Platelet-Rich Plasma Combined with Low-Dose Ultrashort Wave Therapy Accelerates Peripheral Nerve Regeneration

Finding treatments that accelerate peripheral nerve regeneration, prolongation, and functional recovery remains a challenging task. Platelet-rich plasma (PRP) contains numerous growth factors and active proteins, and low-dose ultrashort waves (USWs) stimulate the formation of nerve-nourishing vessels, which are powerful for nerve regeneration. The goal of this study was to evaluate the synergistic effects of serial ultrasound-guided PRP injections combined with low-dose USWs radiation on peripheral nerve regeneration in a crush injury model. Fifty rabbits were equally and randomly divided into normal control, model, USW, PRP, and PRP+USW groups. The neurological function, electrophysiological recovery, and histological and morphological evaluation of regenerated nerves, as well as a targeted muscle recovery assessment, were performed to investigate the regenerative effect of PRP combined with USW therapy. Our results showed that the PRP+USW group had the better early axonal regeneration and displayed the earliest positive compound muscle action potential among the treatment groups. At postintervention week 12, a histological evaluation showed similar expression of the S-100 protein in the PRP+USW and normal control groups. Moreover, the morphological assessment revealed a significant increase in the myelinated nerve fiber density and diameter and myelin sheath thickness compared with the USW and PRP groups. The morphometry of the target muscles indicated the lowest reduction in the percent volume in the PRP+USW group, and an ultrasound examination of the targeted muscle showed the best improvement in stiffness and perfusion parameters at 12 weeks after crush injury. Thus, serial ultrasound-guided PRP injections combined with low-dose USW radiation exert a synergistic effect on accelerating functional axon recovery and decreasing atrophy of the target muscles in a crush injury model. Impact Statement This research describes that the application of platelet-rich plasma combined with low-dose ultrashort waves treatment exert a synergistic effect on accelerating peripheral nerve regeneration. With the extensive use of platelet-rich plasma and physical factors in regenerative medicine or clinical rehabilitation medicine, our findings may help establish effective strategies for repairing peripheral nerve injury.