Nerve allograft

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Nerve allotransplantation (allo- means "other" in Greek) is the transplantation of a nerve to a receiver from a donor of the same species. For example, nerve tissue is transplanted from one person to another. Allotransplantation is a commonly used type of transplantation of which nerve repair is one specific aspect.

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The transplant is called an allograft, allogeneic transplant, or homograft. [1] Currently the only FDA approved nerve allograft is the Avance graft of AxoGen.

Nerve allograft

A nerve allograft is used for the reconstruction of peripheral nerve discontinuities in order to support the axonal regeneration across a nerve gap caused by any injury. It is human nerve tissue, processed to remove cellular and noncellular factors such as cells, fat, blood, axonal debris and chondroitin sulfate proteoglycans while preserving the three-dimensional scaffold and basal lamina tubular structure of the nerve. This means the nerve allograft only consists of extracellular matrix (ECM), which is sterile and decullularized. [1]

There are three types of nerves;

In a trauma or surgical resection, a nerve can be damaged, which is called a nerve defect. This defect needs to be repaired in order to regain full or partial sensory and motor function. Peripheral nerve injury is a major clinical problem and can result in neuropathic pain, which is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. Damaged nerve fibers continuously excite electric pulses, inducing pain or abnormal sensation dysesthesia. It has been shown that in allograft surgeries, post-operative neuropathic pain was present in some patients, but only if they had this condition pre-operatively. [2] Patients without neuropathic pain before their surgery did not complain about neuropathic pain afterwards. [2] Hence, allograft treatment does not seem to be a risk factor for this specific problem.

Golden standard therapy for transected nerves is an end-to-end repair of the nerve, also known as primary nerve repair. With a certain amount of tension on the nerve due to the injury, the blood flow to the nerve decreases, which can eventually lead to ischemia and nerve damage. The gap between the nerve ends could then, for example, be bridged by a nerve that is harvested from a less critical area from the same patient. The piece of nerve used in this case is called an autograft autotransplantation. [3] [4] [5] [6] [7]

A commonly used nerve for autotransplantation is the sural nerve in the upper leg. Unfortunately, this treatment does have some disadvantages. First, there is a risk of donor site morbidity and functional loss. Secondly, patients have an increased risk of symptomatic neuroma formation. Thirdly, a longer anaesthesia time is needed because of the additional surgical site for the donor nerve. Lastly, higher costs also due to the extra surgical site. Despite these downsides, reducing the function of the affected area is beyond the risks committed with harvest of the donor nerve. [4] [7] [8] In case of insufficient amount of autologous nerve tissue or the inability to attach both nerve ends securely and tension free, these two options are not possible.

Another option to bridge the gap is nerve allotransplantation. Nerve allografts are prepared from donated human nerve tissue. An allograft contains many of the beneficial characteristics of nerve autograft, such as three-dimensional microstructural scaffolding and protein components inherent to nerve tissue. [3] One of the adverse effects of nerve allotransplantation is the immunogenic response. Tissue from another human being is used to restore the defect, which can induce an immunogenic response. An immune response against an allograft or xenograft is called transplant rejection. To prevent this rejection, new immunosuppressive techniques are performed on the graft, before it is transplanted into the receiver. The donated nerve tissue is disinfected, by selectively removing cellular components and debris to cleave growth inhibitors and then terminally sterilized. [3] These procedures make the immunogenic response insignificant. Processed nerve allografts have now been used successfully to restore nerve continuity for over two decades.

History

Rhazes, a Persian doctor, was the first who mentioned nerve repair in 900 AD. Nerve regeneration, is described for the first time in 1795 and in 1885 the first nerve allograft transplantation was reported. [9] In 1945, after WWII, Sir Sunderland described the anatomy of the peripheral nerves and developed techniques to improve the outcomes of nerve repair. A successful regeneration for short allografts (<4 cm) was achieved. However, there was a period of failure to accomplish successful recovery for all the allografts longer than 4 cm. Therefore, 'The Peripheral Nerve Injury committee' did not support nerve allograft until, in the early 1970s the first successful clinical trials on longer grafts were reported by using a new combination of radiation and freeze-drying techniques. [4] Nowadays rejection is still an adverse effect of nerve allotransplantation, but modern immunosuppressive regimens are used to prevent this rejection. This is why these days, rejection has become a very rare complication and nerve allograft has become more relevant. [4]

Anatomy and physiology of nerves

Nerve Anatomy.jpeg

An axon is the part of a neuron which conducts electrical impulses. Axons are surrounded by myelin, which contain Schwann cells. Schwann cells improve the electrical conduction. The myelin is surrounded by endoneurium, which is a protective sheath of connective tissue. This is surrounded by perineurium and epineurium, of which the latter is the outmost layer of dense connective tissue. When it comes to nerve repair, it is crucial that those layers make a good connection.

Transplantation techniques

There are several kinds of organ transplantation techniques.

The nervus suralis, a nerve from the lower leg, is most often used. Consequently, the patient will miss the specific nerve used as an autograft; therefore a person's own nerves can not be used for an unlimited number of times.

Clinic

The surgery of an allograft nerve can be explained in a few steps. First the surgeon has to prepare the broken nerve to do the standard operation procedures. This means the surgeon has to examine the local tissue and resecting scar tissue if needed. The proximal and distal segments of the injured nerves should be debrided to healthy tissue by visual and tactile signs. After that, the surgeon measures the distance between both nerve ends as well as the diameter of the damaged nerve. The processed nerve allografts come in different sizes, so that a gap can be closed without unwanted tension. When he has chosen the right allograft nerve, the procedure is no different from when an autograft is used. The same applies to the microsurgery, that a surgeon may use to repair the nerve. This means the sutures which connect the allograft with the damaged nerve are placed in the epineurium. So all other important anatomical structures of the nerve are kept intact. [1]

Autograft vs allograft

There are several factors that help a surgeon decide whether he should choose a nerve-autograft or an allograft. The differences between autografts and allografts are discussed above. The use of nerve autografts has some disadvantages. One is that the surgeon always creates a defect on the 'donorplace', from where the nerve is taken. Another disadvantage is that when the defect is large, the amount of available autografts may be insufficient.

Nerve allografts bring a possible solution for these problems. Because allografts are human nerves, processed in such a way that the immune response against the transplant is not provoked, the procedure differs little from the autograft-procedure except for the fact that there is no need to create a 'donorplace' defect. Therefore, allografts can be used more often in the same patient than autografts.

After the nerve is repaired, whether it is by using an autograft or an allograft, wallerian degeneration will be seen distal to the coaptation. This means that the part of the nerve that lies distal to the breaking point starts dissolving. The other end of the nerve will then grow back in this direction. The surgeon's transplant then only functions as the shell through which this growth can take place.

Studies suggest that nerve allografts work just as good as nerve autografts and are therefore a good alternative to the classic nerve autograft. [5] [8]

Gap length

Currently nerve reconstruction is limited in length. There is a relationship between the length of the nerve gap and the level of recovery following nerve repair. Two large clinical studies have divided three different gap lengths: 5-14mm, 15-29mm and 30-50mm nerve gaps. After adjustment for technical failures. The nerve grafts of 5-14mm had a 100% meaningful level of functional recovery in both studies. For nerve grafts above 15mm is seen in both studies a meaningful recovery around 80%. It seems likely that a shorter nerve gap has a better recovery, but despite that a significant difference was not found. [5] [8]

Motor vs sensory nerves

Since some studies on nerve allotransplantation determined the outcomes of sensory, motor and mixed nerves separately, the meaningful recovery for each nerve type has been assessed. Comparison of these outcomes has found no difference in successful recovery. [5] [8] [10] In other words, the sensation and movement of the affected body parts, in most studies the forearm, equally improved. Successful recovery of all three nerve types was achieved in approximately 80 to 85% of cases. [5] [8] Mixed nerves had a slightly lower recovery rate than sensory and motor nerves, but the success rate was still within the range just mentioned. [5] [8] Concluding, allograft surgery can be appropriately used for the functional repair of nerve injury in sensory, motor and mixed nerves. [2] [5] [8] [10]

Conclusion

The use of nerve allografts is a relatively new development and therefore autografts are currently still used more frequently. Efforts are being made to determine which procedure, i.e. autograft or allograft surgery, is preferred for each nerve type, but more research needs to be done. No comparison of these two procedures has been made in one single clinical study, let alone in a randomized controlled trial. This specific study type is of crucial value for evidence-based medicine.

Related Research Articles

Skin grafting

Skin grafting, a type of graft surgery, involves the transplantation of skin. The transplanted tissue is called a skin graft.

Grafting refers to a surgical procedure to move tissue from one site to another on the body, or from another creature, without bringing its own blood supply with it. Instead, a new blood supply grows in after it is placed. A similar technique where tissue is transferred with the blood supply intact is called a flap. In some instances a graft can be an artificially manufactured device. Examples of this are a tube to carry blood flow across a defect or from an artery to a vein for use in hemodialysis.

Allotransplant is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts.

Neurotmesis is part of Seddon's classification scheme used to classify nerve damage. It is the most serious nerve injury in the scheme. In this type of injury, both the nerve and the nerve sheath are disrupted. While partial recovery may occur, complete recovery is impossible.

Microsurgery

Microsurgery is a general term for surgery requiring an operating microscope. The most obvious developments have been procedures developed to allow anastomosis of successively smaller blood vessels and nerves which have allowed transfer of tissue from one part of the body to another and re-attachment of severed parts. Microsurgical techniques are utilized by several specialties today, such as general surgery, ophthalmology, orthopedic surgery, gynecological surgery, otolaryngology, neurosurgery, oral and maxillofacial surgery, plastic surgery, podiatric surgery and pediatric surgery.

Anterior cruciate ligament reconstruction Surgical process

Anterior cruciate ligament reconstruction is a surgical tissue graft replacement of the anterior cruciate ligament, located in the knee, to restore its function after an injury. The torn ligament can either be removed from the knee, or preserved before reconstruction an arthroscopic procedure. ACL repair is also a surgical option. This involves repairing the ACL by re-attaching it, instead of performing a reconstruction. Theoretical advantages of repair include faster recovery and a lack of donor site morbidity, but randomised controlled trials and long-term data regarding re-rupture rates using contemporary surgical techniques are lacking.

Bone grafting Bone transplant

Bone grafting is a surgical procedure that replaces missing bone in order to repair bone fractures that are extremely complex, pose a significant health risk to the patient, or fail to heal properly. Some small or acute fractures can be cured without bone grafting, but the risk is greater for large fractures like compound fractures.

Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person.

The word "syngenic" or "syngeneic" means genetically identical, or sufficiently identical and immunologically compatible as to allow for transplantation. For example, it may be used for something transplanted from an identical twin. When the cells are collected from the same patient on whom they will be used, a graft is called autologous. Syngeneic refers to a graft transferred between genetically identical animals or people. A syngeneic graft is known as an isograft.

Nerve injury Medical condition

Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, peripheral nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.

Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

The aim of an articular cartilage repair treatment is to restore the surface of an articular joint's hyaline cartilage. Over the last decades, surgeons and researchers have made progress in elaborating surgical cartilage repair interventions. Though these solutions do not perfectly restore articular cartilage, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injuries or chondropathies. These treatments are especially targeted by patients who have articular cartilage damage. They provide pain relief while at the same time slowing down the progression of damage or considerably delaying joint replacement surgery. Articular cartilage repair treatments help patients to return to their original lifestyle; regaining mobility, going back to work and even practicing sports again.

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Smile surgery

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The cheek constitutes the facial periphery, plays a key role in the maintenance of oral competence and mastication, is involved in the facial manifestation of human emotion, and supports neighboring primary structures.

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Epineurial repair

Epineurial repair is a common surgical procedure to repair a nerve laceration via the epineurium, the connective tissue surrounding nerve fibers originating from the spinal cord. It is intended to allow the restoration of sensory function. When a nerve is lacerated or cut, repair is done by sewing the cut ends together through the epineurium to increase the potential of the proximal part growing correctly along the route the degrading distal part leaves behind. Usual sensation and mobility will not be an immediate result because nerves grow at a rate of approximately 1 millimeter per day, so it will take a few months to notice the final outcome. Research in use of nerve grafts and nerve growth factors is being done to speed recovery time.

Labral reconstruction Medical procedure

Labral reconstruction is a type of hip arthroscopy in which the patient's native labrum is partially or completely removed and reconstructed using either autograft or allograft tissue. Originally described in 2009 using the ligamentum teres capitis, arthroscopic labral reconstruction using a variety of graft tissue has demonstrated promising short and mid-term clinical outcomes. Most importantly, labral reconstruction has demonstrated utility when the patient's native labral tissue is far too damaged for debridement or repair.

Gingival grafting

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References

  1. 1 2 3 4 "Archived copy" (PDF). Archived from the original (PDF) on 2013-11-04. Retrieved 2013-11-03.{{cite web}}: CS1 maint: archived copy as title (link)
  2. 1 2 3 Yates D (2013) Processed nerve allograft for trigeminal nerve repair: safety and effectiveness in sensory nerve reconstruction. J of Oral and Maxillofac Surg. 71 (9), 14 – 15
  3. 1 2 3 Siemionow M. (2007) Nerve allograft transplantation: a review. J of reconstr microsurg. 23 (8), 511 - 520
  4. 1 2 3 4 Mackinnon S.E., Doolabh VB, Novak CB, Trulock EP (2001) Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg. 107. 1419–1429
  5. 1 2 3 4 5 6 7 Cho M.S. (2012) Functional Outcome Following Nerve Repair in the Upper Extremity Using Processed Nerve Allograft. J Hand Surg. 37 (11), 2340 - 2349
  6. ↑ Lundborg G. Nerve injury and repair: regeneration, reconstruction and cortical remodeling. 2nd ed. Philadelphia: Elsevier, 2005.
  7. 1 2 IJpma FF, Nicolai JP, Meek MF. Sural nerve donor-site morbidity: thirty-four years of follow-up. Ann Plast Surg 2006;57:391–395.
  8. 1 2 3 4 5 6 7 Brooks D.N. (2012) Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed and motor nerve reconstructions. Microsurgery. 32 (1), 1 - 14
  9. ↑ Albert E. (1885) Einige Operationen an Nerven. Wien Med Presse 26,1285–1288
  10. 1 2 Taras J.S. (2013) Allograft Reconstruction for Digital Nerve Loss. J Hand Surg. 38 (10), 1965 – 1971
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