Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Abstract

Human adult peripheral nerve injuries are a high incidence clinical problem that greatly affects patients' quality of life. Although peripheral nervous system has intrinsic regenerative capacity, this occurs in an incomplete or poorly functional manner. When a nerve fiber loses its continuity with consequent damage of the basal lamina tubes, axon spontaneous regeneration is disorganized and mismatched. These phenomena translate in an inadequate nerve functional recovery and consequent musculoskeletal incapacity. Nerve grafts still remain the gold standard in peripheral injuries treatment. However, this approach contains its disadvantages such as the necessity of primary surgery to harvest the autografts, loss of a functional nerve, donor site morbidity and longer surgery procedures. Therefore, biomaterials and tissue engineering can provide efficient resources and alternatives to nerve injury repair not only by the development of biocompatible structures but also, introducing neurotrophic factors and cellular systems to stimulate optimum clinical outcome. In this chapter, a comprehensive state-of-the art picture of tissue-engineered nerve grafts scaffolds, their application in nerve regeneration along with latest advances in peripheral nerve repair and future perspectives will be discussed, including our own large experience in this field of knowledge.

In vivo Evaluation of Nanostructured Fibrin-Agarose Hydrogels With Mesenchymal Stem Cells for Peripheral Nerve Repair

“…These findings were later confirmed by the muscle histochemical analyses which clearly revealed slight, moderate and severe rhabdomyocytes atrophy in autograft, NFABNS and filled conduits groups, respectively. Finally, our results suggest that the use of NFABNS in PN repair promote an acceptable, and in some aspect equivalent clinical and functional recovery profile than the use autograft technique in the repair of 10-mm nerve gap in rats, being these results supported by comparable studies and engineered models (Georgiou et al, 2013, 2015; Jesuraj et al, 2014; Kappos et al, 2015; Pedrosa et al, 2017; Schuh et al, 2018; Wang and Sakiyama-Elbert, 2018).…”

“…In PNTE, bioartificial substitutes must have adequate structural, physical and biological properties to successfully repair nerve defects supporting, and ideally increasing, the regeneration process and functional recovery (Daly W. et al, 2012; Carriel et al, 2014a; Wieringa et al, 2018). From the surgical perspective, it is important that nerve substitutes may respond to specific anatomical requirements (e.g., length, diameter, number of fascicles), should be easy to handle and to suture to ensure an adequate tension-free PN repair, and should be available for use in a reasonable period of time (Carriel et al, 2014a; Gu et al, 2014; Pedrosa et al, 2017). In this regard, the current gold standard technique, the nerve autografts, effectively provides adequate biological and physical properties with an acceptable functional recovery.…”

“…Concerning the design of the NFABNS, they were generated by rolling thin layers of NFAH to generate consistent multilayered rods containing viable, proliferating (positive for Ki-67 and PCNA) and functional ADMSCs (Carriel et al, 2017d). In addition, this simple, fast and economic procedure has the advantage that it could be programmed some hours before the surgery, which may fulfill the time requirements for an opportune PN repair (Pedrosa et al, 2017; Zhang and Rosen, 2018). Moreover, the NFABNS has been demonstrated to be surgically easy to handle with adequate mechanical stability and flexibility, which allowed a tension-free repair just like nerve autografts.…”

“…Technically, this strategy was considerably faster and easier than the use of NFABNS alone or nerve autografts because repair was done following the conventional tubulization technique. Regarding the suitability of this combined strategy in PNs repair, it is well-accepted that the use of conduits containing intraluminal fillers, especially those containing cells, is able to enrich the regenerative microenvironment with the consequent enhance of PN regeneration and functional recovery (Pedrosa et al, 2017; Gonzalez-Perez et al, 2018; Ronchi et al, 2018; Tajdaran et al, 2018; Wieringa et al, 2018). In this study, the incorporation of NFABNS into NeuraGen ® conduits prevented the deformation or compression of these commercial devices during the period analyzed.…”

“…Over the recent years, a wide range of promising TE strategies have been described (see reviews, Daly W. et al, 2012; Carriel et al, 2014a; Wieringa et al, 2018). From a physical and structural point of view, important advances were obtained by the incorporation of aligned biomaterials or nanofibers to the regenerative microenvironment (Gu et al, 2014; Pedrosa et al, 2017). From the biological perspective, authors demonstrated a significant increase of PNs regeneration through the use of functionalized and biologically active biomaterials, the incorporation of growth factors and gene-based therapies and, especially, by the incorporation of biomaterials containing different cells sources (Zheng and Cui, 2010; Ladak et al, 2011; Lopatina et al, 2011; McGrath et al, 2012; Carriel et al, 2013, 2017c; Georgiou et al, 2015).…”