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July 22, 2002
Biomedical engineer trips up proteins in nerve regeneration system
It's sticky, it's a gel, it comes in a tube, but this is no greasy kids' stuff. Rather, it's a novel delivery system for peripheral nerve regeneration that could have implications for successful stem cell delivery and spinal cord repair.
Shelly Sakiyama-Elbert, Ph.D., assistant professor of biomedical engineering at Washington University in St. Louis, has designed a system that employs a nerve guide tube filled with a gel containing growth factor proteins that stimulate nerve regeneration. Also part of the package are strategically placed sugars and peptides for binding in the gel matrix. The system has promoted peripheral nerve regeneration in preliminary rat studies.
The clinical Gold Standard for peripheral nerve regeneration involves taking a nerve from a donor site on the injured person's body and sewing the donor nerve in between the two ends of the injured nerve. Though the nerve is dead, it provides a pathway that can guide the regeneration of the injured nerve. This is problematic because it creates an injury to be addressed at the donor site, and there is a limit to the amount of donor tissue you can use from a patient. Furthermore, there is no guarantee that the donated nerve will come to life in a new site. Another alternative is the use of cadaver nerves, which runs a risk of rejection.
Sakiyama-Elbert, working with famed plastic surgeon Susan Mackinnon ,M.D., Syd. M. and Robert H. Shoenberg Professor of Surgery of the Washington University Medical School, places exogenous sticky material capable of binding growth factors throughout the gel, causing the growth factor proteins to remain in the gel for months because they keep tripping over the sticky material. These binding sites can be tuned according to how fast the drug needs to be released for successful regeneration. Timed release is a key component of her system, because a real limitation is having the proteins diffuse out in a day or two, which is the case with many currently used systems.
Sakiyama-Elbert recently presented these results at a conference hosted by the Plastic Surgery Research Council, April 18-20, in Boston. Her work is sponsored by the Whitaker Foundation.
Another approach to peripheral nerve regeneration that Sakiyama-Elbert is testing involves creating her own protein consisting of a growth factor, and two different domains, a cross-linking site and a substrate for an enzyme that cleaves the growth factor at just the time a regenerating nerve cell would be migrating through the matrix. This cell-activated drug delivery system is also incorporated into a gel and delivered from a nerve guide tube, and it's a great example of a new area known as biologically responsible materials.
Stem cells for spinal cord repair
She also is one of very few researchers looking into matrixes for spinal cord damage, such as the kind that actor Christopher Reeves suffered years ago and from which he is not recovered. She is collaborating with John McDonald, M.D., Ph.D., assistant professor of neurobiology at the Washington University School of Medicine. McDonald already has treated spinal cord injuries in rats with embryonic stem cells; the problem is that most of the stem cells died after transplantation. Sakiyama-Elbert is hopeful that her matrix/tube delivery system will allow 50 to 75 percent survival of the stem cells by providing a more hospitable environment for the cells immediately after transplantation.
"The overall goal of this direction of my research is to apply novel bioengineering technology to allow controlled release of growth factors from scaffolds that facilitate the regeneration of adult spinal cord axons through and beyond spinal cord lesions," Sakiyama-Elbert said. "The scaffolds are drug-delivery systems consisting of protein matrices containing growth factors that are released in a sustained manner during tissue regeneration."
The scaffolds can be further modified by adding embryonic stem cells during polymerization, a process where small molecules are combined together to form larger ones.
"The embryonic stem cells can repopulate the injured spinal cord and serve as a source of nerve growth factors during regeneration," Sakiyama-Elbert explained.
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