Animal models in peripheral nerve regeneration: from biological mechanisms to translational therapies

Peripheral nerve injuries remain a major clinical challenge, as functional recovery is often incomplete despite advances in microsurgical reconstruction and rehabilitation strategies. Animal models have played a central role in advancing the understanding of peripheral nerve regeneration, providing essential insights into the cellular and molecular processes involved in nerve degeneration, repair, and functional recovery following injury. Furthermore, they remain important for evaluating the safety, efficacy, and translational potential of emerging therapeutic strategies. This review examines the contribution of animal models to peripheral nerve regeneration research, focusing on their role across the translational pathway from mechanistic investigations to preclinical validation. The biological basis of nerve regeneration is discussed alongside the advantages and limitations of commonly used animal models, including rodents, rabbits, pigs, sheep, and non-human primates. The review also discusses how these models have been used to evaluate growth factor-based therapies, stem cell and cell-free approaches, biomaterials, nerve guidance conduits, bioelectronic interventions, and gene-based strategies. Current translational challenges, including species-related differences, long-gap defects, outcome assessment, and ethical considerations, are also addressed. Finally, emerging directions in regenerative medicine, bioengineering, extracellular vesicle therapies, advanced biomaterials, and gene modulation are explored. Collectively, the evidence highlights the continuing importance of animal models in bridging fundamental discoveries and clinical implementation, while emphasizing the need for clinically relevant preclinical frameworks to improve the translation of regenerative therapies for peripheral nerve repair.