*6.2. Conduit Architecture*

Electrospun collagen/poly(lactic-*co*-glycolic acid) (PLGA) conduits with a three-dimensional internal structure induce more extensive axon regeneration than conduits without a three-dimensional structure [180]. Functional recovery through conduits filled with pure fibrin gel is significantly increased when three-dimensional collagen tubes are filled with gelatin containing biodegradable poly-epsilon-caprolactone and collagen/ poly ε-caprolactone (PCL) sub-micron scale fibers [181].

#### *6.3. Conduits Containing Neurotrophic and Other Factors*

The e fficacy of collagen conduits is increased when they contain, or release, neurotrophic or other factors, such as GDNF [180] or neurotrophin-3 (NT-3) [182]. Alginate/chitosan conduits induce more extensive axon regeneration when they contain or release simvastatin [183], NGF [184–187], GDNF [184], VEGF [188], GDNF and NGF [24,189], or pleiotrophin [15]. E fficacy is also increased when alginate/chitosan conduits are combined with fibronectin, laminin [190], or when hydrogel conduits contain Matrigel, collagen, heparin (sulfate), laminin, or fibronectin [190]. Conduit e fficacy is further increased by the release of neurotrophic factors within conduits from biodegradable polymeric with aligned heparin-conjugated nanofibers [191,192].

Although pure fibrin-filled conduits induce axon regeneration [153], this influence is increased by adding neurotrophic and other axon regeneration-promoting factors [59]. This increase in e fficacy is due to the fibrin binding the growth factors, such as basic fibroblast growth factor (bFGF) [65], NGF, BDNF, and NT-30 and factors from the PDGF/VEGF, FGF, and tumor growth factor-beta (TGF-β) families [73]. Fibrin also facilitates the promotion of axon regeneration by binding Schwann cell-released extracellular matrix factor laminin [59]. The binding of these factors converts the fibrin from a passive to a potent regeneration-promoting three-dimensional matrix. This influence is supported by data showing that the application of neurotrophic factors within fibrin glue to the sites of nerve stump anastomosis significantly increases axon regeneration compared to applying the factors directly without fibrin [73,193]. Regeneration is also enhanced by infusing conduits with FK506, an immunosuppressive agen<sup>t</sup> [109,194].
