Repairing Nerves With Allograft
Repairing peripheral nerves is a medical problem that still lacks a natural, compromise-free solution. Until now. AxoGen’s AVANCE Nerve Graft is made of minimally processed human nerve tissue, and although it is still new to the market, it already promises to revolutionize peripheral nerve repair. This new technology works where traditional treatments have faltered, and it is safe enough to calm the nerves of surgeons and patients alike.
Jamie Grooms, CEO of AxoGen, explains the basic principle behind AVANCE Nerve Grafts: “we restore form to get function.” Mr. Grooms believes that the best way to heal the human body is to use the human body, and, frustrated with the limitations and negative side effects of alternative nerve repair treatments, he poured his time and resources into developing a method for using real, human nerves. Instead of sacrificing a patient’s own nerve tissue from a donor site, Mr. Grooms wanted to find a way to take nerve tissue from deceased organ donors and make it safe and easy to use with any patient. “My reasons for starting AxoGen where somewhat personal, ” explains Mr. Grooms. “I tried nerve grafting at another company and couldn’t get it to work—we just didn’t have the technology.” What Jamie didn’t know was the missing technology already existed.
In 1989, Dr. David Muir, working at the University of Florida, discovered naturally occurring inhibitory structures in peripheral nerves. He also found the enzyme needed to selectively remove the inhibitory structures. Chondroitin sulfate proteoglycans (CSPGs) inhibit axon regeneration, but by removing CSPGs, you can open the door to the nerve’s natural healing mechanism. Mr. Grooms remembers first learning about the discovery in Florida: “I thought I probably wouldn’t find anything there, but as soon as I saw it, I knew it would work. I put in the original seed money for the company, we got some venture capitalists on board, and here we are today.” That was in 2002.
The last missing puzzle piece came from the University of Texas. Between 1990 and 2000, Dr. Christine Schmidt developed methods of clearing cellular and non-cellular debris from tissue. This is vital for turning donated nerve tissue into clean, sterile nerve structures that can be used with any patient without fear of infection or tissue rejection. AxoGen licenses the technologies from the University of Florida and the University of Texas for the production of their AVANCE Nerve Grafts. Through contracts with LifeNet and other tissue banks throughout the US, AxoGen recovers tissue from organ and tissue donors with the consent from donor families. The nerves go through the patented process of decellurization and removal of CSPGs and then the individual grafts are sterilized, inventoried and frozen.
Because AxoGen only needs a small amount of tissue for each graft, they have no supply shortages, and they can offer a wide range of graft lengths from 15mm up to 50mm with varying diameters to best fit a patient’s damaged nerves. The AVANCE Nerve Grafts were released for distribution in 2007. Currently, AxoGen distributes their grafts directly to hospitals and surgeons as well as through a license with Stryker. The nerves arrive frozen, thaw in 5-10 minutes prior to surgery, and doctors use the same techniques they already use with nerve autografts to surgically implant the AVANCE Nerve Graft.
Before the AVANCE technology, surgeons often repaired a damaged nerve with a conduit or a nerve autograft. A nerve autograft uses a patient’s own nerve, usually taken from the calf area, to reconnect and facilitate regrowth of the damaged nerves. Taking nerve tissue from another part of a patient’s body, however, requires more surgery and results in some loss of feeling and numbness at the donor site. A conduit, made of collagen material, provides a two-dimensional surface which bridges the gap between damaged nerves and encourages the tissue to heal and regenerate. Conduits, however, are limited to very short gap repairs.
Dr. Bauback Safa, hand and microvascular surgeon at the Buncke Clinic in San Francisco, has used AVANCE Nerve Grafts in 12 procedures, making him considerably well experienced with this new product. "The conduits, ” explains Dr. Safa, “are typically relatively stiff and difficult to pass a needle through, so they are a little more difficult to handle. They tend not to cross joint surfaces as well, and they tend to kink. I definitely would prefer to work with material that feels and handles in a similar manner to human nerves. The AVANCE Nerve Graft, since it is a human nerve, provides all the smaller axonal pathways the nerve axons can regenerate through, whereas the conduit is just a big tube so the nerve still has to really find its way. We've had unpredictable results with conduits despite some of the earlier studies saying that they work as well as autografts. In my opinion, the results are quite less predictable than nerve grafting.”
Dr. Safa prefers to work with real human nerves, but he still sees problems with using patient’s own donor tissue: "the autograft certainly adds operating time because you need to prep the donor site, and unless you have a second team to do it for you, which most people don't have, you need to go down there, harvest the nerve, come back up, finish the operation and then go back down and close the leg. That by itself can add anywhere from 15 minutes to a half an hour, and in OR time, that's thousands of dollars. You can imagine my patients are happy about not having to give up a sensory nerve and use something off the shelf instead."
Dr. Safa’s surgery on a 30-year-old construction worker’s hand highlights the ability of the AVANCE Nerve Graft to repair nerves where other methods fail. The patient sustained an injury to his left hand from a table saw damaging nerves and tendons. The gaps between healthy nerve ends were no longer than 20mm, and his hand was repaired with conduits. After 10 months, however, the patient had no measurable recovery in sensation. When Dr. Safa met the patient, his condition actually worsened, and neuromas in his hand caused him constant pain. Dr. Safa decided to reenter the wounded hand and repair the damaged nerves with AVANCE Nerve Grafts.
The patient was very apprehensive about a nerve being taken from his leg—he didn’t want the extra surgery and he didn’t want to lose any function or feeling from another part of his body. Fortunately, Dr. Safa was able to cut back the damaged nerve ends made worse by the conduits and close the now 30mm gap with AVANCE Nerve Grafts. The patient had feeling in his knuckles after five months, and he now has sensation up to the middle phalanx. Dr. Safa expects the recovery to progress steadily until the patient has feeling all the way back to his fingertips.
Although Jamie Grooms is pleased that his product succeeded where another method failed, he says “the reality is that the failed product shouldn't be used in the first place.” He hopes AVANCE Nerve Grafts will help repair damaged nerves the first time around so that patients will not have painful recoveries and multiple surgeries. Mr. Grooms gives another example of a successful use of AVANCE grafts in jaw repair. According to Mr. Grooms, thousands of patients every year are left with numb tongues and lower lips after the removal of a 3rd molar damages their lingual nerve. Because these patients may accidentally chew their tongues, they have to eat their food through a straw. AVANCE Nerve Grafts have successfully restored sensation to some of these patients as well.
Mr. Grooms says AxoGen’s grafts are designed to repair all types of peripheral nerves, but he is also looking forward to more challenging cases. “Successful outcomes in motor nerve reconstruction are trickier” explains Mr. Grooms. “You need to repair the nerve as soon as possible to increase the likelihood of functional recovery. The spinal accessory nerve, which allows you to shrug your shoulders, was an aggressive nerve reconstruction challenge, but our nerve grafts have successfully restored function back in early cases.” Mr. Grooms also believes that nerve grafts could potentially be used in the future to repair the ocular nerve and restore sight to the blind. “There is no research yet, ” says Mr. Grooms, “but these are areas for us to explore.”
For now, Jamie Grooms and AxoGen are concentrating on getting their product out of the freezer and into patients who need it most. Although there may be skeptics, converts like Dr. Safa agree that AVANCE Nerve Grafts are an excellent option for nerve repair. By guiding damaged nerves to heal themselves naturally, AVANCE Nerve Grafts restore form and function to patients. As Jamie Grooms says, “Why would you ever choose anything different?”