Side-to-Side Supercharging Allograft
Abstract
Peripheral nerves are the wires of the body. Signals are carried through nerves from the brain to the muscles and from the sensory organelles in the skin back to the brain. Injuries to these vitals structures, which occur in up to 5% of all traumas, can leave life-altering functional deficits. If the wires or nerve to the muscles in the arm are cut, those muscles do not work and the person cannot use that aspect of their arm. For some of the more devastating injuries, the arm may hang limply and uselessly. More common but still significant injuries may result in loss of sensation or more limited loss of muscle control. When a nerve is transected, the only hope for recovery is surgical repair. Unlike wires, when nerve ends are reconnected, they still cannot immediately transmit signals. Rather, the nerve fibers (called axons) die back to the level of injury and must regrow downstream to the end targets (muscle and sensory organelles). This process is very slow (axons regenerate at a rate of 1 mm/day or approximately 1 inch/month) and imperfect. Axon loss, misdirection, and failure to regenerate are all significant obstacles to functional recovery following nerve repair. Direct end-to-end repair gives the best chance for successful axon regeneration but is often not possible. Nerve stump retraction, resection of damaged nerve tissue, or traumatic nerve tissue loss result in gaps that must be spanned using nerve autograft, artificial nerve tubes, or nerve allograft spliced in between the cut nerve ends. Nerve autograft is considered the historical gold standard. Harvested from somewhere else in the patient s body, this graft material has supportive microscopic architecture, guidance cues, and specialized (Schwann) cells that nurture and direct regenerating axons. Unfortunately, the harvest of a "donor" nerve to use as the autograft requires a second surgical incision (with the associated morbidity), increased surgical time, and loss of sensation from wherever the donor nerve was harvested. Though typically a less functionally important nerve is sacrificed, pain and persistent paresthesias are reported to be problematic in 5%-10% of patients. Additionally, the amount of extra nerve tissue available to be used as autograft is limited. Nerve tubes are an "off-the-shelf" product that can guide nerve regeneration without any of the morbidity associated with autograft harvest but are only effective in very short (2-3 cm) gaps. Human nerve allograft is basically donated cadaver tissue that is processed in a way that makes it immunotolerant (otherwise it would be rejected by the patient) and has the convenience of conduits (an unlimited supply, no need for a second incision or the morbidity associated with graft harvest) but also has many of the benefits of autograft (including the supportive microarchitecture, some guidance cues, and some neurotrophic growth factors). Nerve allograft, however, lacks the essential Schwann cells found in autograft (these cells are removed in processing), and these cells must migrate into the allograft tissue (from the native nerve stumps) before axons will grow across the graft. While animal and clinical data suggest that nerve allograft works better than conduits and almost as well as autograft for short and medium gaps, it is much less effective for longer gaps in which axon ingrowth in extremely limited. Scientists have recently demonstrated that this seems to have something to do with the Schwann cells and, in particular, may be related to the stressful (on a cellular level) migration into the nerve allograft tissue that the Schwann cells must undergo. Another scenario in which Schwann cells have been implicated in poor axon regeneration is when a nerve repair has been delayed for too long. It turns out that while axons need Schwann cells to regenerate, Schwann cells need close contact with axons to remain healthy and capable of supporting the axons. In situations in whi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610662
Entities
People
- Jonathan Isaacs
Organizations
- United States Army
- Virginia Commonwealth University