that combines several cues to modulate cell behavior, whether it be to guide regenerating axons to reconnect with target tissue or to elicit migration and growth factor release by support cells. Cells respond to cues in the microenvironment.

c) By mimicking several unique characteristics of the natural environment of cells, synthetic materials for neural regeneration can be improved chemically and biologically. Especially bioactivation of materials can be achieved by the addition of small chemical moieties to the scaffold particularly found in specific tissues or addition of biologically active molecules derived from natural ECM. The ECM‐derived short peptides are promising candidates to be presented as functional domains on the scaffold surface for use in neural regeneration.

d) The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. The natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells.

e) Assessing nerve integrity and myelination after the injury is necessary to provide insight into nerve fiber counts and the degree of myelination to determine nerve viability.

f)Tacrolimus (immunosuppressant) and electrical stimulation are commonly used for other reconstructive indications and as such, are both readily available clinically.

g) Conducting polymers have been widely used in biomedical applications such as biosensors and tissue engineering.

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