However, despite articles showing some encouraging evidence the timing of growth factors and delivery is still being refined [ 29 ]. Application of electrical stimulation to peripheral nerves has shown to improve peripheral nerve lesions gaps but has shown to shorten the delay of fibers crossing the nerve injury site and not the speed of fiber growth. The effects of ES have shown to be only short lasting, with no difference in effect after three months [ 30 , 31 ].
Phototherapy is a new exciting frontier, that uses low-power laser therapy [ 32 ]. Despite improvements in axon regeneration and myelination, reports are limited to support the advantages of laser therapy [ 32 ]. Autologous biological tissues non-nerve grafts have been considered as an alternative as they would be immunologically compatible and non-toxic. However, harvesting samples with appropriate size and dimensions is difficult.
Tissues, which have proved useful in promoting a degree of axon regeneration, include blood vessels and freeze-thaw killed skeletal muscles [ 33 , 34 ]. A different approach is to use non-autologous sources, to bridge the gap between nerve lesions.
These tissues offer unlimited supply but have an associated immunogenic risk, including transmission of disease and graft versus host disease reactions. When constructing a nerve conduit for nerve repair, four elements need to be taken into consideration: Firstly the scaffold for axonal proliferation, then the support cells for Schwann cells and lastly the growth factors and extracellular matrix.
The scaffold serves to act as the structure for supporting axonal regeneration [ 37 ]. Natural materials have been tested including laminin, fibronectin and collagen due to their advantages of decreased toxic effect, improved biocompatibility and enhancement of the migration of support cells [ 37 ] but there is documented evidence that they loose their ability to regenerate when stored for long periods of time and there can be batch to batch variability [ 38 ].
Synthetic materials have been used and tested and although useful as can be manipulated to the exact configuration, long-term consequences of the conduit on the nerve are unknown. Support cells SCs have shown to enhance axon migration and produce structural and adhesive ECM molecules which promote nerve regeneration.
These growth factors as explained above, can be directly incorporated into the nerve conduit [ 42 - 44 ]. The extracellular matrix molecules are important for axonal extension and act as guiding the nerve regeneration.
It has been found that ECM molecules including fibronectin, collagen and laminin incorporated into the conduit, act as a guidance channel and have had variable results [ 45 , 46 ]. More recently nerve transfers are becoming more frequent. This procedure means less needed nerve fascicles from a donor nerve are transected, dissected and then attached to a more important distal nerve segment. This transforms a proximal nerve injury to a distal one with short regeneration [ 47 ].
This technique is useful for transferring nerve trunks in brachial plexus injuries. Gene therapy offers another exciting alternative to autologous nerve grafts for enhancing peripheral nerve repair. The main advantages are that the transduced cells will express the gene for an extended period of time which is useful as the neurotrophic factors inserted usually have a short half life [ 48 ].
Furthermore, the expression in the selected cells is restricted to the cell at the site of the injection of the viral vector meaning the therapy is selective, localised and specific. Various vectors are being trialed and tested with different types of neurotrophic factors but the main three cellular targets for gene therapy are the Schwann cells, injured neurons and the muscles fibers.
So far gene therapy has been successfully applied in rodent models to counteract the atrophy of spinal motor neurons following ventral root avulsion [ 49 ]. Furthermore, selective viral over expression of NGF in the sensory saphenous branch resulted in increased correct sensory reinnervation after injury, which could help the challenge of misrouting the regenerating sensory axons [ 50 ]. Lastly, studies have shown the long term expression of neurotrophic factors by Schwann cell in the injured nerve is possible with gene therapy [ 51 , 52 ].
Unfortunately, there are several obstacles preventing the translation of successful animal results to humans, including choosing the correct factor and target cell, biosafety regarding vectors and long term risk including mutagenesis. Over the last decade there has been extensive research into alternatives for surgical repair, as the clinical outcome often remains inadequate [ 53 - 56 ]. Although the concept of using a nerve conduit for peripheral nerve repair is quicker for the surgeons and avoids harvesting morbidity, it has not resulted in better outcomes in the literature so far.
Many growth factors have been indentified which influence nerve regeneration, which gives hope to the development of the ideal combination of growth factor and nerve conduit. It is clear that many conduits are currently being researched but they are still in their experimental stage with few being approved for clinical application. Similarly to other solutions for reconstructive surgery, the surgical advancements of the future to the surgical approach to peripheral nerve injuries will be focusing on cell and tissue modification and transplantation.
The authors confirm that this article content has no conflict of interest. National Center for Biotechnology Information , U. Journal List Open Orthop J v. Open Orthop J. Published online Jun Griffin M. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal.
Keywords: Anastamosis, biological replacements, clinical outcome, nerve repair, peripheral nerves. Neuropraxia Sunderland Type 1 This is an injury to the myelin sheath only [ 6 ]. Axonotmesis Sunderland Type In this type of injury the axon is affected and Wallerian degeneration occurs distal to the injury site [ 6 ]. Improving Autologous Nerve Grafts One idea which is being investigated, is the application of growth factors to peripheral nerve lesion sites to sustain the regenerative pathway of axons, which results in a down regulation of nerve growth factor expression [ 29 ].
Replacing Autologous Nerve Grafts Autologous biological tissues non-nerve grafts have been considered as an alternative as they would be immunologically compatible and non-toxic. The epidemiology and management of upper limb peripheral nerve injuries in modern practice.
J Hand Surg. Omer GE. Methods of assessment of injury and recovery of peripheral nerves. Surg Clin North Am. New and simple test of nerve function in hand.
Br Med J. Repairing injured peripheral nerves: Bridging the gap. Prog Neurobiol. Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration.
Mol Neurobiol. Seedon HJ, editor. Motor nerves have a time limit for healing. If the motor endplate receives no nerve impulse for more than months, it dies away and there is no longer any way that the muscle can be activated by the nerve. The muscle then whithers away.
Thus surgical repair of motor nerves needs to happen within months of the injury. Before sensation returns to the injured area, your limb is at risk of damage as it has no protective sensation. Please be careful of your hands or feet, especially around hot or sharp objects. Similarly, before the motor nerves recover your hand or limb may not be able to move normally or may develop abnormal postures.
Hand therapy or physiotherapy will allow movement to be maintained while the nerve cells regenerate. As your nerve recovers, the area the nerve supplies may feel quite unpleasant and tingly. This may be accompanied by an electric shock sensation at the level of the growing nerve fibres; the location of this sensation should move as the nerve heals and grows. Over time, these feelings subside and the area should begin to feel more normal.
Unfortunately, nerves never recover completely after they have been cut. I use a microscope or magnifying glasses loupes to repair your cut nerve with sutures finer than a human hair. This type of nerve repair surgery has the best recovery rates. Whether or not I can perform direct nerve repair on your injured limb depends on the injury your nerve has suffered. The traumatic laceration is usually extended and the wound is explored. Once the nerve has been identified, the extent of the injury is assessed.
The aim of a surgical repair is to restore the continuity of the nerve tube. Once a nerve tube has been cut, the nerve cell dies off. Surgery restores the continuity of the nerve tube through which the regenerating nerve cells will have a pathway to grow.
Often the nerves that are repaired are very small and the surgery may be carried out under a microscope. Once the nerve has been repaired and the wound closed, the region is often immobilised in a splint to prevent undue movement at the nerve repair site.
In these cases, additional procedures are available for reconstruction to restore lost function. Tendon transfer procedures are used to take working muscles adjacent to a paralyzed muscle, and substitute the movement of one muscle for another by reconnecting the tendons from the uninjured muscle to the injured one. Therapy will be initiated after the tendons have healed to learn the new movement from the transferred muscle and maximize function.
In an alternative procedure known as a nerve transfer, working nerve branches from adjacent uninjured nerves are reconnected to an injured nerve close to its connection to muscle to restore function.
By moving the recovering nerve endings much closer to the target muscles, the nerve transfers are able to restore function to muscles before the damage becomes irreversible.
After the nerve recovers, therapy is initiated to maximize the functional gains, as with standard nerve repairs. Sensation can also be restored with nerve transfers of working sensory nerves to nonfunctioning sensory nerves in a related procedure. If you would like to request an appointment with or refer a patient to the Division of Plastic and Reconstructive Surgery, please use the following contact information. Learn more about the Massachusetts General Hospital Division of Plastic and Reconstructive Surgery treatment options for nerve injuries.
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