Investigators: Eric E. Sabelman, PhD and V. Rodney Hentz, MD Project Staff: R. Lane Smith, PhD; Deborah E. Kenney, MS OTR; Feng Zhang, MD; Alvin H. Sacks, PhD; David Terris, MD; Gregory M. Buncke, MD; and Edward Diao, MD Project Category: Spinal Cord Injury - 2000 Objectives: The goal of this project was to prepare for and conduct a limited clinical trial of a multi-component artificial nerve graft (ANG) as an alternative to a nerve autograft. Up to 10 patients per year were to have been recruited, starting 18 months into the project. The project had six goals, four of which were achieved: (1) adult human Schwann Cells (SC) were isolated and cultured; (2) assays and precautions necessary to insure absence of pyrogens and immunoreactive proteins were implemented; (3) complete fabrication of a human SC-seeded ANG was demonstrated (we cannot yet reduce the 2 to 6 weeks in culture needed for cell proliferation); (4) noninvasive methods were tested for evaluating motor and sensory recovery (tests for conduction velocity and sudomotor response need further development); (5) to date, no patients at VA Palo Alto HCS or Stanford have received ANG implantation; (6) the retrospective control group was too small for comparison of outcome matched for age, gender and type of injury. Results: Our experience has shown that patients requiring simple acute anastomoses or short autografts are unlikely to be recommended for the experimental ANG. Three patients were referred; all had long-standing nerve damage affecting multiple nerves; no implants were performed in these subjects. The ability of axons to traverse an ANG of length typical of clinical needs has been examined by Dr. Hentz and Medical Scholars student Mark Hong. Additional in vivo experiments were conducted: (1) ANG implantation using fibrin adhesive instead of sutures, (2) subcutaneous implantation of (a) coated hyaluronate and (b) phosphorylated (Nova-Gen) vs. UV-crosslinked (Zyderm) collagen sheath materials. As part of our effort to find alternative biomaterials, Dr. Min Hu developed a unique method of treating hyaluronic acid to limit dissolution and improve cell adhesion.. The process was submitted to Stanford Office of Technology Licensing; a patent application has been filed and a licensing option has been issued to a cosmetics company. Collaborations were established with: (1) the Immune Response Corporation (Carlsbad, CA), with whom we have submitted a pilot proposal to the Christopher Reeve Paralysis Foundation for experiments aimed toward spinal cord regeneration using ANGs; (2) Nova-Gen, Inc. (Fremont, CA) which has provided a small grant to support work in which its product, a chemically-processed Type I collagen, was compared to other collagen-based biomaterials. Funding Source: VA RR&D Merit Review |
