Nerve gap repair using Schwann cell-seeded artificial grafts

Problem:
For the past seven years we have been investigating semi-synthetic alternatives to nerve autografts for repair of gaps resulting from injury, supported by a series of VA Rehabilitation R&D Merit Review grants. Autografts are limited by the amount of donor nerve that a patient can sacrifice to reconstruct more essential nerves.

Approach:
Our graft essentially consists of Type I collagen matrix combined with cultured Schwann cells inserted into a biodegradable conduit. Although others have tested collagen matrices, our method reproduces the geometry of linear channels present in a nerve autograft, and in animal experiments has shown the same functional recovery as an autograft.

Based on this result, a a 3-year clinical trial was begun in October, 1996, with Vincent R. Hentz, MD, Chief of Hand Surgery, as co-principal investigator; up to 10 patients per year requiring nerve repair in the hand will be enrolled starting in April, 1998.

Related Work:
We are considering use of the graft in repair of facial nerves, to assist Dr. David Terris, Stanford Div. of Otolaryngology. We are also collaborating with Talat Khan, PhD, at Hines VA Rehabilitation R&D Center, Chicago, by making Schwann cell-seeded implants for spinal cord injuries in rats.

Investigators:

• Eric E. Sabelman, PhD
• Vincent R. Hentz, MD, Chief of Hand Surgery (Clinical Trials)

Collaborators:

• Dr. David Terris, Stanford Division of Otolaryngology (use of the graft in repair of facial nerves and student projects)
• Talat Khan, PhD, Hines VA Rehabilitation R&D Center, Chicago (Schwann cell-seeded implants for spinal cord injuries in rats)

Findings from a 1994 experiment in which grafts containing oriented collagen core matrix with ("STR+SC") or without ("STR") rat Schwann cells were implanted into rat peroneal nerves; controls were sutured autografts ("SAG") and sham operations. Exposure of the nerve alone caused inflammatory response and some functional loss. Autografts and Schwann-cell seeded grafts recovered >90% of function after 3 months. Without Schwann cells, recovery averaged 70% in the same period.

The bar graphs show group means of cross-sectional histology. There were higher numbers of myelinated axons distal to the implant in SAG and sham groups, including multiple branches as occur during the healing process. Area occupied by axons was also lower in both STR groups, a somewhat misleading measure, since most of the collagen core is still intact and displaces axons. The conclusion is that the high surface area of the core and the Schwann cell population promote rapid elongation and maturation (i.e.: elimination of excess branches) of axons through the implant to their target muscle or sensory connections (illustrated by the microphotograph of a core element with immunostained axons from an in vitro experiment).

Last updated March 26, 1999