Hyaluronic acid through a new injectable nerve guide delivery system enhances peripheral nerve regeneration in the rat

Abstract

The use of non-neural conduits to bridge gaps in peripheral nerves has been noted in the literature for many years. A logical extension of this concept is the introduction of neurotrophic or growth promoting factors into the lumen. We present here an injectable nerve guide that allows percutaneous access to the microenvironment of the regenerating peripheral nerve within the guide's lumen. Hyaluronic acid, a compound associated with decreased scarring and improved fibrin matrix formation, is added sequentially to the regenerating peripheral rat sciatic nerve via this injectable nerve guide. Assessment of nerve regeneration and reinnervation shows better conduction velocity, higher axon counts, and a trend toward earlier myelination with hyaluronic acid compared with saline. This work not only implies hyaluronic acid's role as an agent that aids nerve growth but also describes a new tool that allows percutaneous access to the milieu of a regenerating nerve.

Hyaluronic acid enhances peripheral nerve regeneration in vivo

“…Although not directly tested here, a proposed mechanism for the enhancement of nerve regeneration we observed is that hyaluronic acid modifies this fibrin matrix into a porous, lubricated structure more accessible to ingrowing neurites. 3 Hyaluronic acid has been shown to influence the motility of growing cells by way of its cell surface interactions with extracellular matrix fibroblasts during a number of diverse biological processes. The mechanism for enhancement of peripheral nerve regeneration observed here may be analogous to the effect hyaluronic acid has on cells during neural development, embryogenesis, limb regeneration, and wound healing.…”

“…1,2 The absence of such a conduit permits ingrowth of fibrous scar tissue, which inhibits the migration of the reforming axon. 3 In the past decade, researchers [3][4][5] have reported on the use of different materials for fabricating nerve guides. Many investigators have enhanced the peripheral nerve regeneration process and prevented proximal degeneration by adding different substances to the lumen of a nerve guide chamber.…”

“…The injection ports, 3 manufactured by Dow Corning Corporation (Midland, MI), have a diameter of 14 mm, a height of 7.4 mm, and an internal volume of 0.05 ml. The nerve guide device is made by placing a 1.4-cm polyethylene nerve guide (Intramedic, Fisher Science, Springfield, NJ), with an inside diameter of 1.67 mm and outside diameter of 2.08 mm, between the tubing from two filling ports.…”

Enhanced Femoral Nerve Regeneration After Tubulization with a Tyrosine-Derived Polycarbonate Terpolymer: Effects of Protein Adsorption and Independence of Conduit Porosity

“…13 Nondegradable polyethylene (PE) has shown similar capabilities, but thus far only in animal models. [14][15][16] Whereas these conduits have provided an important benchmark for nerve regeneration, their inability to degrade can result in chronic host tissue response and/or nerve compression months after implantation, deterring regeneration. [17][18][19] To avoid these issues, biodegradable materials have been developed and utilized for the fabrication of nerve conduits.…”

Peripheral nerve injury: A review and approach to tissue engineered constructs

“…Alternatively, these molecules could be placed on natural biological conduits through adhesion molecules or similar process. Variable results have been demonstrated by the incorporation of these materials within conduits, however it appears that by reducing the concentration of protein gel or shorting the oligopeptide sequence, axonal proliferation can be promoted (Valentini et al, 1987;Williams et al, 1987;Madison et al, 1988;Archibald et al, 1991;Ballamkonda et al, 1995aBallamkonda et al, ,1995bSeckel et al, 1995;Yannas, 1995;Labrador et al, 1998). Components of the ECM and matrix analogues have also demonstrated promise in nerve replacement (Yannas, 1995).…”