Directory UMM :Data Elmu:jurnal:B:Brain Research:Vol888.Issue1.2001:
Brain Research 888 (2001) 158–162
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Short communication
Peripheral nerve regeneration along collagen filaments
Satoru Yoshii a , *, Masanori Oka b
b
a
Institute of Biomedical Engineering, Kansai Denryoku Hospital, Imaichi 2 -7 -14, Asahi-ku, Osaka 535 -0011, Japan
Department of Tissue Regeneration, Field of Clinical Application, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
Accepted 19 September 2000
Abstract
This paper describes the regeneration of severed peripheral nerve axons along collagen filaments without a tube. Two thousand collagen
filaments were grafted to bridge 20 mm defects of rat sciatic nerve. The number of myelinated axons was approximately 4800 in the distal
end of the nerve autograft at 8 weeks postoperatively; while in the collagen-filaments nerve guide it was 5500. The results suggested the
collagen filaments guided regenerating axons effectively. 2001 Elsevier Science B.V. All rights reserved.
Theme: Development and regeneration
Topic: Regeneration
Keywords: Nerve; Peripheral; Regeneration; Axon; Collagen; Filament
Axonal regeneration has been studied using a tubular
prosthesis for a long time. Entubulation repair has a
lengthy history and several experimental and clinical
studies have explored the effectiveness of many biodegradable and non-biodegradable materials with or without
some protein additives and cells [1,2,4–10,14,15,17–
22,24,25,27]. It has been reported that increased permeability—extent of exposure to surrounding tissue—improves axonal regeneration [11–13,16]. We developed a
nerve guide made of collagen filaments, instead of a tube,
to improve resorbability and permeability of the material
employed and assessed its effect in peripheral nerve
regeneration. The nerve guides made of collagen filaments
were provided by Koken Co. Ltd., (Tokyo, Japan). The
collagen filament, 20 mm in diameter, was made of highly
purified type I collagen. Bovine skin was subjected to
enzymatic and chemical treatments to remove non-collagenous components. The collagen filament was stabilized
using polyethylene glycol diglycidyl ether as the crosslinking reagent, which cross-linked ´-NH 2 groups of
collagen molecules. The cross-linked collagen is resorbed
more slowly compared to the non cross-linked collagen
and resists bacterial collagenase digestion. The use of
*Corresponding author. Tel.: 181-6-6956-2729; fax: 181-6-64586994.
E-mail address: k-20433@kepco.co.jp (S. Yoshii).
polyethylene glycol diglycidyl ether as the cross-linking
reagent does not elicit the macrophage response. The
collagen filament was further stabilized using ultraviolet
radiation (250 nm, 30 W, 30 min). Two-thousand collagen
filaments were used to make a 22-mm-long nerve guide
(Fig. 1). Twenty-two millimeter long collagen tube (internal diameter 1.8 mm, wall thickness 50 mm) was made and
used as a control.
Thirty-nine 6-month-old male Wistar rats weighing
about 250 g were used for the study. Adequate measures
were taken to minimize pain or discomfort. Experiments
were carried out in accordance with the European Communities Council Directive of 24 November 1986. Under
deep pentobarbital anesthesia, the right sciatic nerve was
exposed from the sciatic notch to the popliteal region, and
a 20-mm segment of the tibial division of the nerve was
removed. The proximal and distal nerve stumps were
sutured to the 20-mm long sciatic nerve autograft with two
sutures using 10-0 monofilament nylon epineurial sutures
to bridge the nerve defect in Autograft Group. The
proximal and distal nerve stumps were sutured to the
collagen-filament nerve guide with two sutures using 10-0
monofilament nylon epineurial sutures to bridge the nerve
defect in the Fiber Group. The proximal and distal nerve
stumps were inserted 1 mm into the collagen tubes and
were held in place with two epineurial sutures in the Tube
Group. Fifteen rats received a sciatic nerve autograft
0006-8993 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved.
PII: S0006-8993( 00 )03025-0
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
159
Fig. 1. Collagen-filaments nerve guide. Two-thousand collagen filaments were used to make a 22-mm long nerve guide.
(Autograft Group) and another group of 15 rats underwent
implantation of nerve guides made of collagen filaments
(Fiber Group). Nine rats underwent implantation of collagen tubes (Tube Group). In the Fiber Group, three of the
removed sciatic nerves were examined histologically as the
normal control.
Motor function was assessed for 12 weeks at 4-week
intervals using the sciatic functional index (SFI). Three
rats in each group underwent the assessment. Hind feet
were wiped with India ink and the rat walked down a
walking track. Pawprints were measured for both the
operated and unoperated sides. The values were submitted
to a sciatic functional index as described by Bain et al. [3].
Axonal regeneration across the repair site was electrophysiologically evaluated at 4, 8 and 12 weeks postoperatively using nine rats in each group. Before removal of the
nerve, bipolar stimulating electrodes were inserted into the
planter surface of the foot in the receptive area of the
sciatic nerve. The previously operated sciatic nerve was
exposed and recording electrodes were placed on the
sciatic nerve 3 mm proximal and 3 mm distal to the repair
site. The latency was measured and the nerve conduction
velocity was calculated (Electronic stimulator SEN-3201,
Dual-beam memory oscilloscope VC-10, Add scope
ATAC-210, Nihon Kohden, Japan). In addition to conduction velocity, the sciatic nerve was stimulated proximal
and distal to the repair site using two pairs of electrodes,
and a needle electromyogram (EMG) was recorded from
the short flexor muscles of the foot.
At 4 and 8 weeks postoperatively, six rats in the
Autograft and Fiber Groups, and three rats in the Tube
Group were sacrificed. Twenty-five millimeter-long sciatic
nerves including the nerve guides or autografts were
dissected out, fixed in 2.5% glutaraldehyde and postfixed
in 2% osmium tetroxide. Each nerve was embedded in
100% Epon. One micrometer thick transverse sections
were made from the nerve to obtain sections at successive
two-millimeter intervals. Each section was stained with
toluidine blue and examined under a light microscope.
Ultrathin sections of selected areas of the nerves were
examined under an electron microscope (Nihon Denshi
JEM 200cx, Tokyo, Japan) at 100 kV.
The axonal count and fiber diameter were used to
evaluate axonal regeneration. The selected sections were
photographed under a light microscope (original magnification 3400, enlarged to 31000). Montages of whole
section were constructed. All myelinated axons were
counted and the fiber diameter was measured. The number
of axons in the tibial division of the sciatic nerve of normal
rats was approximately 5200 (52306360), and the diameter was 6.9 mm. The dissected nerve guides in the Fiber
Group were brown-colored at 4 weeks postoperatively and
their mean diameter was 2.4 mm, which was larger than
that of the grafted tibial division of the sciatic nerve (mean
diameter 1.1 mm). The dissected collagen tubes were
brown-colored and semitransparent in Tube Group. In all
collagen tubes, proximal stumps had small outgrowth
extending less than 6 mm. Neuromas were found at both
ends of the all six autografts in the Autograft Group at 4
weeks postoperatively. No neuroma was found at the
suture in the Fiber Group. Regenerated unmyelinated
axons were found, but no regenerated myelinated axon was
found at the distal end of the graft—1 mm proximal to the
distal suture threads—in both the Autograft Group and the
160
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
Fig. 2. Electron micrographs at the distal end of the nerve autograft and collagen nerve guide. Cross sections at the distal end of the autograft (a) and
collagen-filament nerve guide (b) at 8 weeks postoperatively. Arrow heads indicate myelinated axons and arrows indicate the residues of collagen
filaments. (Original magnification31000, scale bar: 10 mm.)
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
Fiber Group at 4 weeks postoperatively. The distal ends of
the regenerated myelinated axons were found at 10–14
mm distal to the proximal suture threads in the Autograft
Group at 4 weeks postoperatively. The distal ends of the
regenerated myelinated axons were found at 12–16 mm
distal to the proximal suture threads in the Fiber Group.
The distal ends of the regenerated myelinated axons were
found at 2–4 mm distal to the proximal suture threads in
the Tube Group. Under the electron microscope, many
macrophages were found around the collagen material to
phagocytose it in the Fiber Group and the Tube Group at 4
weeks postoperatively.
The dissected nerve guides in the Fiber Group were
white-colored at 8 weeks postoperatively and their mean
diameter was 1.8 mm, which was larger than that of the
grafted tibial division of the sciatic nerve (1.1 mm) in the
Autograft Group. No neuroma was found at the suture in
the Autograft and Fiber Groups at 8 weeks postoperatively.
The collagen tubes were not found in all three rats and a
very thin white structure linked the nerve stumps in the
Tube Group. Regenerated myelinated and unmyelinated
axons were found at the distal end of the graft—1 mm
proximal to the distal suture threads—in both the Autograft
Group and the Fiber Group at 8 weeks postoperatively
(Fig. 2a,b). The mean number of myelinated axons was
approximately 4800 (48376604) in the distal end of the
nerve autograft (Autograft Group, six rats) at 8 weeks
postoperatively; while in the distal end of the collagenfilaments nerve guide (Fiber Group, six rats) it was
approximately 5500 (54916617). There were no statistically significant differences between groups (Wilcoxon’s
tests, P50.05). The mean fiber diameter was 3.3 mm in the
distal end of the nerve autograft at 8 weeks postoperatively; while in the distal end of the nerve guide it was 2.3
mm. The mean fiber diameter was significantly larger in
the Autograft Group (Student’s t-test, P50.05). No myelinated and unmyelinated axon was found in the thin white
structure in the Tube Group. Small residues of collagen
filaments were found among regenerated axons in the Fiber
Group (Fig. 2b). Few macrophages were found around the
collagen filaments.
The SFI values decreased after the nerve transection and
repair. The mean SFI values for the rats in the Autograft
Group was 2106.4 at 4 weeks postoperatively. The value
was 2121.5 in the Fiber Group. The value was 2117.2 in
the Tube Group. The values did not increase in all groups
at 8 weeks postoperatively. The values increased slightly
in all groups at 12 weeks postoperatively. The mean SFI
values for the rats in the Autograft Group was 271.0 at 12
weeks postoperatively. The value was 284.2 in the Fiber
Group. The value was 2105.8 in the Tube Group. The
three groups were considered to be not different practically
in SFI values. Toe contracture was not found in all groups
through the experimental period.
No interpretable compound action potential was recorded in all groups at 4 and 8 weeks postoperatively. No
161
EMG was recorded from the short muscles of the foot in
all groups at 4 and 8 weeks postoperatively. Interpretable
compound action potentials were recorded for two out of
three rats in the Autograft Group and two out of three rats
in the Fiber Group at 12 weeks postoperatively. The mean
nerve conduction velocity was 51.7 m / s for the Autograft
Group and 40.0 m / s for the Fiber Group. In all six rats
from the Autograft and Fiber Groups, good EMG was
recorded from the short flexor muscles of the foot when
the nerve was stimulated proximal or distal to the repair
site. No interpretable compound action potential or no
EMG from the short muscles of the foot was recorded in
the Tube Group at 12 weeks postoperatively.
Myelinated axons of the rat sciatic nerve had regenerated 20 mm along collagen-filaments without a tube or
neurotrophic additives by 8 weeks postoperatively in this
study. It has been reported that increased permeability
improves axonal regeneration [11–13,16]. Yoshii et al.
reported that they had obtained good regeneration of axons
using a nerve guide which was made of laminin-coated
filaments, instead of a tube [26]. A nerve guide made of
filaments without a tube has high permeability. In our
study, the number of myelinated axons of the tibial
division of the normal sciatic nerve was smaller than the
previously reported one [23]. This may be due to differences in staining and counting methods. The number of
regenerated myelinated axons in the collagen-filaments
nerve guide was not smaller than the number of regenerated myelinated axons in the nerve autograft. The mean
fiber diameter and mean nerve conduction velocity were
significantly less in the collagen-filaments nerve guide
group than those in the Autograft Group at 8 weeks
postoperatively. A study with an extended period should
be made to investigate these findings. The collagen filaments were considered easy to resorb because only small
residues of collagen filaments were found among regenerated axons at 8 weeks postoperatively (Fig. 2b).
References
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[13] D.H. Kim, S.E. Connolly, S. Zhao, R.W. Beuerman, R.M. Voorhies,
D.G. Kline, Comparison of macropore, semipermeable, and nonpermeable collagen conduits in nerve repair, J. Reconst. Microsurg.
9 (1993) 415–420.
[14] D.G. Kline, G.J. Hayes, The use of a resorbable wrapper for
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[15] R.A.W. Lehman, G.J. Hayes, Degeneration and regeneration in
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[16] F.M. Longo, M. Manthorpe, S.D. Skapper, G. Lundborg, S. Varon,
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[17] G. Lundborg, L.B. Dahlin, N.P. Danielsen, H.A. Hansson, K.
Larsson, Reorganization and orientation of regenerating nerve fibers,
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(1981) 265–281.
[18] G. Lundborg, L.B. Dahlin, N.P. Danielsen, R.H. Gelberman, F.M.
Longo, H.C. Powell, S. Varon, Nerve regeneration in silicone
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[19] R.D. Madison, C.F. Da Silva, P. Dikkes, Entubulation repair with
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www.elsevier.com / locate / bres
Short communication
Peripheral nerve regeneration along collagen filaments
Satoru Yoshii a , *, Masanori Oka b
b
a
Institute of Biomedical Engineering, Kansai Denryoku Hospital, Imaichi 2 -7 -14, Asahi-ku, Osaka 535 -0011, Japan
Department of Tissue Regeneration, Field of Clinical Application, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
Accepted 19 September 2000
Abstract
This paper describes the regeneration of severed peripheral nerve axons along collagen filaments without a tube. Two thousand collagen
filaments were grafted to bridge 20 mm defects of rat sciatic nerve. The number of myelinated axons was approximately 4800 in the distal
end of the nerve autograft at 8 weeks postoperatively; while in the collagen-filaments nerve guide it was 5500. The results suggested the
collagen filaments guided regenerating axons effectively. 2001 Elsevier Science B.V. All rights reserved.
Theme: Development and regeneration
Topic: Regeneration
Keywords: Nerve; Peripheral; Regeneration; Axon; Collagen; Filament
Axonal regeneration has been studied using a tubular
prosthesis for a long time. Entubulation repair has a
lengthy history and several experimental and clinical
studies have explored the effectiveness of many biodegradable and non-biodegradable materials with or without
some protein additives and cells [1,2,4–10,14,15,17–
22,24,25,27]. It has been reported that increased permeability—extent of exposure to surrounding tissue—improves axonal regeneration [11–13,16]. We developed a
nerve guide made of collagen filaments, instead of a tube,
to improve resorbability and permeability of the material
employed and assessed its effect in peripheral nerve
regeneration. The nerve guides made of collagen filaments
were provided by Koken Co. Ltd., (Tokyo, Japan). The
collagen filament, 20 mm in diameter, was made of highly
purified type I collagen. Bovine skin was subjected to
enzymatic and chemical treatments to remove non-collagenous components. The collagen filament was stabilized
using polyethylene glycol diglycidyl ether as the crosslinking reagent, which cross-linked ´-NH 2 groups of
collagen molecules. The cross-linked collagen is resorbed
more slowly compared to the non cross-linked collagen
and resists bacterial collagenase digestion. The use of
*Corresponding author. Tel.: 181-6-6956-2729; fax: 181-6-64586994.
E-mail address: k-20433@kepco.co.jp (S. Yoshii).
polyethylene glycol diglycidyl ether as the cross-linking
reagent does not elicit the macrophage response. The
collagen filament was further stabilized using ultraviolet
radiation (250 nm, 30 W, 30 min). Two-thousand collagen
filaments were used to make a 22-mm-long nerve guide
(Fig. 1). Twenty-two millimeter long collagen tube (internal diameter 1.8 mm, wall thickness 50 mm) was made and
used as a control.
Thirty-nine 6-month-old male Wistar rats weighing
about 250 g were used for the study. Adequate measures
were taken to minimize pain or discomfort. Experiments
were carried out in accordance with the European Communities Council Directive of 24 November 1986. Under
deep pentobarbital anesthesia, the right sciatic nerve was
exposed from the sciatic notch to the popliteal region, and
a 20-mm segment of the tibial division of the nerve was
removed. The proximal and distal nerve stumps were
sutured to the 20-mm long sciatic nerve autograft with two
sutures using 10-0 monofilament nylon epineurial sutures
to bridge the nerve defect in Autograft Group. The
proximal and distal nerve stumps were sutured to the
collagen-filament nerve guide with two sutures using 10-0
monofilament nylon epineurial sutures to bridge the nerve
defect in the Fiber Group. The proximal and distal nerve
stumps were inserted 1 mm into the collagen tubes and
were held in place with two epineurial sutures in the Tube
Group. Fifteen rats received a sciatic nerve autograft
0006-8993 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved.
PII: S0006-8993( 00 )03025-0
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
159
Fig. 1. Collagen-filaments nerve guide. Two-thousand collagen filaments were used to make a 22-mm long nerve guide.
(Autograft Group) and another group of 15 rats underwent
implantation of nerve guides made of collagen filaments
(Fiber Group). Nine rats underwent implantation of collagen tubes (Tube Group). In the Fiber Group, three of the
removed sciatic nerves were examined histologically as the
normal control.
Motor function was assessed for 12 weeks at 4-week
intervals using the sciatic functional index (SFI). Three
rats in each group underwent the assessment. Hind feet
were wiped with India ink and the rat walked down a
walking track. Pawprints were measured for both the
operated and unoperated sides. The values were submitted
to a sciatic functional index as described by Bain et al. [3].
Axonal regeneration across the repair site was electrophysiologically evaluated at 4, 8 and 12 weeks postoperatively using nine rats in each group. Before removal of the
nerve, bipolar stimulating electrodes were inserted into the
planter surface of the foot in the receptive area of the
sciatic nerve. The previously operated sciatic nerve was
exposed and recording electrodes were placed on the
sciatic nerve 3 mm proximal and 3 mm distal to the repair
site. The latency was measured and the nerve conduction
velocity was calculated (Electronic stimulator SEN-3201,
Dual-beam memory oscilloscope VC-10, Add scope
ATAC-210, Nihon Kohden, Japan). In addition to conduction velocity, the sciatic nerve was stimulated proximal
and distal to the repair site using two pairs of electrodes,
and a needle electromyogram (EMG) was recorded from
the short flexor muscles of the foot.
At 4 and 8 weeks postoperatively, six rats in the
Autograft and Fiber Groups, and three rats in the Tube
Group were sacrificed. Twenty-five millimeter-long sciatic
nerves including the nerve guides or autografts were
dissected out, fixed in 2.5% glutaraldehyde and postfixed
in 2% osmium tetroxide. Each nerve was embedded in
100% Epon. One micrometer thick transverse sections
were made from the nerve to obtain sections at successive
two-millimeter intervals. Each section was stained with
toluidine blue and examined under a light microscope.
Ultrathin sections of selected areas of the nerves were
examined under an electron microscope (Nihon Denshi
JEM 200cx, Tokyo, Japan) at 100 kV.
The axonal count and fiber diameter were used to
evaluate axonal regeneration. The selected sections were
photographed under a light microscope (original magnification 3400, enlarged to 31000). Montages of whole
section were constructed. All myelinated axons were
counted and the fiber diameter was measured. The number
of axons in the tibial division of the sciatic nerve of normal
rats was approximately 5200 (52306360), and the diameter was 6.9 mm. The dissected nerve guides in the Fiber
Group were brown-colored at 4 weeks postoperatively and
their mean diameter was 2.4 mm, which was larger than
that of the grafted tibial division of the sciatic nerve (mean
diameter 1.1 mm). The dissected collagen tubes were
brown-colored and semitransparent in Tube Group. In all
collagen tubes, proximal stumps had small outgrowth
extending less than 6 mm. Neuromas were found at both
ends of the all six autografts in the Autograft Group at 4
weeks postoperatively. No neuroma was found at the
suture in the Fiber Group. Regenerated unmyelinated
axons were found, but no regenerated myelinated axon was
found at the distal end of the graft—1 mm proximal to the
distal suture threads—in both the Autograft Group and the
160
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
Fig. 2. Electron micrographs at the distal end of the nerve autograft and collagen nerve guide. Cross sections at the distal end of the autograft (a) and
collagen-filament nerve guide (b) at 8 weeks postoperatively. Arrow heads indicate myelinated axons and arrows indicate the residues of collagen
filaments. (Original magnification31000, scale bar: 10 mm.)
S. Yoshii, M. Oka / Brain Research 888 (2001) 158 – 162
Fiber Group at 4 weeks postoperatively. The distal ends of
the regenerated myelinated axons were found at 10–14
mm distal to the proximal suture threads in the Autograft
Group at 4 weeks postoperatively. The distal ends of the
regenerated myelinated axons were found at 12–16 mm
distal to the proximal suture threads in the Fiber Group.
The distal ends of the regenerated myelinated axons were
found at 2–4 mm distal to the proximal suture threads in
the Tube Group. Under the electron microscope, many
macrophages were found around the collagen material to
phagocytose it in the Fiber Group and the Tube Group at 4
weeks postoperatively.
The dissected nerve guides in the Fiber Group were
white-colored at 8 weeks postoperatively and their mean
diameter was 1.8 mm, which was larger than that of the
grafted tibial division of the sciatic nerve (1.1 mm) in the
Autograft Group. No neuroma was found at the suture in
the Autograft and Fiber Groups at 8 weeks postoperatively.
The collagen tubes were not found in all three rats and a
very thin white structure linked the nerve stumps in the
Tube Group. Regenerated myelinated and unmyelinated
axons were found at the distal end of the graft—1 mm
proximal to the distal suture threads—in both the Autograft
Group and the Fiber Group at 8 weeks postoperatively
(Fig. 2a,b). The mean number of myelinated axons was
approximately 4800 (48376604) in the distal end of the
nerve autograft (Autograft Group, six rats) at 8 weeks
postoperatively; while in the distal end of the collagenfilaments nerve guide (Fiber Group, six rats) it was
approximately 5500 (54916617). There were no statistically significant differences between groups (Wilcoxon’s
tests, P50.05). The mean fiber diameter was 3.3 mm in the
distal end of the nerve autograft at 8 weeks postoperatively; while in the distal end of the nerve guide it was 2.3
mm. The mean fiber diameter was significantly larger in
the Autograft Group (Student’s t-test, P50.05). No myelinated and unmyelinated axon was found in the thin white
structure in the Tube Group. Small residues of collagen
filaments were found among regenerated axons in the Fiber
Group (Fig. 2b). Few macrophages were found around the
collagen filaments.
The SFI values decreased after the nerve transection and
repair. The mean SFI values for the rats in the Autograft
Group was 2106.4 at 4 weeks postoperatively. The value
was 2121.5 in the Fiber Group. The value was 2117.2 in
the Tube Group. The values did not increase in all groups
at 8 weeks postoperatively. The values increased slightly
in all groups at 12 weeks postoperatively. The mean SFI
values for the rats in the Autograft Group was 271.0 at 12
weeks postoperatively. The value was 284.2 in the Fiber
Group. The value was 2105.8 in the Tube Group. The
three groups were considered to be not different practically
in SFI values. Toe contracture was not found in all groups
through the experimental period.
No interpretable compound action potential was recorded in all groups at 4 and 8 weeks postoperatively. No
161
EMG was recorded from the short muscles of the foot in
all groups at 4 and 8 weeks postoperatively. Interpretable
compound action potentials were recorded for two out of
three rats in the Autograft Group and two out of three rats
in the Fiber Group at 12 weeks postoperatively. The mean
nerve conduction velocity was 51.7 m / s for the Autograft
Group and 40.0 m / s for the Fiber Group. In all six rats
from the Autograft and Fiber Groups, good EMG was
recorded from the short flexor muscles of the foot when
the nerve was stimulated proximal or distal to the repair
site. No interpretable compound action potential or no
EMG from the short muscles of the foot was recorded in
the Tube Group at 12 weeks postoperatively.
Myelinated axons of the rat sciatic nerve had regenerated 20 mm along collagen-filaments without a tube or
neurotrophic additives by 8 weeks postoperatively in this
study. It has been reported that increased permeability
improves axonal regeneration [11–13,16]. Yoshii et al.
reported that they had obtained good regeneration of axons
using a nerve guide which was made of laminin-coated
filaments, instead of a tube [26]. A nerve guide made of
filaments without a tube has high permeability. In our
study, the number of myelinated axons of the tibial
division of the normal sciatic nerve was smaller than the
previously reported one [23]. This may be due to differences in staining and counting methods. The number of
regenerated myelinated axons in the collagen-filaments
nerve guide was not smaller than the number of regenerated myelinated axons in the nerve autograft. The mean
fiber diameter and mean nerve conduction velocity were
significantly less in the collagen-filaments nerve guide
group than those in the Autograft Group at 8 weeks
postoperatively. A study with an extended period should
be made to investigate these findings. The collagen filaments were considered easy to resorb because only small
residues of collagen filaments were found among regenerated axons at 8 weeks postoperatively (Fig. 2b).
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