BBI Japan Editor
TOKYO Kuraray Medical (Tokyo), a developer and manufacturer of dental materials including Self-etching Primer, a dental adhesive, as well as other medical supplies and materials, is working toward commercialization of a peripheral nerve regeneration material that was discovered by assistant professor Yoshihisa Suzuki, MD, of the department of plastic and reconstructive surgery at Kyoto University Graduate School of Medicine (Kyoto).
Kuraray Medical is one of the wholly owned subsidiary companies of Kuraray Co. Ltd. (Osaka, Japan), a conglomerate which mainly manufactures chemical fibers, fine chemicals, synthetic fibers and functional resins.
A team of researchers led by Suzuki is developing a new product using freeze-dried alginate gel sponge after covalently crosslinking alginate, a naturally occurring bioabsorbable polysaccharide extracted from brown seaweed, with low cytotoxic reagent, and washing, to be used as a peripheral nerve regeneration material. So far, the Kyoto University team has demonstrated its effectiveness in healing feline sciatic nerves with 50 mm defects to almost normal levels.
The process is characterized not by suturing the severed nerve stumps, but rather by implanting two sheets of gel sponge slightly longer than the length of the gap overlaying the sheets on severed nerve stumps, thereby bridging the gap between the severed nerve stumps. In an early stage following implantation of the alginate sponge gel in the gap, it has been observed that the regenerating axon has elongated, using the gel sponge as a scaffold.
This indicates that the partially degraded alginate gel could prove to be a favorable environment for the elongation of regenerating axons and migration of Schwann cells. It also has been found that the thickness of myelinated nerve fiber tends to recover up to the thickness similar to that of the normal nerve in the long term.
Reconstruction of nerve defects 25 mm long has been the limit with conventional nerve regeneration materials. The work of the Kyoto University group has indicated that there is an apparent mechanism of action preventing the invasion of scar tissue that blocks the elongation of axons. The result is the creation of a porous structure that favorably enhances the elongation of axons and the transportation of nerve growth factors, as well as constituting an environment that inhibits the proliferation of fibroblasts within the gap. Because the gap was completely buried with a large volume of scar tissue in a control group in which nothing was implanted in the gap, only minimal axon regeneration was observed in that group. A number of thick myelinated axons were observed from the midpoint of the regenerated nerve tissue by light microscopic observation, and the implanted nerve regeneration material was completely absorbed without inflammation and foreign-body reaction. Many myelinated axons also were observed in the distal stump.
Suzuki's group has carried out electrophysiological evaluations by measuring compound muscle action potential (CMAP) and somatosensory evoked potential (SEP). The measurement of CMAPs was performed by electrically stimulating the sciatic notch and recording action potentials at the thigh gastrocnemius muscle under anesthesia. The measurement of SEPs was performed by stimulating thigh gastrocnemius muscle and recording action potentials at the head. A short latency equal to that of the normal nerve was observed in both CMAP and SEP records at three months after surgery.
Although conducted with a small number of cases, it was discovered through clinical studies that this method also is effective in the regeneration of human digital nerve gaps.
Since this material is using plant-derived raw material, the method has the advantage of avoiding potential risk of infections such as by pathogens represented by prions whose presence could be expected in animal-derived regeneration materials. Furthermore, the generation of scar tissue acts as a physical barrier against axon elongation at the nerve stump, which is the most serious disadvantage in the case of using nerve regeneration material derived from extracellular substrates such as collagen. That problem has already been solved in the case of alginate gel sponge.
While it has been reported that about 250,000 cases of nerve damage resulting from accidents or surgeries occur annually in Japan, no approved nerve regeneration material currently exists. Because of this, the current method is to transplant autograft harvested from the patient's sensory nerve, which creates a significant loss in the patient's quality of life resulting from the loss of senses in the areas governed by the harvested nerve. Furthermore, the harvesting of nerves may face shortages when the multiple numbers of thick nerves are required.
Kuraray Medical believes these problems can be overcome by using artificial materials, which have no supply limits. While conventional nerve regeneration materials have tubular forms requiring suturing its ends to severed nerve stumps of the peripheral nerves, the alginate gel sponge only needs to be put in place by way of wrapping around the severed nerve stumps. By not being in a tubular form, the alginate gel sponge nerve regeneration material discovered by Suzuki's group and focused on by Kuraray Medical can be used for repairing any kinds of peripheral nerves having any thickness.
With a goal of commercializing the technology by 2006, Kuraray Medical is seeking a global corporate partner for joint development of the nerve regeneration material.
Since effectiveness also has been observed in regenerating the spinal cord in infant and adult rats, the company is planning its development efforts with the regeneration of central nerve systems in the future as well. "Because gel sponge implantation does not require any dedicated instrument or special technique, this approach is promising as a nerve regeneration material characterized by ease of performing the procedure, while at the same time it is expected to expand its clinical applications as a cost-effective technology," said the company's research manager, Tadashi Hashimoto, PhD. " More importantly, this is the least-invasive procedure, minimizing a patient's pain."
As one of the options available for next-generation medicine, this technology appears to clearly benefit both physicians and patients. As in the case with endoscopes, the nerve-regeneration technology might be practiced not only by surgeons but by internists as well.