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, 10 (9), 1491-7

Polylactic-co-glycolic Acid Microspheres Containing Three Neurotrophic Factors Promote Sciatic Nerve Repair After Injury

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Polylactic-co-glycolic Acid Microspheres Containing Three Neurotrophic Factors Promote Sciatic Nerve Repair After Injury

Qun Zhao et al. Neural Regen Res.

Abstract

A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

Keywords: biological compatibility; brain-derived neurotrophic factor; microspheres; nerve growth factor; nerve injury; nerve regeneration; nerve repair; neurotrophin-3; polylactic-co-glycolic acid copolymer.

Conflict of interest statement

Conflicts of interest: None declared.

Figures

Figure 1
Figure 1
Polylactic-co-glycolic acid (PLGA) microsphere image (A) and implantation of sustained-release microspheres into the injured sciatic nerve (B). (A) PLGA microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factors were produced with the multiple emulsion-solvent evaporation method, at 300-μm diameter. (B) After the left sciatic nerve mutilation injury occurred, end-to-end anastomosis was performed under the microscope, and PLGA microspheres were implanted into the damaged sciatic nerve.
Figure 2
Figure 2
Effect of composite microsphere transplantation on histological change of rat sciatic nerve (hematoxylin-eosin staining, light microscope, × 400). At 6 weeks postoperatively, sciatic nerve fibers grew to varying degrees in the experimental and control groups, but the density, diameter and quantity showed significant differences between the two groups. (A) Nerve fibers in the experimental group were dense and abundant, and distributed uniformly, newborn blood capillary and thick myelin sheath (arrows) were clearly visible. (B) The quantity of nerve fibers in the control group was significantly less than in the experimental group, nerve fibers distributed unevenly and myelin sheaths (arrows) were thinner.
Figure 3
Figure 3
In vitro release curves of various neurotrophic factors over 60 days following implantation of microspheres. The release amount of various neurotrophic factors peaked at 10–15 days, maintained a stable level at 30 days, and decreased after 45 days, but the release was still detected at 60 days. NGF: Nerve growth factor; NT-3: neurotrophin-3; BDNF: brain-derived neurotrophic factor.

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