Using an established rat peripheral nerve regeneration model, we investigated the role of glial growth factor (GGF) in nerve regeneration in combination with a novel bioresorbable poly(lactic-co-glycolic) acid (PLGA) guide in vivo. Schwann cells, established from a 1-cm segment of excised rat sciatic nerve, were isolated and seeded onto nerve guides with or without GGF (n = 24/group). Living nerve guides were re-established in these animals, and nerve regeneration was assessed over a period of 12 weeks. Histological studies revealed a reduction in the total axon count and the number of myelinated axons in the presence of exogenously added Schwann cells compared to saline controls. In contrast, the addition of GGF alone enhanced the total number of axons and significantly increased the number of blood vessels. Although combining GGF with Schwann cells negated the enhanced numbers of axons and blood vessels seen with GGF alone, this combination resulted in the highest myelination index and the fastest conduction velocities recorded. The PLGA guide material did not trigger any histologically detectable host response and was permissive for nerve regeneration in this animal model. The results from this study demonstrate the potential utility of this guide in vivo and establish a promotional role for GGF in nerve regeneration.

Vein grafts have been used both experimentally and clinically to bridge gaps in peripheral nerves. This study describes a modification of the vein graft technique in which vein graft conduits are pulled inside-out before anastomosis with proximal and distal nerve stumps. This technique creates an autogenous vein conduit with the collagen-rich adventitial surface exposed to the regenerating axons. The inside-out technique is a fast and simple modification of the standard vein graft technique and produces an accelerated rate of nerve regeneration and significantly earlier myelination compared with the results obtained from the use of polyethylene nerve guides and standard vein graft conduits.

Hyaluronic acid has been shown to enhance peripheral nerve regeneration in vitro. It has been proposed that, during the fibrin matrix phase of regeneration, hyaluronic acid organizes the extracellular matrix into a hydrated open lattice, thereby facilitating migration of the regenerating axons. Hyaluronic acid solutions and saline control solutions were injected into a nerve guide spanning a transected gap in the sciatic nerve of Sprague-Dawley rats (five in each group). Nerve conduction velocities were measured at 4 weeks by electromyography (EMG) before sacrifice of the animals. These studies demonstrated increased conduction velocities in the hyaluronic acid group compared with control animals (P = 0.006). After the animals were sacrificed, regenerated axon cables were quantified histologically, and axon branching was delineated by retrograde tracer analysis. In addition, the hyaluronic acid group showed an increase in myelinated axon counts at 4 weeks (P= 0.03). An increase in retrograde flow was demonstrated in the hyaluronic acid groups compared with animals receiving saline solution.

The inside-out vein graft is a vein conduit pulled through itself to invert the normal orientation and place the adventitial layer within the lumen of the conduit. Our study compares regeneration of peripheral nerves in the rat through two conduits: inside-out graft of the jugular vein and autogenous nerve graft. In 10 rats, the right jugular vein was harvested, turned inside out, and used to bridge a 10 mm defect created in the right sciatic nerve. The 10 mm nerve segment from the right was then used as a standard nerve graft to bridge a 10 mm gap created in the left sciatic nerve. Rats were sacrificed at 8 and 12 weeks. Regeneration on the inside-out vein graft side showed superior functional results (faster conduction velocities) and improved histological results (greater axon counts) compared with the nerve grafted side. We feel the adventitial surface of the wall of the vein promotes nerve regeneration by providing an environment rich with collagen, laminin, and Schwann cells and promotes increased vascularization of the new nerve.

Schwann cells appear to stimulate the early phases of axon regeneration. The reported study investigated whether nerve guides with Schwann-cell monolayers can help regenerating nerves span gaps larger than 1 cm. Schwann-cell cultures were established by resecting 1-cm segments of sciatic nerves of adult female Sprague-Dawley rats, establishing cell monolayers in 24-mm nerve guides, and then reinserting these "living guides" into 20-mm nerve gaps of the rats from which they were developed. Control groups had plain guides (no Schwann cells) inserted between the same 20-mm gaps. In the experimental group, resected nerves regrew progressively. At 8 weeks, regrowth had spanned the entire gap in 60 percent of the animals. Axon counts increased at each successive time point. Regeneration did begin to occur in the control group but by 8 weeks, those cables had atrophied. The experimental groups displayed more central connections and higher nerve conduction velocity. Explant organ cultures of rat sciatic nerve can be used to develop nonneural conduits with Schwann-cell monolayers. These living artificial nerve guides permit the spanning of gaps of at least 20 mm.