Types of neural guides and using nanotechnology for peripheral nerve reconstruction

Abstract

Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed.

Keywords: nanofibers; nerve reconstruction; neural guide; peripheral nerve injuries.

Figure 1

Cross-sectional anatomy of a peripheral nerve. Inset at left shows an unmyelinated fiber. Inset at bottom shows a myelinated fiber.

Figure 2

Tubes or guide types for peripheral nervous system regeneration.

Figure 3

Silicone tube for nerve regeneration.

Figure 4

Polyhydroxybutyrate conduit preparation. A) Polyhydroxybutyrate material is manufactured as a sheet that can be cut to measure of any size. B) Polyhydroxybutyrate sheet is rolled around a 16 gauge needle. C) Heat sealing of the rolled conduit. D) Rolled and sterilized conduits ready to be implanted. E) Implanted polyhydroxybutyrate conduit at the sciatic nerve site. F) Implanted polyhydroxybutyrate strip at the sciatic nerve site.

Figure 5

Representative photomicrograph of braided chitosan hollow tubes made from chitosan yarns through an industrial braiding technique.

Figure 6

Electron micrograph of a poly glycolic acid (PGA)-collagen composite nerve conduit filled with collagen sponge. The PGA-collagen composite conduit is filled with a three-dimensional sponge matrix.

Figure 7

Ultrastructure of alginate-based anisotropic capillary gels (ACH). A) Illustration of the different phases of anisotropic capillary gel formation. B) Macroscopic appearance of ACH bodies. C) ACH in cross- and D) longitudinal sections. Scale: B 1 cm, C 100 mm, and D 100 mm.

Figure 8

A, B) Schwann cells on a smooth compression-molded poly-D,L-lactic acid substrate biomaterials. C) Oriented Schwann cell growth on micropatterned biodegradable polymer substrates.

Figure 9

A schematic of axon stretch-growth. A) Neurons are plated on two adjoining substrates and are given sufficient time for axons to bridge the two substrates and integrate with neurons on both sides. B) The stretching frame displaces one population of neurons away from the other, thereby elongating the interconnecting axons. C) Axon stretch-growth is a process that can be gradually induced to achieve a rate of 1 cm/day of growth and to lengths of at least 10 cm.

Figure 10

Immunocytochemical analysis of axon stretch-growth. A and B Antibodies against tau and MAP2 were utilized to determine that elongating processes were axons. A) The entire length of stretch-growing axons labeled positive for tau protein. B) MAP2 was labeled within the cell bodies and was void along elongating processes indicating that these processes are axons. C–E) Confocal microscopic images of axons elongated to 5 cm in length. Antibodies against (C)—tubulin (SMI-61), (D) 200 kDa phosphorylated neurofilament (SMI-31), and (E) tau strongly labeled axons along their entire 5 cm of length. Scale bars: (B) 50 m; (E).

Figure 11

Selected approaches for oriented scaffolds/matrices for peripheral nerve repair. Magnetically aligned structures have so far been demonstrated with collagen. Scanning electron micrographs of collagen with and without 8-T magnetic field exposure for two hours. The diameter of collagen fibril is about 100 nm. A) Control group. B) Exposed group. Scale bars: 5 mm. Light micrographs of Schwann cells cultured for 60 hours with and without 8-T magnetic field exposure. A) Control group. B) Exposed group. Scale bars: 100 mm.

Figure 12

Experimental model. Scanning electron microscopy images of the electrospun poly-D,L-lactic acid/polycaprolactone nerve guide conduit (A) and magnified details of the tube wall (B) microfibers and nanofibers range in diameter from approximately 280 nm to 8 μm. The nonwoven fibrous microstructure is characterized by small pores (700 nm) and large pores (20 μm). C) Micrograph of sham-operated rat sciatic nerve (experimental Group 1). D) Micrograph of prosthesis implanted, filled with saline solution, and sutured to the transected nerve (experimental Group 3).

Figure 13

Longitudinal sections of nerve regenerated within the implanted guide channel. In the conduit, the regenerated nerve bridged the 10 mm gap, reconnecting the two sciatic nerve stumps. (A) Four months after surgery, hematoxilyn and eosin staining shows the presence of regenerated tissue filling the conduit lumen; decreased lumen diameter is observable at middle length of the guidance channel. Regenerated tissue positive to Bielschowsky staining (B) and to anti-β-tubulin antibody (C) shows nervous projections oriented along the major axis of the prosthesis bridging the 10 mm gap between the severed sciatic nerve stumps (image sequence collected at 4 × magnification).