This preliminary research project has been conducted to evaluate different elastic polymer materials in terms of their applicability in peripheral nerve regeneration. Poly(tetrafluoroetylene-co-difluorovinylidene-co-propylene), poly(L-lactide-co-D,L-lactide), and polyurethane were used for the manufacture of tubular implants. Alginate sodium gel and fibers were used as a scaffold to fill in tube nerve grafts and enhance nerve regeneration. The tubes were implanted to reconstruct a 10 mm gap in the sciatic nerve in rats. After 3, 7, 14, 28 days the tubes were retrieved for histological examination. Among tested tubes polyurethane implants were found to be the most suitable because of their mechanical and surgical properties. Other tested implants were found to be unfavorable due to their inappropriate rigidity, elasticity or surgical convenience. Alginate transformation into dense gel form was observed that hindered inner tube space cellular colonization. In consequence of this transformation nerve regeneration was inhibited inside tube nerve grafts. Histological examination showed massive colonization of the implants with Schwann cells, and growth of new axons was found within Schwann cells growing on tubes external surface. Appropriate time rates for alginate gelation and dissolving must be determined to allow undisturbed tissue growth and maturation.
L. B. Dahlin and J. Brandt, “Basic Science of Peripheral Nerve Repair: Wallerian Degeneration/Growth Cones,” Operative Techniques in Orthopaedics, Vol. 14, No. 3, 2004, pp. 138-145. doi:10.1053/j.oto.2004.06.004
W. Z. Ray and S. E. Mackinnon, “Management of Nerve Gaps: Autografts, Allogratfs, Nerve Transfers, and End-to-End Neuroraphy,” Experimental Neurology, Vol. 223, No. 1, 2010, pp. 203-206. doi:10.1016/j.expneurol.2009.03.031
T. M. Myckatyn and S. E. Mackinnon, “Surgical Techniques of Nerve Grafting (Standard/Vascularized/Allograft),” Operative Techniques in Orthopaedics, Vol. 14, No. 3, 2004, pp. 171-178. doi:10.1053/j.oto.2004.06.007
S. Stahl and J. A. Goldenberg, “The Use of Vein Grafts in Upper Extremity Nerve Surgery,” European Journal of Plastic Surgery, Vol. 22, No. , 1999, pp. 255-259. doi:10.1007/s002380050199
G. Risitano, G. Cavallaro, T. Merrino, S. Coppolino and F. Ruggeri, “Clinical Results and Thoughts on Sensory Nerve Repair by Autologous Vein graft in Emergency Hand Reconstruction,” Chirurgie de la Main, Vol. 21, No. 3, 2002, pp. 194-197. doi:10.1016/S1297-3203(02)00109-9
D. Szarek, W. Jarmundowicz, A. Fraczek and S. Blazewicz, “Biomaterials in the Treatment of Peripheral Nerve Injuries—An Overview of Methods and Materials,” Engineering of Biomaterials, Vol. 56-57, 2006, pp. 40-53.
J. Laska, A. Fraczek, H. Yolsal, S. Blazewicz, D. Szarek, A. Sobczak and J. Chlopek, “Manufacturing and Characterization of Polimer Tubes Designer for Nerve Regeneration,” Engineering of Biomaterials, Vol. 58-60, 2006, pp. 164-165.
L. J. Chamberlain, I. V. Yannnas, A. Arrizabalaga, H.-P. Hsu, T. V. Norregaard and M. Spector, “Early Nerve Healing in Collagen and Silicone Tube Implants: Myofi-broblasts and the Cellular Response,” Biomaterials, Vol. 19, No. 15, 1998, pp. 1393-1403. doi:10.1016/S0142-9612(98)00018-0
K. Jansen, J. F. A. van der Werff, P. B. van Wachem, J. P. A. Nicolai, L. F. M. H. de Leij and M. J. A. Luyn, “A Hyaluronian-Based Nerve Guide: In Vitro Cytotoxicity, Subcutaneous Tissue Reactions, and degradation in the Rat,” Biomaterials, Vol. 25, No. 3, 2004, pp. 483-489. doi:10.1016/S0142-9612(03)00544-1
T. Nakamura, Y. Inada, S. Fukuda, M. Yoshitani, A. Nakada, S. Stoi, S. Kanemaru, K. Endo and Y. Shimizu, “Expermental Study on the Regeneration of Peripheral Nerve Gaps through a Poluglycolic Acid-Collagen (PGA-Collagen) Tube,” Brain Research, Vol. 1027, No. 1-2, 2004, pp. 18-29. doi:10.1016/j.brainres.2004.08.040
K. Matsumoto, K. Ohnishi, T. Kiyotani, T. Sekine, H. Ueda, T. Nakamura, K. Endo and Y. Shimizu, “Peripheral Nerve Regeneration across an 80-mm Gap Bridged by a Polyglicolic Acid (PGA)-Collagen Tube Filled with Laminin-Coated Collagen Fibers: A Histological and Electrophysiological Evaluation of Regenerated Nerves,” Brain Research, Vol. 868, No. 2, 2000, pp. 315-328. doi:10.1016/S0006-8993(00)02207-1
D. J. Terris, E. T. Cheng, D. S. Utley, D. M. Tarn, P.-R. Ho and A. N. Verity, “Functional Recovery Following Nerve Injury and Repair by Silicon Tubulization: Comparison of Laminin-Fibronectin, Dialyzed Plasma, Collagen Gel, and Phosphate Buffered Solution,” Auris Nasus Larynx, Vol. 26, No. 2, 1999, pp. 117-121. doi:10.1016/S0385-8146(98)00067-4
Q. Zhao, G. Lundborg, N. Danielsen, L. M. Bjursten and L. B. Dahlin, “Nerve Regeneration in a ‘Pseudo-Nerve’ Graft Created in a Silicone Tube,” Brain Research, Vol. 769, No. 1, 1997, pp. 125-134. doi:10.1016/S0006-8993(97)00620-3
A. M. Moore, R. Kasukurthi, C. K. Magill, F. Farhadi, G. H. Borschel and S. E. Mackinnon, “Limitations of Conduits in Peripheral Nerve Repairs,” Hand, Vol. 4, No. 2, 2009, pp. 180-186. doi:10.1007/s11552-008-9158-3
B. Schlosshauer, L. Dreesmann, H.-E. Schaller and N. Sinis, “Synthetic Nerve Guide Implants in Humans: A Comprehensive Survey,” Neurosurgery, Vol. 59, No. 4, 2006, pp. 740-748. doi:10.1227/01.NEU.0000235197.36789.42
H. Wang and W. C. Lineaweaver, “Nerve Conduits for Nerve Reconstruction,” Operative Techniques in Plastic and Reconstructive Surgery, Vol. 9, No. 2, 2003, pp. 59-66. doi:10.1016/S1071-0949(03)90011-4
F. J. Rodriguez, N. Gomez, G. Perego and X. Navarro, “Highly Permeable Polylactide-Caprolactone Nerve Guides Enhance Peripheral Nerve Regeneration through Long Gaps,” Biomaterials, Vol. 20, No. 16, 1999, pp. 1489-1500. doi:10.1016/S0142-9612(99)00055-1
J. Cai and X. Peng, “Permeable Guidance Channels Containing Microfilament Scaffolds Enhance Axon Growth and Maturation,” Journal of Biomedical Meterials Research Part A, Vol. 75, No. 2, 2005, pp. 374-386. doi:10.1002/jbm.a.30432
X. Navarro, E. Verdu, F. J. Rodriguez and D. Ceballos, “Artificial Nerve Graft for the Repair of Peripheral Nerve Injuries,” Neurological Sciences, Vol. 22, No. , 2001, pp. 7-13. doi:10.1007/s100720170003
S. A. Busch and J. Silver, “The Role of Extracellular Matrix in CNS Regeneration,” Current Opinion in Neurobiology, Vol. 17, No. 1, 2007, pp. 120-127. doi:10.1016/j.conb.2006.09.004
N. Terada, L. M. Bjurstem, M. Papalo?zos and G. Lundborg, “Resorbable Filament Structures as a Scaffold for Matrix Formation and Axonal Growth in Artificial Nerve Grafts: Long Term Observations,” Restorative Neurology and Neuro-science, Vol. 11, No. 1-2, 1997, pp. 65-69.
G. Lundborg, L. Dahlin, D. Dohi, M. Kanje and N. Terada, “A New Type of “Bioartificial” Nerve Graft for Bridging Extended Defects in Nerves,” The Journal of Hand Surgery, Vol. 22, No. 3, 1997, pp. 299-303. doi:10.1016/S0266-7681(97)80390-7
N. Terada, L. M. Bjursten and G. Lundborg, “The Role of Macrophages in Bioartificial Nerve Grafts Based on Resorbable Guiding Filament Structures,” Journal of Materials Science: Materials in Medicine, Vol. 8, No. 6, 1997, pp. 391-394, 1997. doi:10.1023/A:1018593219113
W. Hu, J. Gu, A. Deng and X. Gu, “Polyglycolic Acid Filaments Guide Schwann Cell Migration in Vitro and in Vivo,” Biotechnology Letters, Vol. 30, No. 11, 2008, pp. 1937-1942. doi:10.1007/s10529-008-9795-1
T. Arai, G. Lundborg and L. B. Dahlin, “Bioartificial Nerve Graft for Bridging Extended Nerve Defects in Rat Sciatic Nerve Based on Resorbable Guiding Filaments,” Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, Vol. 34, No. 2, 2000, pp. 101- 108. doi:10.1080/02844310050159936
J. L. Drury and D. J. Mooney, “Hydrogels for Tissue Engineering: Scaffold Design Variables and Applications,” Biomaterials, Vol. 24, No. 24, 2003, pp. 4337-4351. doi:10.1016/S0142-9612(03)00340-5
M. B. Bunge, K. Williams, P. M. Wood, J. Uitto and J. J. Jeffrey, “Comparison of Nerve Cell and Nerve Cell Plus Schwann Cell Cultures, with Particular Emphasis on Basal Lamina and Collagen Formation,” The Journal of Cell Biology, Vol. 84, No. 1, 1980, pp. 184-202. doi:10.1083/jcb.84.1.184
H. Fansa, W. Schneider and G. Keilhoff, “Revascularization of Tissue-Engineered Nerve Grafts and Invasion of Macrofages,” Tissue Engineering, Vol. 7, No. 5, 2001, pp. 519-524. doi:10.1089/107632701753213147
J. A. Rowley, G. Madlambayan and D. J. Mooney, “Alginate Hydrogels as Synthetic Extracellular Matrix Materials,” Biomaterials, Vol. 20, No. 1, 1999, pp. 45-53. doi:10.1016/S0142-9612(98)00107-0
R. O. Labrador, M. Buti, X. Nawarro, “Peripheral Nerve Repair: Role of Agarose Matrix Density on Functional Recovery,” Neuroreport, Vol. 6, No. 15, 1995, pp. 2022-2026. doi:10.1097/00001756-199510010-00017
T. Hashimoto, Y. Suzuki, M. Kitada, K. Kataoka, S. Wu, K. Suzuki, K. Endo, Y. Nishimura and C. Ide, “Peripheral Nerve Regeneration through Alginate Gel: Analysis of Early Outgrowth and Late Increase in Diameter of Regenerating Axons,” Experimental Brain Research, Vol. 146, No. 3, 2002, pp. 356-368. doi:10.1007/s00221-002-1173-y
S. Matsuura, T. Obara, N. Tsuchiya, Y. Suzuki and T. Habuchi, “Cavernous Nerve Regeneration by Biodegradable Alginate Gel Sponge Sheet Placement without Sutures,” Urology, Vol. 68, No. 6, 2006, pp. 1366-1371. doi:10.1016/j.urology.2006.09.051
K. Kataoka, Y. Suzuki, M Kitada, K. Ohnishi, K. Suzuki, M. Tanihara, C. Ide, K. Endo and Y. Nishimura, “Alginate, a Bioresorbable Material Derived from Brown Seaweed, Enhances Elongation of Amputated Axons of Spinal Cord in Infant Rats,” Journal of Biomedical Materials Research, Vol. 54, No. 3, 2001, pp. 373-384. doi:10.1002/1097-4636(20010305)54:3 3.0.CO;2-Q
Y. Suzuki, M. Tanihara, K. Ohnishi, K. Suzuki, K. Endo and Y. Nishimura, “Cat Peripheral Nerve Regeneration across 50 mm Gap Repaired with a Novel Guide Composed of Freeze-Dried Alginate Gel,” Neuroscience Letters, Vol. 259, No. 2, 1999, pp. 75-78. doi:10.1016/S0304-3940(98)00924-0
Y. Suzuki, M. Kitaura, S. Wu, K. Kataoka, K. Suzuki, K. Endo, Y. Ni-shimura and C. Ide, “Electophysiological and Horseradish Peroxidase-Tracing Studies of Regeneration through Alginate-Filled Gap in Adult Rat Spinal Cord,” Neuro-science Letters, Vol. 318, No. 3, 2002, pp. 121-124. doi:10.1016/S0304-3940(01)02359-X
K. Suzuki, Y. Suzuki, K. Ohnishi, K. Endo, M. Tanihara and Y. Nishimura, “Regeneration of Transected Spinal Cord in Young Adult Rats Using Freeze-Dried Alginate Gel,” Neuroreport, Vol. 10, No. 14, 1999, pp. 2891-2894. doi:10.1097/00001756-199909290-00003
K. Kataoka, Y. Suzuki, M. Kitada, T. Hashimoto, H. Chou, H. Bai, M. Ohta, S. Wu, K. Suzuki and C. Ide, “Alginate Enhances Elongation of Early Regenerating axons in Spinal Cord of Young Rats,” Tissue Engineering, Vol. 10, No. 3-4, 2004, pp. 493-504. doi:10.1089/107632704323061852
P. Pranga, R. Mullerb, A. Eljaouharib, K. Heckmannb, W. Kunzb, T. Weberc, C. Faberc, M. Vroemena, U. Bogdahna and N. Weidnera, “The Promotion of Oriented Axonal Regrowth in the Injured Spinal Cord by Alginate-Based Anisotropic Capillary Hydrogels,” Biomaterials, Vol. 27, No. 19, 2006, pp. 3560-3569.
J. R. Dijkstra, M. F. Meek, P. H. Robinson and A. Gramsbergen, “Methods to Evaluate Functional Nerve recovery in Adult Rats: Walking Track Analysis, Video Analysis and the Withdrawal Reflex,” Journal of Neuroscience Methods, Vol. 96, No. 2, 2000, pp. 89-96. doi:10.1016/S0165-0270(99)00174-0
R. Koka and T. A. Hadlock, “Brief Communication Quantification of Functional Recovery Following Rat Sciatic Nerve Transaction,” Experimental Neurology, Vol. 168, No. 1, 2001, pp. 192-195. doi:10.1006/exnr.2000.7600
A. E. Beris, K. K. Naka, A. Skopelitou, I. Kosta, V. Vragalas, S. Konitsiotis, E. Bontioti and P. N. Soucacos, “Functional Assessment of the Rat Sciatic Nerve Following Intraoperative Expansion: The Effect of Recovery Duration on Behavioural, Neurophysiological, and Morphological Measures,” Microsurgery, Vol. 17, No. 10, 1996, pp. 568577. doi:10.1002/(SICI)1098-2752(1996)17:10 3.0.CO;2-M
C. L. A. M. Vleggeert-Lankamp, “The Role of Evaluation Methods in the Assessment of Peripheral Nerve Regeneration through Synthetic Conduits: A Systematic Review,” Journal of Neurosurgery, Vol. 107, No. 6, 2007, pp. 1168-1189. doi:10.3171/JNS-07/12/1168
M. F. Meek, P. H. Robinson, I. Stokroos, E. H. Blaauw, G. Kors and W. F. A. den Dunne, “Electronmicroscopical Evaluation of Short-Term Nerve Regeneration through a Thin-Walled Biodegradable Poly(DLLA-ε-CL) Nerve Guide Filled with Modified Denatured Muscle Tissue,” Biomaterials, Vol. 22, No. 10, 2001, pp. 1177-1185. doi:10.1016/S0142-9612(00)00340-9
K. H. Bouhadir, K. Y. Lee, E. Alsberg, K. L. Damm, K. W. Anderson and D. J. Mooney, “Degradation of Partially Oxidized Alginate and Its Potential Application for Tissue Engineering,” Biotechnology Progress, Vol.17 , No. 5, 2001, pp. 945-950. doi:10.1021/bp010070p
M. S. Shoichet, R. H. Li, M. L. White and S. R. Winn, “Stability of Hydrogels Used in Cell Encapsulation: An in Vitro Comparison of Alginate and Agarose,” Biotechnology and Bioengineering, Vol. 50, No. 4, 1996, pp. 374-381. doi:10.1002/(SICI)1097-0290(19960520)50:4 3.0.CO;2-I
T. Hausner, R. Schmidhammer, S. Zandieh, R. Hopf, A. Schultz, S Gogolewski, H. Hertz and H. Redl, “Nerve Regeneration Using Tubular Scaffolds from Biodegradable Polyurethane,” Acta Neurochirurgica Supplementum (How to Improve the Results of Peripheral Nerve Surgery), Vol. 100, 2007, pp. 69-72.
G. Stoll, J. W. Griffin, C. Y. Li and B. D. Trapp, “Wallerian Degeneration in the Peripheral Nervous System: Participation of Both Schwann Cells and Macrophages in Myelin Degradation,” Journal of Neurocytology, Vol. 18, No. 5, 1989, pp. 671-683. doi:10.1007/BF01187086
W. Brück, “The Role of Macrophages in Wallerian Degeneration,” Brain Pathology, Vol. 7, No. 2, 1997, pp. 741-752. doi:10.1111/j.1750-3639.1997.tb01060.x
L. R. Williams, F. M. Longo, H. C. Powell, G. Lundborg and S. Varon, “Spatial-Temporal Progress of Peripheral Nerve Regeneration within a Silicone Chamber: Parameters for Bioassay,” The Journal of Comparative Neurology, Vol. 218, No. 4, 1983, pp. 460-470. doi:10.1002/cne.902180409
J. M. Le Beau, M. H. Ellisman and H. C. Powell, “Ultrastructural amd Morphometric Analysis of Long-Term Peripheral Nerve Regeneration through Silicone Tubes,” Journal of Neurocytology, Vol. 17, No. 2, 1988, pp. 161- 172. doi:10.1007/BF01674203