Recent advances in biomaterials have resulted in the emergence of tubulation repair as a clinically viable alternative to autograft repair of peripheral nerve injuries. Tubes composed of a number of synthetic and natural materials have been shown capable of promoting regeneration across short nerve gaps. Previous research in our laboratory has demonstrated that a collagen conduit filled with a porous collagen-glycosaminoglycan matrix is capable of promoting axon regeneration equivalent to that promoted by a nerve autograft across a 10-mm gap in the rat sciatic nerve. The purpose of the present study was to determine the maximum gap length across which axon regeneration would occur when the gap was bridged with either a silicone tube or a matrix-filled collagen conduit.

In order to obtain gap lengths in excess of 15 mm in the rat sciatic nerve, a cross-anastomosis technique was used in which the proximal stump of the left nerve was bridged by the tubular implant to the distal right nerve. Groups of animals with nerve gaps between 4 and 22 mm in length were implanted with either a silicone tube or with a matrix-filled collagen conduit. Regeneration was evaluated after 9 and 12 weeks by determining the percentage of animals for each gap length in which axons had reached the gap midpoint and by histological quantification of myelinated axons at the gap midpoint and in the distal nerve.

After 12 weeks, the silicone tube implant yielded comparatively poor regeneration, with no animals exhibiting axon regeneration across gap lengths greater than 10 mm and only a portion of animals exhibiting regeneration across gap lengths between 6 and 10 mm. In contrast, after 12 weeks the matrix-filled collagen conduit promoted regeneration in nearly all animals in each gap length group up to and including 22 mm. Results from axon counting indicated that at 9 weeks, a substantial number of myelinated axons had regenerated to the midpoint of the matrix-filled collagen conduit in shorter gap lengths (3123±890 axons for 12-mm gap) while only few axons had reached the midpoint of larger gaps (79±39 for 20-mm gap). The number of myelinated axons had increased by 12 weeks (3184±773 for 16-mm gap and 356±110 for 22-mm gap).

These data demonstrate that the matrix-filled collagen conduit was capable of promoting axon regeneration across gap lengths up to 22 mm, and it is likely that regeneration would be possible across gap lengths in excess of 22 mm.