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Neurotrophic factors were supplemented at the injury site functional outcomes in long‑term experiments. Given their
using a mini‑osmotic pump and no effect was observed abundance and plasticity, we personally consider these
at low doses. Conversely, very high concentrations cells to be one of the main options in future nerve repair
[3]
of BDNF inhibited the axonal regeneration, with a studies. In this review, we have attempted to present a
mechanism that seemed to be dose‑dependent. In complete tableau of the different components which
addition, a combination of BDNF and GDNF resulted in we believe are relevant for successful regeneration. To
better nerve repair. Madduri et al. [70,71] tested instead the perform at their best, transplanted cells need a favorable
[3]
efficiency of cross‑linked NGF and GDNF as single growth environment, with proper attachment to biomaterials and
factors or in combination to repair peripheral nerve directionality driven through conduits. If present, the
injuries, resulting in enhanced early regeneration after external delivery of growth factors should be controlled
two weeks postimplantation and higher SC migration. to avoid inhibitory effects on regeneration. This would
Since neurotrophic factors are gradually released in the support both transplanted and native Schwann cell
regenerative environment by cells as a response to the performance, improving nerve regeneration. The stronger
natural events occurring during Wallerian degeneration and mechanical stability shown by cells seeded on an ECM
axon regeneration and myelination, it may be beneficial such as FN and LM may be essential for cell migration and
to recreate a molecular gradient along the inner surface control of local signaling environment. The influence
[36]
of the NGC, guaranteeing the necessary supply of factors of cell behavior on material coatings is an interesting
to support the regeneration process. An in vitro study question, as this effect is not dependent upon an
demonstrated that a patterned gradient of immobilized external delivery source (as in the case of growth factors).
NGF on chitosan substrates would increase axon Similarly, interactions between cells and biomaterials may
sprouting and branching in the direction of the gradient influence cell performance and directionality, making it an
itself. Tang et al. were also able to control the gradient interesting field for future research.
[13]
[72]
distribution of NGF along a poly(ε‑caprolactone)‑block‑p
oly(L‑lactic acid‑co‑ε‑caprolactone) conduit and observed ACKNOWLEDGMENTS
a higher sciatic function index (SFI) when compared to
uniform distribution of the neurotrophic factor. The authors are grateful to the Swiss National Found for
The ECM‑matrix inclusion of growth factors that are supporting their current research. P.G. di Summa is thankful
gradually released in the inner lumen of the NGCs to the SICPA foundation and the University Hospital of
have also been considered to be a valuable alternative Lausanne (CHUV) for supporting his hand surgery training and
for the optimization of the bioengineered construct. research in peripheral nerve injury and regeneration.
A successful study was presented by Cao et al., during
[73]
which collagen scaffolds were loaded with an LM filler REFERENCES
containing CNTF, promoting high levels of myelination
after twelve weeks postimplantation and enhancing both 1. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief
review. Neurosurg Focus 2004;16:E1.
SFI and nerve conduction velocity. 2. Geuna S, Raimondo S, Ronchi G, Di Scipio F, Tos P, Czaja K, Fornaro M.
Chapter 3: histology of the peripheral nerve and changes occurring during
Cell transduction can also be thought of as an alternative nerve regeneration. Int Rev Neurobiol 2009;87:27‑46.
approach to release specific growth factors at the site 3. Gordon T. The role of neurotrophic factors in nerve regeneration.
[40]
of regeneration. Godinho et al. implanted peripheral Neurosurg Focus 2009;26:E3.
nerve grafts containing SC expressing BDNF, CTNF, and 4. Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach
NT‑3, respectively, resulting in different outcomes as to peripheral nerve regeneration: bridging the peripheral nerve gap and
a function of the growth factor. Following accurate 5. enhancing functional recovery. J R Soc Interface 2012;9:202‑21.
Geuna S, Tos P, Titolo P, Ciclamini D, Beningo T, Battiston B. Update on nerve
locomotor investigation by using the gait analysis system repair by biological tubulization. J Brachial Plex Peripher Nerve Inj 2014;9:1‑6.
® [74‑76]
Catwalk , they showed a significant improvement of 6. Nectow AR, Marra KG, Kaplan DL. Biomaterials for the development of
functional recovery under CTNF and NT‑3 conditions while peripheral nerve guidance conduits. Tissue Eng Part B Rev 2012;18:40‑50.
NT‑3 stimulated a higher degree of myelination. [40] 7. Hoffman‑Kim D, Mitchel JA, Bellamkonda RV. Topography, cell response,
and nerve regeneration. Annu Rev Biomed Eng 2010;12:203‑31.
8. Cunha C, Panseri S, Antonini S. Emerging nanotechnology approaches in tissue
CONCLUSION AND FUTURE engineering for peripheral nerve regeneration. Nanomedicine 2011;7:50‑9.
DIRECTIONS 9. Sun M, McGowan M, Kingham PJ, Terenghi G, Downes S. Novel thin‑walled
nerve conduit with microgrooved surface patterns for enhanced peripheral
nerve repair. J Mater Sci Mater Med 2010;21:2765‑74.
Despite advancements in microsurgical techniques, 10. Mitchel JA, Hoffman‑Kim D. Cellular scale anisotropic topography guides
nerve repair clinically provides suboptimal results, and Schwann cell motility. Plos One 2011;6:e24316.
autologous nerve grafts are the primary choice for nerve 11. Mobasseri SA, Terenghi G, Downes S. Micro‑structural geometry of thin
reconstruction, especially over long gaps. This opens films intended for the inner lumen of nerve conduits affects nerve repair.
J Mater Sci Mater Med 2013;24:1639‑47.
the field for research and the development of tissue 12. Madduri S, Papaloizos M, Gander B. Trophically and topographically
engineered nerve guides [Figure 1]. The transplant of functionalized silk fibroin nerve conduits for guided peripheral nerve
regenerative cells into biodegradable conduits could be regeneration. Biomaterials 2010;31:2323‑34.
a clinical tool translating into improved regeneration. 13. Yu LM, Miller FD, Shoichet MS. The use of immobilized neurotrophins to
In our experience, [47,49,58] ASCs contribute to axonal support neuron survival and guide nerve fiber growth in compartmentalized
chambers. Biomaterials 2010;31:6987‑99.
regeneration and myelination with the improvement of 14. Mukhatyar V, Pai B, Clements I, Srinivasan A, Huber R, Mehta A,
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