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A novel artificial nerve graft for repairing long-distance sciatic nerve defects: a self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit.

Wang X, Pan M, Wen J, Tang Y, Hamilton AD, Li Y, Qian C, Liu Z, Wu W, Guo J - Neural Regen Res (2014)

Bottom Line: In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat.Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit.Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong Province, China.

ABSTRACT
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

No MeSH data available.


Related in: MedlinePlus

Immunofluorescence staining and transmission electron microscopy (TEM) showing the remyelination of regenerated axons in the nerve conduits.(A–C) MBP (green) and NF200 (red) double immunostaining showing significant remyelination of regenerated axons in the middle part of the PN (A) and SPC (B) grafts, but limited remyelination in the EPC graft (C). a–c are magnified images of the boxed areas in A–C. (D–G) TEM showing the presence of typical remyelinated fibers in all implant types (E, PN group; F, SPC group; G, EPC group), although the diameter of the fibers and the thickness of the myelin were less than in the naive nerve (D). (H–K) Quantification showing the remyelination rate of axons (H), axon diameter (I), myelin thickness (J) and G-ratio (K) of the myelinated fibers in the various groups. The data are expressed as the mean ± SD. One-way analysis of variance followed by Bonferroni post hoc comparison was used to analyze intergroup differences. *P < 0.05, N.DP > 0.05. PN: Syngeneic peripheral nerve; SPC: self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit; EPC: empty poly(lactic-co-glycolic acid) conduit.
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Figure 4: Immunofluorescence staining and transmission electron microscopy (TEM) showing the remyelination of regenerated axons in the nerve conduits.(A–C) MBP (green) and NF200 (red) double immunostaining showing significant remyelination of regenerated axons in the middle part of the PN (A) and SPC (B) grafts, but limited remyelination in the EPC graft (C). a–c are magnified images of the boxed areas in A–C. (D–G) TEM showing the presence of typical remyelinated fibers in all implant types (E, PN group; F, SPC group; G, EPC group), although the diameter of the fibers and the thickness of the myelin were less than in the naive nerve (D). (H–K) Quantification showing the remyelination rate of axons (H), axon diameter (I), myelin thickness (J) and G-ratio (K) of the myelinated fibers in the various groups. The data are expressed as the mean ± SD. One-way analysis of variance followed by Bonferroni post hoc comparison was used to analyze intergroup differences. *P < 0.05, N.DP > 0.05. PN: Syngeneic peripheral nerve; SPC: self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit; EPC: empty poly(lactic-co-glycolic acid) conduit.

Mentions: Double staining with NF200 and MBP antibodies showed that many NF200-positive axons in the implant were wrapped with MBP-positive myelin (Figure 4A–C). To better evaluate regeneration efficiency and remyelination, we examined ultrathin transverse sections of the middle segment of the implants with transmission electron microscopy. The regenerated axons and myelin in the PN and SPC groups were smaller than in the naive sciatic nerve, but the regenerated axons almost completely filled the implants, and many of these were myelinated (Figure 4D–F). In the EPC grafts, the regenerated axons were scattered mainly around the edges of the conduit (Figure 4G). Quantification demonstrated that the remyelination rate of axons was significantly higher in the SPC group than in the EPC group (P < 0.05), but was lower than in the naive and PN groups (P < 0.05) (Figure 4H). There was no statistically significant difference in axon diameter or myelin thickness between the SPC and EPC groups. However, axon diameter and myelin thickness in the SPC and EPC groups were significantly less than in the naive and PN groups (P < 0.05) (Figure 4I, J). Additionally, the G-ratio of myelinated fibers was lowest in the naive group, and highest in the EPC group; however, no statistically significant difference was detected among the groups (P > 0.05) (Figure 4K).


A novel artificial nerve graft for repairing long-distance sciatic nerve defects: a self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit.

Wang X, Pan M, Wen J, Tang Y, Hamilton AD, Li Y, Qian C, Liu Z, Wu W, Guo J - Neural Regen Res (2014)

Immunofluorescence staining and transmission electron microscopy (TEM) showing the remyelination of regenerated axons in the nerve conduits.(A–C) MBP (green) and NF200 (red) double immunostaining showing significant remyelination of regenerated axons in the middle part of the PN (A) and SPC (B) grafts, but limited remyelination in the EPC graft (C). a–c are magnified images of the boxed areas in A–C. (D–G) TEM showing the presence of typical remyelinated fibers in all implant types (E, PN group; F, SPC group; G, EPC group), although the diameter of the fibers and the thickness of the myelin were less than in the naive nerve (D). (H–K) Quantification showing the remyelination rate of axons (H), axon diameter (I), myelin thickness (J) and G-ratio (K) of the myelinated fibers in the various groups. The data are expressed as the mean ± SD. One-way analysis of variance followed by Bonferroni post hoc comparison was used to analyze intergroup differences. *P < 0.05, N.DP > 0.05. PN: Syngeneic peripheral nerve; SPC: self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit; EPC: empty poly(lactic-co-glycolic acid) conduit.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: Immunofluorescence staining and transmission electron microscopy (TEM) showing the remyelination of regenerated axons in the nerve conduits.(A–C) MBP (green) and NF200 (red) double immunostaining showing significant remyelination of regenerated axons in the middle part of the PN (A) and SPC (B) grafts, but limited remyelination in the EPC graft (C). a–c are magnified images of the boxed areas in A–C. (D–G) TEM showing the presence of typical remyelinated fibers in all implant types (E, PN group; F, SPC group; G, EPC group), although the diameter of the fibers and the thickness of the myelin were less than in the naive nerve (D). (H–K) Quantification showing the remyelination rate of axons (H), axon diameter (I), myelin thickness (J) and G-ratio (K) of the myelinated fibers in the various groups. The data are expressed as the mean ± SD. One-way analysis of variance followed by Bonferroni post hoc comparison was used to analyze intergroup differences. *P < 0.05, N.DP > 0.05. PN: Syngeneic peripheral nerve; SPC: self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit; EPC: empty poly(lactic-co-glycolic acid) conduit.
Mentions: Double staining with NF200 and MBP antibodies showed that many NF200-positive axons in the implant were wrapped with MBP-positive myelin (Figure 4A–C). To better evaluate regeneration efficiency and remyelination, we examined ultrathin transverse sections of the middle segment of the implants with transmission electron microscopy. The regenerated axons and myelin in the PN and SPC groups were smaller than in the naive sciatic nerve, but the regenerated axons almost completely filled the implants, and many of these were myelinated (Figure 4D–F). In the EPC grafts, the regenerated axons were scattered mainly around the edges of the conduit (Figure 4G). Quantification demonstrated that the remyelination rate of axons was significantly higher in the SPC group than in the EPC group (P < 0.05), but was lower than in the naive and PN groups (P < 0.05) (Figure 4H). There was no statistically significant difference in axon diameter or myelin thickness between the SPC and EPC groups. However, axon diameter and myelin thickness in the SPC and EPC groups were significantly less than in the naive and PN groups (P < 0.05) (Figure 4I, J). Additionally, the G-ratio of myelinated fibers was lowest in the naive group, and highest in the EPC group; however, no statistically significant difference was detected among the groups (P > 0.05) (Figure 4K).

Bottom Line: In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat.Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit.Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong Province, China.

ABSTRACT
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

No MeSH data available.


Related in: MedlinePlus