Presently, there are no effective therapies to restore function of nerves traumatized by mechanical cleavage. By applying a biocompatible and synthetic polymer, polyethylene glycol (PEG), the investigators have successfully restored the conduction of compound action potentials (CAP) in severed guinea pig spinal cord and peripheral nerves in vitro. However, the technique would not be successful for similar injuries in vivo due to the mechanical instability of the nerve trunk. The investigators are attempting to achieve mechanically stable nerve fusion by adhesively bonding the nerve connective tissue using surgical adhesives . Specifically, they will use two commercially available surgical adhesives and one experimental adhesive for anastomosing the severed nerve trunks after PEG-fusion of the cell membranes in an isolated sciatic nerve transection model. Their preliminary experiments with animal (guinea pig) connective tissue indicate that these adhesives would be able to provide the required mechanical stability to a new fused nerve trunk in vivo. The commercial adhesives used in the study (fibrin and cyanoacrylate) have been used in general surgery with manageable immune response. The experimental adhesive (Mussel Adhesive Protein) has been shown in published literature to elicit minimal immune response. The strong adhesive performance and reasonable biocompatibility of these adhesives compel the investigators to believe that these surgical adhesives are ideal candidates for nerve fusion studies using PEG. Their study will lay the groundwork for subsequent in vivo studies with guinea pigs. Use of surgical adhesives will enable PEG repair of transected nerves in vivo, which in turn will improve the post-injury quality of life of nerve-trauma victims. As part of the investigation, mechanical, electrophysiological and histological tests will be performed on uninjured guinea pig sciatic nerves to determine the critical functional tensile load (CFTL) of the nerve. ln the experiments, surgical adhesives will be used in conjunction with PEG on isolated and completely severed sciatic nerves, and the optimal conditions for PEG/surgical adhesive nerve fusion will be determined. Each surgical adhesive system will be evaluated using CFTL values as a standard for comparison. In addition, comparative immunological performance of each adhesive will also be determined using established procedures. Frequent consultation with a neurosurgeon, who is a member of the research team, will provide necessary input to direct the study and experiments towards clinically relevant solutions for transection nerve injuries.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD041371-01A1
Application #
6546664
Study Section
Special Emphasis Panel (ZHD1-RRG-K (SR))
Program Officer
Nitkin, Ralph M
Project Start
2002-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$73,375
Indirect Cost
Name
Purdue University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Nehrt, A; Rodgers, R; Shapiro, S et al. (2007) The critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma. Neuroscience 146:1504-12
Ninan, Lal; Stroshine, R L; Wilker, J J et al. (2007) Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa. Acta Biomater 3:687-94