More recently, it has been proposed that aligned scaffolds made of natural or synthetic materials, could improve

axonal growth and facilitate the correct reattachment between the stumps inside the tube (Verdú et al. 2002; Kijeńska et al. 2012; Wang et al. 2012). Such scaffolds would also allow an increase in the gap between the proximal and distal stumps, which is one of the main advantages of the autograft repair approach. The use of functional molecules that may have autoassembling characteristics can facilitate the construction of organized Inhibitors,research,lifescience,medical scaffolds. Thus, the architecture of the collagen fibers plays a critical role in determining the biomechanical behavior of the extracellular matrix, and the alignment and GDC-0994 in vivo organization of its fibers depend on the function of the tissue in which they are found. Therefore, the collagen fibers of the extracellular matrix derived from tendons and ligaments are highly aligned to the long axis of the whole structure (Badylak et al. 2009). Nevertheless, the fibers and/or bundles of collagen tendons are not arranged in a flat structure, and Inhibitors,research,lifescience,medical the pattern of waves reflects the helical organization of the collagen fibers/bundles. Thus, the orientation of the tendon fibers can be considered as a complex structure with supramolecular organization (Vidal 2003; Vidal and Mello 2010). Axial sections of bovine tendons

treated with acetic acid Inhibitors,research,lifescience,medical and examined under polarized light support the supra-organization of helical bundles of collagen in these tendons, and a similar organization has been described in rat tendons (Vidal 2003). The organization Inhibitors,research,lifescience,medical and state of molecular aggregation of a biological implant are important factors that provide a suitable environment for axonal guidance and regeneration, and a naturally oriented protein can facilitate axonal growth and be degraded more efficiently (Fields et al.

1989; Labrador et al. Inhibitors,research,lifescience,medical 1998; Ceballos et al. 1999). In contrast, collagen, when subjected to different treatments, does not reproduce the helically organized pattern of fibers (Oliveira et al. 2005). The present authors previously showed that Schwann cells cultured on a naturally aligned collagen substrate expressed higher levels of the low-affinity receptor for neurotrophins (p75NTR) Thymidine kinase and for S100 (Pierucci et al. 2009). Also, cell orientation was enhanced when the cultures were established in the organized collagen substrate. It is possible that such a scaffold may provide a better support for regenerating axons if inserted into the gap between the nerve stumps using the tubulization technique. Thus, polystyrene scaffolds, produced so as to replicate the basal lamina of peripheral nerves, lead to a neurite alignment parallel to the structure of the basal-lamina like tubes obtained in the preparation (Karlsson et al. 2011). Another interesting approach to obtain longitudinal organization of the artificial implant was proposed by Lu et al.