However, the thickness of the myelin sheath was reduced in comparison to the groups without the aligned gel. The present data are in line with the results described by Ceballos et al. (1999) with regard to the nerve area and the number of regenerated fibers. Nevertheless, an improved myelin thickness was found with the implant of collagen with a supra-molecular organization (TPCLF). This Inhibitors,research,lifescience,medical could also be noticed in the ultrastructural findings as well as by polarizing microscopy. The

present results additionally revealed, together with the increase in thickness of the myelin sheath, that the supra-organized collagen implant favored a close to normal extracellular matrix reorganization Inhibitors,research,lifescience,medical during the regeneration process. It is important to emphasize that within the first hours following tubulization, the gap between the stumps is filled with a fluid that is rich in growth-supporting factors. The presence of the aligned collagen implant may have facilitated the retention of such substances, what may in turn stimulate cell migration into the Inhibitors,research,lifescience,medical structured scaffold. The acceleration of the initial steps of the regenerative process may lead to the improvement of myelination

and morphological characteristics described herein. In addition, due to the structural support given by the collagen implant with a supra-molecular organization, the migration of Schwann cells could be anticipated and optimized. This is also supported by the immunohistochemical data regarding the expression of p75NTR. The use of polarization microscopy LY294002 revealed important new features of the normal nerve, such as the wavy Inhibitors,research,lifescience,medical supra-organization (crimping of collagen fibers), which is similar to that described for tendons and tendinous cords of the

atrioventricular valves of the heart (Vidal 2003; Vidal and Mello 2008; Vidal and Mello 2009). This indicates that the collagen organization in the microenvironment of peripheral nerves provides, besides its structural Inhibitors,research,lifescience,medical role, a scaffold for the alignment of the axons within the nerve bundle. Thus, it is believed that the use of collagen with a supra-molecular organization Digestive enzyme facilitates the repair of the microenvironment of the nerve, resulting in more compact and organized mini-fascicles. Taking into account the discussed above, the authors believe that the tubulization technique associated with the use of naturally organized molecules of the extracellular matrix is an acceptable approach for peripheral nerve repair. The regenerative process associated with the supra-molecular organized collagen provided a dynamic environment, allowing for axonal regeneration and the proper reorganization of the extracellular matrix in a more close to normal fashion. This is desirable in order to re-establish nerve homeostasis and function. Nevertheless, further investigations focusing on the functional recovery will be necessary in order to support the present findings.