Recovery of peripheral nerve with massive loss defect by tissue engineered guiding regenerative gel

Abstract

Objective: Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated.

Background: Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft "gold standard" treatment.

Figure 1

(a) Creating 15 mm segmental loss nerve damage; (b) nerve reconstruction using 17 mm tube; (c) nerve reconstruction using 15 mm autologous nerve graft.

Figure 2

(a) No axons, connective scar tissue; (b) massive growth of regenerative axons into the tube. The graph reflects histological score of the distal part of the nerve (blind examination) in difference between amounts of axons in the GRG group (good amount of axons with tendency to large-diameter axons) versus empty tube (scar tissue—no axons).

Figure 3

(a) Regenerated small axons in the HA treated group. (b) Regenerated axons in the GRG treated group (increased quality and quantity). The graph reflects histological score of the distal part of the nerve (blind examination) in difference between amounts of axons in the GRG group (good amount of axons with tendency to large-diameter axons) versus HA group (mild to moderate amount of axons).

Figure 4

GRG gel is shown to enable nerve regeneration similar to autologous nerve graft reconstruction (gold standard). The graph reflects histological score of the distal part of the nerve (blind examination) in difference between amounts of axons in the GRG group (good amount of axons with tendency to large-diameter axons) versus autologous nerve graft group (good amount of axons).