Low-Intensity Pulsed Ultrasound in Peripheral and Central Nerve Repair: Mechanisms and Emerging Therapeutic Strategies

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Abstract
Low-intensity pulsed ultrasound (LIPUS) has emerged as a versatile, non-invasive physical modality with growing potential in regenerative medicine and neural repair. Advances in ultrasound physics and biomedical engineering have enabled precise spatiotemporal control of acoustic stimulation, positioning therapeutic ultrasound as an alternative to conventional pharmacological and surgical interventions that often suffer from limited targeting and substantial side effects. Unlike high-intensity focused ultrasound, which relies primarily on thermal ablation, LIPUS operates within a low-energy, non-thermal regime and modulates cellular behavior through mechanical cues, mechano-transduction, and downstream biological responses. Accumulating evidence demonstrates that LIPUS regulates calcium dynamics, cytoskeletal remodeling, neurotrophic factor expression, inflammation, myelination, and local vascular remodeling, thereby promoting functional recovery in both peripheral and central nerve injury models. Moreover, the integration of LIPUS with biomaterials, including piezoelectric scaffolds and acoustically responsive drug delivery systems, has expanded its functionality from direct stimulation to on-demand electrical signaling and controlled therapeutic release. Despite these advances, challenges remain regarding parameter standardization, mechanistic consistency, and clinical translation. In this review, we summarize the systems, parameters, and biological mechanisms underlying LIPUS, discuss its applications in peripheral and central nerve injury repair, and highlight emerging strategies and translational barriers toward intelligent, multimodal, and personalized ultrasound-based therapies.
Funding Information
  • National Key Research and Development Program of China (2023YFC2412502)
  • National Natural Science Foundation of China (82471403)
  • CAMS Innovation Fund for Medical Sciences (2024-I2M-3-016)
  • CAMS Innovation Fund for Medical Sciences (2025-I2M-XHXX-157)
  • Institutional Open Access Program (IOAP) of the University of Science and Technology of China

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