Regeneration across preserved peripheral nerve grafts

Abstract

The potential to store nerve grafts for a prolonged period of time was assessed in a rat sciatic nerve model. Three-centimeter syngeneic nerve grafts were stored in Belzer/University of Wisconsin cold storage solution at different temperatures (5 degrees C, 22 degrees C, or 37 degrees C) for varying time periods (6 h, 24 h, or 3 weeks) prior to transplantation. Functional assessment using serial walking track analyses revealed no difference between storage times and temperatures. At 14 months postengraftment, the conduction velocities and the number of myelinated fibers that had regenerated across all grafts stored at 5 degrees C for all time periods tested were superior to grafts stored at either 22 degrees C or 37 degrees C. Nerve grafts stored for up to 3 weeks at 5 degrees C acted as effective conduits for proximal regenerating fibers and resulted in histologic, electrophysiologic, and functional results equivalent to fresh nerve grafts. Nerve graft storage may be applicable to nerve allografts and potentially provide allograft material that requires reduced or no associated host immunosuppression.

Cold preserved nerve allografts: Changes in basement membrane, viability, immunogenicity, and regeneration

“…Recently, we assessed short-term graft storage in an autograft model and found that regeneration and function across autografts stored at 5°C for 21 days was equivalent to fresh autografts. 16,17 Nerve allograft pretreatment by repeated cycles of deep freezing and thawing to render grafts acellular was first described by Sanders in 1954 61 and is of current interest. 12,18,25,28,33,54,55,65,67 Freeze-thawing was found to prevent effectively the lymphocyte infiltrate seen in fresh allografts and allow regeneration similar to autografts.…”

Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

“…Previous studies have tried using UWS for nerve graft preservation in peripheral nerve allotransplantation (Levi et al, 1994;Evans et al, 1995). However, it has been found that while short storage intervals of less than one week in UWS alone resulted in peripheral nerve segments containing functioning SCs, the long-term preservation of peripheral nerve segments for more than three weeks caused a substantial loss of SCs (Levi et al, 1994).…”

“…Most pretreatment methods, such as chemical treatment, irradiation, freezing, lyophilization, and freezethawing could effectively reduce nerve graft antigenicity; however, nerve regeneration remains inferior to autografts. One problem has been acellularizing the graft (Song, Yang, Russell, 2009), and although short nerve deficits (less than 3 cm) can be bridged by acellular grafts, longer deficits may be more dependent upon the presence of donor-derived viable SCs (Hems, Glasby, 1992;Evans et al, 1995;Strauch et al, 1996;Song, Yang, Russell, 2009), because viable SCs are essential for successful axonal regeneration through longer deficits (Hall, 1986;Feneley, Fawcett, Keynes, 1991;Bunge, 1993). Furthermore, Blais, Grenier, Berthod and Sun et al found that tissueengineered skin or acellular nerve allografts seeded with SCs could improve nerve regeneration (Blais, Grenier, Berthod, 2009;Sun et al, 2009).…”

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

“…Although natural materials are ideal, there are some inherent difficulties and these include undesirable immune responses, the potential use of immunosuppressive drugs, and batch to batch variation (Hudson et al, 1999). In an attempt to use natural material, nerve grafts have been stored for prolonged periods of time (Evans et al, 1995). However, it appear as the degeneration interval increased, the regenerative supporting ability of the stored nerve is compromised (Gulati, 1996).…”