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Another strategy to support SC colonization inside nerve guides is pre-
enrichment of the conduit with SCs or their precursors. BMSC-derived SCs
have been used in combination with chitosan conduits to repair 12-mm rat
sciatic nerve gap, resulting in nerve conduction velocities, average
regenerated myelin area, and number of myelinated axons similar to those
conduits treated with sciatic nerve-derived SCs ( Ao et al., 2011 ).
Chitosan-based conduits combined with autologous BMSCs have been
successfully utilized to bridge 8-mm-long sciatic nerve defects in adult rats
( Zheng & Cui, 2012 ).
Chitosan/PLGA-based neuronal scaffolds, in which autologous BMSCs
have been incorporated, promoted dog sciatic nerve regeneration and func-
tional recovery across 50- to 60-mm-long gaps. The outcome was close to
that of nerve autografts and better than that of chitosan/PLGA-based scaf-
folds alone ( Ding et al., 2010; Xue et al., 2012 ).
Very recently, chitosan/PLGA nerve grafts combined with autologous
BMSCs have been utilized to bridge 50-mm-long medial nerve defects in
rhesus monkeys. Functional recovery was more efficient when chitosan/
PLGA nerve grafts were combined with BMSCs instead of the used cell-free
chitosan/PLGA grafts. Moreover, blood tests and histopathological exami-
nations demonstrated that BMSCs could be safely used in primates
( Hu et al., 2013 ).
Recently, combination of peptide and cells to enhance nerve regeneration
has been used to bridge 10-mm gap lesion in rat sciatic nerve. Laminin-coated
chitosan conduit in combination with BMSCs results in enhancement of
nerve regrowth, muscle mass maintaining, and functional recovery. BMSCs
inhibited neuronal cell death and overturn the inflammatory response induced
by long-term chitosan implantation promoting nerve regeneration ( Hsu
et al., 2013 ).
Chitosan 3-glycidoxypropyl-methyldiethoxysilane-cross-linked mem-
branes have been used for peripheral nerve reconstruction in the rat sciatic
nerve model, either alone or in combination with N1E-115 NSCs. Chitosan
membranes showed good biocompatibility and were suitable for N1E-115
cells growth. However, the study of in vivo nerve regeneration after nerve
crush injury showed that freeze-dried chitosan membrane without cell
enrichment improved axonal regrowth and functional recovery, suggesting
that nerve enwrapping with chitosan membrane alone may be an effective
method for improving peripheral nerve repair, while enrichment with
N1E-115 neural cells is not ( Amado et al., 2008; Simoes et al., 2011 ).
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