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.

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.