Chaining Nerve Grafts With An Additional Suture Line Has Limited Impact On Axonal Regeneration
Ying Yan, MD, PhD; Amy M. Moore, MD;Daniel A. Hunter, RA; Xueping Ee, MD, MS; Susan E. Mackinnon, MD; Matthew D. Wood, PhD
Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO
Introduction: In cases of limited donor supply, the end-to-end coaptation of multiple nerve grafts (autograft or acellular nerve allografts-ANAs) to repair long nerve gaps has been performed. In this study, we sought to evaluate the effect of an added suture line on nerve regeneration and functional return when using either an autograft or ANA “chained” together.
Materials & Methods: Rat sciatic nerve was transected and repaired with 2cm nerve grafts. Nerve grafts consisted of either isografts (2cm: single, or a 1cm segment repaired to a 1cm segment: chained) or ANAs (single or chained). At an endpoint of 8 weeks post surgery, EDL muscle force and mass was measured, and nerve was harvested for quantitative histology (histomorphometry). In a separate parallel study, the same procedures and groups were employed, where nerves were harvested 2 weeks following graft implantation to assess gene expression changes using qRT-PCR. Collagen I, CD31, Ang-2, Jag1, VEGF and Dll4 expression levels at the middle of the grafts were determined.
Results: Contractile extensor digitorum longus (EDL) muscle force production was comparable between nerve isografts and ANAs as well as between single or chained groups. EDL muscle mass recovery was significantly increased by using a nerve isografts compared to ANAs, regardless of using a coapted nerve chains. Myelinated axon numbers assessed in nerve distal to the grafts were comparable between single and chained isografts and the single ANA, not the chained ANA.
Assessment of axonal regeneration within the grafts revealed stark differences. Myelinated axon numbers in the distal graft and proximal graft were similar between isografts groups (single or chained). However, ANAs, either single or chained, demonstrated decreased myelinated axon numbers in the distal graft compared to the proximal graft. The ratio of myelinated axon numbers in the distal graft compared to the proximal graft was ~85-100% in isografts but ~55-68% in ANAs. Gene expression analysis within grafts is ongoing to determine (1) why ANAs decrease axonal regeneration within nerve grafts and (2) differences between single and chained grafts.
Conclusions: Minimal axonal loss and no functional deficit were identified with an additional suture line in an isograft repair. Axonal regeneration across an additional suture line in ANAs has a moderate effect on axonal regeneration. The need to coapt multiple isografts to achieve a desired length does not limit axonal regeneration over short distances and is advantageous compared to the alternative ANA.
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