Peptide-Incorporated Biomaterials Promote Regeneration of Peripheral Nerve Injuries

Peripheral nerve injury (PNI), commonly caused by various forms of trauma, may lead to numbness, muscle weakness, and even loss of motor and sensory function. Autologous nerve transplantation remains the clinical "gold standard" for repairing peripheral nerve defects. However, it has inherent limitations, including limited availability of donor nerves, donor-site morbidity, and mismatched nerve sizes. Biomaterials-based nerve guidance conduits offer promising alternatives, particularly when integrated with bioactive factors. Among these, the incorporation of peptides has attracted increasing attention due to its distinct advantages. Incorporated peptides provide precise guidance cues or biological signals to regulate the behaviors of neurons, Schwann cells (SCs), immune cells, and endothelial cells (ECs) after PNI, primarily by mimicking specific functional domains of proteins without the complexity or immunogenicity associated with full-length proteins. In addition, peptides allow facile structural modification, enabling tunable biological activity, and can be customized and conjugated with high precision to biomaterials. This review summarizes recent progress in peptide-incorporated biomaterials for facilitating axon elongation, enhancing SC support, modulating inflammatory microenvironments, and inducing vascularization to promote peripheral nerve regeneration, and discusses current challenges and future perspectives for their potential clinical applications.