Peripheral nerve injury: current challenges, conventional treatment approaches, and new trends in biomaterials-based regenerative strategies

Damage to peripheral nerves is a widely extended health problem, causing important socio-economic costs worldwide. Indeed, peripheral nerve injuries (PNI) have been concerning the medical community for many decades. Nevertheless, despite the increase in knowledge in the injury physiopathology and the great research efforts being undertaken, the current standard grafting strategies used to repair PNI are not as efficient as desired. Although alternative engineered nerve grafts are already commercialized, their clinical performance is suboptimal. In this review, a general description of the circumstances and repercussions surrounding the PNI pathological state are presented, together with the treatment limitations and current challenges when addressing both short- and long-gap defects. In addition, potential therapeutic molecules are considered, while innovative regenerative strategies have been identified. Finally, the most relevant advances on the use of a wide range of biomaterials for the development of novel medical devices are also overviewed in depth, either considering strategies making use of empty or filled nerve conduits for guided tissue regeneration.This work has received funding from the European Community’s Seventh Framework Programme (FP7- HEALTH-2011) under grant agreement 278612 (BIOHYBRID), from ERDF/POCTEP 2007-2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the ComplexiTE − An integrated multidisciplinary tissue engineering approach combining novel high-throughput screening and advanced methodologies to create complex biomaterials-stem cells constructs (ERC-2012-ADG_20120216- 321266). Portuguese Foundation for Science and Technology (FCT) is also acknowledged for the funds provided under the program Investigador FCT to J.S.C. (IF/00115/2015) and J.M.O. (IF/00423/2012 and IF/01285/2015).