Neuroma formation after amputation as a long‐term deficiency leads to spontaneous neuropathic pain that reduces quality of life of patients. To prevent neuroma formation, capping techniques are implemented as effective treatments. However, an ideal, biocompatible material covering the nerves is an unmet clinical need. In this study, biocompatible characteristics presented by the poly(D,L‐lactic acid)/arginylglycylaspartic acid (RGD peptide) modification of poly{(lactic acid)‐co‐ [(glycolic acid)‐alt‐(L‐lysine)]} (PRGD/PDLLA) are evaluated as a nerve conduit. After being capped on the rat sciatic nerve stump in vivo, rodent behaviors and tissue structures are compared via autotomy scoring and histological analyses. The PRGD/PDLLA capped group gains lower autotomy score and improves the recovery, where inflammatory infiltrations and excessive collagen deposition are defeated. Transmission electron microscopy images of the regeneration of myelin sheath in both groups show that abnormal myelination is only present in the uncapped rats. Changes in related genes (MPZ, MBP, MAG, and Krox20) are monitored quantitative real‐time polymerase chain reaction (qRT‐PCR) for mechanism investigation. The PRGD/PDLLA capping conduits not only act as physical barriers to inhibit the invasion of inflammatory infiltration in the scar tissue but also provide a suitable microenvironment for promoting nerve repairing and avoiding neuroma formation during nerve recovery.

BackgroundNerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration.MethodsIn the present study, poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PLGL) was modified by grafting Gly-Arg-Gly-Asp-Gly (RGD peptide) and nerve growth factor (NGF) for fabricating new PLGL-RGD-NGF nerve conduits to promote nerve regeneration and functional recovery. PLGL-RGD-NGF nerve conduits were tested in the rat sciatic nerve transection model. Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by footprint analysis, electrophysiology, and histologic assessment. Experimental data were processed using the statistical software SPSS 10.0.ResultsThe sciatic function index value of groups PLGL-RGD-NGF and autograft was significantly higher than those of groups PLGL-RGD and PLGL. The nerve conduction velocities of groups PLGL-RGD-NGF and autograft were significantly faster than those of groups PLGL-RGD and PLGL. The regenerated nerves of groups PLGL-RGD-NGF and autograft were more mature than those of groups PLGL-RGD and PLGL. There was no significant difference between groups PLGL-RGD-NGF and autograft.ConclusionsPLGL-RGD-NGF nerve conduits are more effective in regenerating nerves than both PLGL-RGD nerve conduits and PLGL nerve conduits. The effect is as good as that of an autograft. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair.

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A novel nerve guidance conduit comprising poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} (PRGD), poly (d,l-lactic acid) (PDLLA) and β-tricalcium phosphate (β-TCP) was constructed to facilitate the peripheral nerve regeneration. From the comparative study, PDLLA/PRGD/β-TCP conduit achieved the best recovery in regard of the ultrastructure observation and the SFI evaluation. At the first stage of the injury (7 days), the maximum expression augments in ZnSOD (6.4 folds) and GPX4 (6.8 folds) were observed in PDLLA/PRGD/β-TCP group; while striking rise in actin (6.8 folds), tubulin (5.6 folds), and ERM components expressions were observed later (35 days). Meanwhile, compared with PDLLA and PDLLA/PRGD conduits, PDLLA/PRGD/β-TCP conduits achieved the highest local nerve growth factor (NGF) content and an accumulating BDNF content. We speculated that addition of RGD and β-TCP in the composites were the main positive factors to build the microenvironment rich in NGF and BDNF, which help to counteract with the oxidative stress and to boost the cytoskeletal protein expressions. Therefore, PDLLA/PRGD/β-TCP could be promising composites used in peripheral nerve regeneration.

A new polymer poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (poly[LA-co-(Glc-alt-Lys)]) was synthesized and modified with a cell adhesion peptide, Gly-Arg-Gly-Asp-Tyr (GRGDY, abbreviated as RGD). The process for preparing poly[LA-co-(Glc-alt-Lys)]/RGD involved four steps: Firstly, (3S)-3-[4-(benzyloxycarbonylamino)butyl]morpholine-2,5-dione (BMD) was synthesized by bromoacetyl bromide and N ε -(benzyloxycarbonyl)-L-lysine [L-Lys(Z)]. Secondly, poly{(lactic acid)-co-[(glycolic acid)-alt-(N ε -benzyloxycarbonyl-L-lysine)]} (poly{LA-co-[Glc-alt-Lys(z)]}) was obtained by copolymerization of D,L-lactide and BMD. Then, poly[LA-co-(Glc-alt-Lys)] was synthesized by catalytic hydrogenation of poly{LA-co-[Glc-alt-Lys(z)]}. Finally, poly[LA-co-(Glc-alt-Lys)] was modified with RGD peptide in the presence of 1,1-carbonyldiimidazole (CDI). The structures of poly[LA-co-(Glc-alt-Lys)]/RGD and its precursors were characterized by FT-IR, 1 H NMR, 13 C NMR, MS, gel permeation chromatography (GPC), amino acid analysis(AAA). RSC96 cells were used to evaluate the cell affinity of the poly[LAco-(Glc-alt-Lys)]/RGD films and poly(D,L-lactide) (PDLLA ) films. The results of cell culture showed that poly[LA-co-(Glc-alt-Lys)]/RGD was more beneficial to cell adherence and growth than PDLLA.