Advanced Nanoparticle-Engineered Platforms for Peripheral Nerve Repair: Multimodal Therapeutic Strategies and Clinical Translation.

Peripheral nerve injuries (PNIs) remain a major clinical challenge, with current surgical interventions often falling short of restoring full function. Nanoparticle (NP)-engineered platforms are emerging as transformative tools in peripheral nerve repair by enabling multimodal therapeutic delivery, spatiotemporal control of the microenvironment, and biomimetic structural support. In this review, we summarize the recent advances in the design of inorganic, polymeric, and hybrid NPs that deliver neurotrophic factors, anti-inflammatory agents, and genetic material with high precision. Functionalization strategies-ranging from conductive and piezoelectric materials to antioxidant and immunomodulatory components-enable dynamic regulation of cellular behaviors critical for regeneration. Integration of NPs into next-generation scaffolds, including smart-responsive conduits and bioactive matrices, enhances axonal guidance and Schwann cell support. We further discuss preclinical outcomes demonstrating robust functional recovery and address translational barriers, including NP toxicity, scalable fabrication, and regulatory considerations. Finally, we outline future directions involving theranostic systems and AI-guided design for personalized nerve repair. Collectively, NP-engineered systems represent a paradigm shift in peripheral nerve regeneration, offering a multifaceted approach that bridges material science, bioengineering, and clinical translation.