New Tools Aid in Nerve Repair

Originally Published MDDI August 2002

R&D DIGEST

A new delivery system for peripheral nerve regeneration could eventually provide the basis for stem cell delivery and spinal cord repair. Developed by Shelly Sakiyama-Elbert, PhD, assistant professor of biomedical engineering at Washington University (St. Louis), the new system uses a nerve guide tube filled with a gel containing growth-factor proteins capable of stimulating nerve regeneration. The system has been shown to promote peripheral nerve regeneration in preliminary rat studies, according to Sakiyama-Elbert.

The researcher collaborated on the project with Susan E. Mackinnon, MD, who is the Shoenberg Professor of Surgery at Washington University Medical School. The method is based on use of an exogenous adhesive material capable of binding growth factors throughout the gel. This enables the growth factor proteins to remain in the gel for months because they are retained by the adhesive material.

The researcher explains that these binding sites can be tuned according to how fast the drug needs to be released for successful regeneration. The use of timed-release mechanisms is a key component of the system. Currently available systems are limited by the diffusion of proteins within a few days.

Sakiyama-Elbert is also attempting to create a protein that consists of a growth factor, a bi-domain peptide, a cross-linking site, and a substrate for an enzyme that cleaves the growth factor at just the moment a regenerating nerve cell would be migrating through the matrix. This cell-activated drug-delivery system would also be incorporated into a gel and delivered using a nerve guide tube.

In addition, Sakiyama-Elbert is working with John McDonald, MD, PhD, assistant professor of neurobiology at the university, on the use of these matrix systems for treating spinal cord damage. Although McDonald previously used embryonic stem cells to treat spinal cord injuries in rats, most of the stem cells died after transplantation.

Sakiyama-Elbert believes that the matrix and nerve-guide tube delivery system can provide a more hospitable environment for the cells immediately after transplantation. She speculates that the method may allow 50 to 75% survival of the stem cells.

According to the researcher, "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." She explains, "The scaffolds are drug-delivery systems consisting of protein matrices containing growth factors that are released in a sustained manner during tissue regeneration."

Sakiyama-Elbert notes that the scaffolds can be further modified by adding embryonic stem cells during polymerization, a process in which 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," she says.

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