Biomedical Engineering Reference
In-Depth Information
lumen for nerve regeneration.
345
The low mechanical properties of collagen are
circumvented by cross-linking collagen between amine groups to create struc-
tural stability of fabricated NCs. Some of the cross-linking reagents for collagen
are glutaraldehyde, formaldehyde, and 1-ethyl-3-(3-dimethylaminopropyl)-
1-carbodiimide/
N
-hydroxysuccinimide (NHS).
345
An FDA-approved NC was
made from cross-linked bovine collagen (type I) known as NeuraGen (Integra)
tube.
336
Gelatin is derived from collagen by thermal denaturation and chemical and
physical degradation
345
into a simpler natural polymer. Gelatin is water soluble,
biocompatible, and has excellent plasticity and adhesiveness
341,343
but is lack-
ing in mechanical properties and handling characteristics. To circumvent these
issues, proper cross-linking agents are used to improve the chemical and physi-
cal characteristics of gelatin to prevent toxicity and to fabricate suitable tubular
structures for nerve regeneration.
341,343
The degree of cross-linking has been
shown to be crucial in controlling the degradation rate in order to influence
nerve regenerative responses because a too low cross-linking density results in
more degradation products to evoke more severe foreign body reaction while a
too high cross-linking density impedes the degradation and causes nerve com-
pression with thickened perineurium and epineurium.
345,347
To solve some of the issues with natural polymers that are used as biological
grafts, NCs made of biomaterials are currently used as flexible alternative.
323
The biomaterials significantly influence attachment, proliferation, and migra-
tion of endogenously regenerating cells
348
making the selection and processing
of the biomaterial critical.
349
A suitable biomaterial should possess good bio-
compatibility, appropriate degradation properties, and be amenable for control-
ling secondary NC properties such as pore size, porosity, mechanical strength,
and biological functionalization.
323
Natural and synthetic polymers have been
explored for the fabrication of NCs and some have been approved for use in
human
349
and are given on
Table 6.3
.
Nevertheless, these existing artificial NCs have limited functional capacity
to repair nerve gaps
351
sometimes resulting in complete failure of nerve regen-
eration. Improvements in the performance of NCs involve integration of neuro-
trophic factors, Schwann cells or stem cells, and luminal structures such as gels,
multiple channels, or longitudinally aligned nanofibers.
323
6.6.3 Stem Cells
One of the promising areas of research for curing various diseases especially
cancer are stem cells. Stem cells are unspecialized cells that can divide through
mitosis and can differentiate into various specialized cell types.
352
They are
capable of replenishing themselves over and over again. Stem cells are found
in all multicellular organisms and can self-renew to produce more stem cells.
Under certain physiologic or experimental conditions, they can be induced to
become tissue- or organ-specific cells with special functions. In some organs
