Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury

Abstract

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.

Serial Changes in Bladder, Locomotion, and Levels of Neurotrophic Factors in Rats with Spinal Cord Contusion

“…Continuous intramedullary infusion of BDNF, for example, enhanced functional recovery in rats with compressed spinal cords (Namiki et al, 2000). NT-3 promoted axonal sprouting acutely across the midline in injured spinal cord (Chen et al, 2006) and reduced glial scar formation (Taylor et al, 2006). Genetically modified fibroblasts that release both BDNF and NT-3 promoted recovery of the neurogenic bladder following spinal cord injury in rats (Mitsui et al, 2005).…”

“…For example, NT-3 promoted axonal sprouting and reduced glial scar formation (Chen et al, 2006;Taylor et al, 2006) and BDNF increased early functional recovery, axonal growth, proliferation of Schwann cells, and formation of peripheral myelin (Bregman et al, 1997;Namiki et al, 2000). Administration of BDNF and NT-3 also promoted the recovery of bladder function (Mitsui et al, 2005).…”

Neural ECM mimetics

“…In diffusion-based delivery systems, the amount of the released compound can be regulated by physical characteristics, such as the pore size or the degree of porosity, or by the degradation rate of the material (Houweling et al, 1998;SakiyamaElbert et al, 2012). Drug delivery can also be achieved by affinity-based systems (Taylor et al, 2006), which allow the controlled release of a substance. An additional possibility is the covalent attachment of the compound to the material (Tian et al, 2005).…”

“…The use of fibrin scaffolds is safe, lacking side effects. And manipulation of fibrin to create delivery systems that can be used for controlled release of bioactive factors has been tested extensively and yielded positive effects ( Johnson et al, 2010;SakiyamaElbert et al, 2012;Taylor et al, 2006).…”

Forever Young: How to Control the Elongation, Differentiation, and Proliferation of Cells Using Nanotechnology

“…combine the properties that are unique to each (55). They include alginate (26,27,41), chitosan (6,13,14), collagen (1,34), fibrin (21,(42)(43)(44)(48)(49)(50), and hyaluron Drawbacks. Degradation by-products can be ab- (18,19,24,52).…”