Understanding the Mechanics of Nerve Repair

Mechanics-of-Nerve-Repair-Chart
Base assumptions for illustration series: Interstump gap length of approximately 10-15mm

 

  • Transected nerve repaired within 90 days of original injury
  • Transected nerve endings resected back to healthy tissue

Repair of a 3-4mm diameter nerve; Degradable conduit; Cross section illustration is at midgraft. Hours is ~0-48 hours; Days is about 2-7 days; Weeks is ~1-8 weeks; Months is ~2-12 months.

 

Nerve Autograft
Sural nerve is the most commonly used donor nerve but it is typically small diameter which often results in a size mismatch to the nerve being repaired. Furthermore, because they are smaller caliber, fascicular patterns (number and size of fascicles) often do not match fascicular patterns of the nerve being grafted1. Upon implantation, the tubes of the autograft are filled with debris (e.g. axons and myelin) and cells from the site where it was harvested. Within hours following implantation of a nerve autograft, the graft is revascularized and the cells begin clearing out debris in the tubes and preparing the structure to serve as a scaffold for regenerating axons (see Hours). Within days the tubes have been completely cleared, Schwann cells (SCs) line up in each tubes and regenerating axons begin spouting trying to find tubes to grow into (see Days). While some tubes remain empty, axon regeneration is well distributed throughout the entire cross section of the graft because of the organization of tubes in the nerve tissue that serves as an optimum physical scaffold for cell and axon in growth (even distribution of tubes throughout). Within weeks, the regenerating axons that have found a tube to guide it are close to bridging the entire length of the nerve gap (see Weeks). Over time these axons regenerate across the entire length of the graft then continue on to the target site e.g. muscle or skin. Over the next several months, these axons continue to mature (get thicker) and remyelinate (see Months) resulting in a new nerve segment (see Years).2

Hollow Tube Conduit
Within hours following implantation of a conduit, fluid containing inflammatory cells and secreted trophic factors fills the conduit (see Hours). Within days, a fibrin cable forms inside the tube. Regeneration cannot successfully occur within a conduit without the formation of this fibrin matrix, which serves an essential function as a physical bridge across the nerve gap and provides contact guidance for cells. Notably the thickness and quality of the cable, which effectively provides the total available regeneration area, is inversely related to the size of the conduit and often does not fill the entire volume of the tube or does not even form at all if the gap length is too long (see Days). Over the next several weeks following implantation, SCs infiltrate from both stumps and grow along the fibrin cable. Some of the SCs are able to line up and form aligned tubes making a structure that can physically guide regenerating axons across the nerve gap. Axon regeneration is centralized to where the fibrin cable forms. Some of these SC tubes remain empty and any regenerating axons that do not locate a SC tube to guide it get pruned back and die (see Weeks). Over time, axons that are able to find and regenerate within a SC tube grow across the entire length of the conduit and continue on to the target site e.g. muscle or skin (see Months). Timing for the stability of conduits is crucial. Conduits need to remain stable until regeneration occurs across the nerve gap but once regeneration has occurred, the conduit is useless and its continued presence is only a potential hazard which is why the majority of nerve conduits are composed of non-permanent materials that degrade or resorb over time.1 Depending on the size of the nerve discontinuity and on the type of injury, adequate nerve repair can be achieved (see Years).3,4

Processed Nerve Allograft
Since processed nerve allograft is available in a range of sizes; it can more readily be sized to match the nerve being repaired. Immediately upon implantation, processed nerve allograft provides multiple empty open tubes that provide a physical scaffold for axon and cell in growth. Within hours following implantation, the graft is revascularized and repopulated with cells before any meaningful regeneration can occur (see Hours). Within days, Schwann cells (SCs) line up in each tubes and regenerating axons begin spouting trying to find tubes to grow into (see Days). While some tubes remain empty, axon regeneration is well distributed throughout the entire cross section of the graft because of the organization of tubes in the nerve tissue that serves as an optimum physical scaffold for cell and axon in growth (even distribution of tubes throughout). Within weeks, the regenerating axons that have found a tube to guide it are close to bridging the entire length of the nerve gap (see Weeks). Over time these axons regenerate across the entire length of the graft then continue on to the target site e.g. muscle or skin. Over the next several months, these axons continue to mature (get thicker) and remyelinate (see Months) resulting in a new nerve segment (see Years).3,5,6,7

  1. Meek MF and Coert JH. Clinical Use of Nerve Conduits in Peripheral Nerve Repair: Review of the Literature. J Reconstruct Microsurg. Feb 202; 18(2):97-109.
  2. Lundborg G. A 25 Year Perspective of Peripheral Nerve Surgery: Evolving Neuroscientific Concepts and Clinical Significance. J Hand Surg. 2000; 25A: 391-414.
  3. AxoGen Internal Report: RD-001
  4. Dahlin LB and Lundborg G. Use of Tubes in Peripheral Nerve Repair. Neurosurg Clin N Amer. Apr 2001; 12(2): 341-352.
  5. Karabekmez FE, Duymaz A, Moran SL. Early Clinical Outcomes with the use of Decellularized Nerve Allograft for Repair of Sensory Defects Within the Hand. Hand (NY) 2009; 4(3): 245-9
  6. Whitlock EL, Tuffaha SH, Luciano JP, Yan Y, Hunter DA, Magill CK, Moore AM, Tong AY, Mackinnon SE, Borschel GH. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve. 2009; 39(6):787-99.
  7. Evans PJ, Midha R, Mackinnon S. The Peripheral Nerve Allograft: A Comprehensive Review of Regeneration and Neuroimmunology. Prog Neurobiol. 1994; 43: 187-23