Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury.
Neurotrophins have been shown to promote axonal growth and regeneration after spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by using a controlled delivery system to increase the duration of neurotrophin availability following injury. Such a delivery system can be incorporated into a bioactive scaffold to serve as a physical bridge for regeneration. This study assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin scaffolds implanted in spinal cord lesions immediately following 2-mm ablation injury in adult rats. Nine days after injury, fibrin scaffolds containing the delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth into the lesion than did control scaffolds or saline (1.5- to 3-fold increase). Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar formation at the white matter border of the lesion. Hindlimb motor function of treated animals did not improve relative to controls at 12 weeks post-injury. Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial regenerative response by increasing neuronal fiber sprouting and cell migration into the lesion, while functional motor recovery was not observed in this model.
Taylor
Sara J
SJ
Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA.
Rosenzweig
Ephron S
ES
McDonald
John W
JW
Sakiyama-Elbert
Shelly E
SE
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement; D004195:Disease Models, Animal; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000145:classification / Q000187:drug effects* / Q000473:pathology; D009416:Nerve Regeneration; D020933:Neurotrophin 3 / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D004337:Drug Carriers; D004343:Drug Implants; D020933:Neurotrophin 3; D005337:Fibrin; D006493:Heparin