The overwhelming use of rat models in nerve regeneration research may compromise designs of nerve guidance conduits for humans

Rats are not the best model for the evolving complexities we face in designing nerve repair strategies today. The development of effective nerve guidance conduits for nerve regeneration is severely limited by the rat sciatic nerve model as the almost exclusive research model in academia. An immense effort is underway to develop an alternative to autologous nerve grafts for the repair of nerve defects, aiming particularly at larger gap repairs of 5-30 cm or more. This must involve combinations of ever more complex components, which in the vast majority of cases begin their testing in the rat model. Three major problems are at play: (1) The majority of nerve regeneration data is now being generated in the rat, which is likely to skew treatment outcomes and lead to inappropriate evaluation of risks and benefits. (2) The rat is a particularly poor model for the repair of human critical gap defects due to both its small size and its species-specific neurobiological regenerative profile. (3) Translation from rat to human has proven unreliable for nerve regeneration, as for many other applications. We explore each of these facets and their implications, in order to highlight the need for appropriate awareness in animal model selection when translating nerve regeneration modalities of ever-increasing complexity-from relatively simple devices to drug-device-biologic combinations.