The study protocol was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (approval No.II2024-022-01). Patients with peripheral nerve injury who have received PRP therapy in the rehabilitation department of Third Affiliated Hospital, Sun Yat-sen University were enrolled from January 2021 to March 2025. The general information were collected based on medical records, including patients’ name, gender, age, affected side, affected nerves, duration, etiologic diagnoses, medical histories, the number of PRP injections received, as well as their treatment frequency.

PRP therapy was not administered as a first-line intervention. All enrolled patients had previously received and failed standard conservative treatments for peripheral nerve injuries, including physiotherapy, exercise rehabilitation, corticosteroid injections, and glucose hydrodissection. The duration of prior conservative treatment was at least 3 months in most cases, without satisfactory clinical improvement. Therefore, in this patient population, PRP was used as a later-line, rescue therapy rather than a first-line intervention.

Regarding cohort composition: The study cohort consisted primarily of patients with compressive neuropathies (e.g., carpal tunnel syndrome, cubital tunnel syndrome, common peroneal nerve entrapment), which share similar underlying pathophysiological mechanisms. A small number of patients had other etiologies (toxic, ischemic, or traumatic nerve injury without complete transection). Given the limited sample size—reflecting that PRP is expensive and few patients receive it for peripheral nerve injuries—we pooled all eligible cases to achieve sufficient statistical power for exploratory analyses. The primary objective was to explore the potential applicability of PRP across different peripheral nerve disorders, not to compare efficacy across etiologies. The etiology classification of peripheral nerve injury cases treated with PRP is shown in Table 1.

Inclusion criteria encompassed the following: 1) Diagnosis of peripheral nerve injury confirmed by clinical presentation (motor and/or sensory deficits in a peripheral nerve distribution), electrodiagnostic studies (nerve conduction studies and/or electromyography), and/or neuromuscular ultrasound; 2) Failure to respond to standard conservative treatments (including physiotherapy, exercise rehabilitation, corticosteroid injections, and/or glucose hydrodissection) prior to PRP injection; 3) Received ultrasound-guided PRP injection for the diagnosed peripheral nerve injury; 4) Age ≥18 years; 5) Ability to comply with the clinical follow-up requirements (1, 3, and 6 months post-injection).

Exclusion criteria: 1) The injured nerve underwent surgical treatment (e.g., functional reconstruction surgery) during the follow-up period; 2) Presence of a malignant tumor or other life-threatening condition that precluded completion of the 6-month follow-up; 3) Lost to follow-up (missing ≥2 consecutive visits).

PRP was prepared using a double-centrifugation method with a commercial kit (TriCell PRP preparation kit, Rev-Med Inc., Korea). Approximately 30 mL of venous blood was drawn from each patient into sterile tubes containing anticoagulant (citrate dextrose). The blood was first centrifuged at 3,000 rpm for 4 min to separate red blood cells from plasma. The supernatant (plasma and buffy coat) was then centrifuged at 3,300 rpm for 3 min to concentrate platelets. The final pellet was resuspended in a small volume of plasma, yielding approximately 3.5 mL of PRP per patient.

The PRP used in this study was leukocyte-rich PRP (LR-PRP). Based on previously published data characterizing the TriCell preparation system, this method consistently achieves an approximately 3.0-fold enrichment of platelets over whole blood baseline, with significantly elevated leukocyte concentrations (10.09 ± 4.29 × 10³/mL, predominantly lymphocytes and monocytes) compared with whole blood (approximately 5.09 × 10³/mL) [13]. Quality control tests performed in our laboratory confirmed the reproducibility of this preparation method, consistently achieving a 3- to 5-fold platelet enrichment corresponding to a final platelet concentration of approximately 1,000 × 10⁹/L (1,000,000 platelets/μL), with leukocyte concentrations significantly above whole blood baseline.

However, due to the retrospective nature of this study, platelet and leukocyte counts were not systematically recorded for individual patients at the time of each injection, and we were unable to report exact cell concentrations for the full cohort. To ensure the consistency of our preparation method throughout the study period, we implemented a quality control protocol, performing validation assays (including platelet and leukocyte counts) on a monthly basis. These tests confirmed the reproducibility of the preparation method across different batches.

All PRP injections were performed under ultrasound guidance. The volume injected per nerve depended on the size and location of the affected nerve (the PRP preparation yielded approximately 3.5 mL per patient, which was typically sufficient for one nerve; for patients with bilateral or multiple nerve involvement, a single PRP preparation was sometimes divided between nerves).

The ultrasound-guided injection technique for PRP varied depending on the diverse anatomic locations of the peripheral nerves, consistent with the injection method outlined in previous research [14]. In summary, the procedures involved the following steps: Firstly, the lesion site of the nerve to be injected was precisely pinpointed through ultrasound examination by an experienced rehabilitation physician. Secondly, an appropriate puncture route is chosen, and the puncture area is thoroughly disinfected to ensure sterility. Thirdly, the puncture is precisely conducted under real-time ultrasound guidance, as demonstrated in Figure 1. Once the puncture needle is positioned adjacent to the target nerve, PRP is gently injected,to make sure that the nerve was surrounded by PRP liquid. Lastly, following the injection, patients are observed in the injection room for a minimum of 10 min to monitor any immediate reactions or complications.

The number of PRP injections and the intervals between them were determined based on the patient’s clinical response, with a generally recommended interval of 1–2 weeks. The majority of patients (approximately 75%) received 2 to 4 injections at 1- to 2-week intervals. Deviations from this schedule occurred in some cases: a few patients received only a single injection, primarily due to financial constraints, transportation difficulties, or unrealistic expectations regarding the speed of therapeutic response—despite being advised that clinical improvement may require time to manifest. Conversely, one patient received up to 8 injections, as each prior injection yielded noticeable improvement, and the patient strongly requested continued treatment.

Safety was assessed at each follow-up visit (1, 3, and 6 months post-injection). Using a structured interview format, all patients were systematically asked about the following potential adverse events: Pain at the injection site; Swelling, redness, or warmth; New or worsening numbness or paresthesia; New or worsening weakness; Any other new symptoms since the previous visit.

All adverse events were recorded and categorized by type, severity, and duration.

Continuous variables are presented as mean ± standard deviation (SD) if normally distributed or median with interquartile range (IQR) if non-normally distributed. Categorical data are expressed as proportions (%).

No a priori sample size calculation was performed, as this was a retrospective, exploratory study. The sample size was determined by the number of eligible patients treated during the study period.

Patients were stratified by symptom duration: <1 year vs. ≥1 year. Improvement rates (proportions achieving clinically meaningful sensory and motor improvement) were compared between duration subgroups at 1, 3, and 6 months post-injection using chi-square or Fisher’s exact tests. We performed 3 comparisons (at 1, 3, and 6 months) for each outcome. To address the risk of type I error due to multiple testing, we applied a post-hoc Bonferroni correction. With 3 comparisons, the corrected significance threshold was α = 0.05/3 = 0.0167. After applying this correction, none of the comparisons remained statistically significant. Therefore, our findings should be considered hypothesis-generating and exploratory rather than confirmatory.

To address the concern that a ≥1-grade improvement in MRC score may overestimate clinical benefit in patients with mild baseline deficits, we performed a sensitivity analysis restricted to patients with baseline MRC <3 (n = 16). In this analysis, motor improvement was redefined using a stricter criterion: achievement of MRC grade ≥3 (movement against gravity).

A total of 37 patients were included in this study, of which 11 patients presented with bilateral nerve injuries, resulting in a total of 48 cases receiving injections on the affected side. The general information of the patient undergoing PRP therapy is presented in Table 2.

Table 3 outlines the distributions of injured peripheral nerves that undergo PRP treatment. Notably, median nerve injury was the most commonly treated peripheral nerve with PRP. Occasionally, more than two nerves were injected simultaneously.

A month after PRP therapy, sensory function enhancement peaked, while motor function improvement was most evident 3 months later, as shown in Table 4. It is noteworthy that the motor function of 13 nerves was normal at baseline.

To address the concern that bilateral cases from the same patient may violate the assumption of independent observations, we performed a patient-level sensitivity analysis including only the more severely affected nerve for patients with bilateral involvement. The results were compared with the original nerve-level analysis.

As shown in Table 5, the responder rates were similar between the two analyses across all time points for both sensory and motor outcomes. Cohen’s h effect sizes ranged from 0.02 to 0.14, all well below the threshold for a small effect (0.2), indicating high consistency. This sensitivity analysis confirms that our main conclusions are robust and not substantially influenced by the inclusion of bilateral cases.

Among the 16 patients with baseline MRC <3, we compared the primary definition (≥1-grade increase) with a stricter definition (achieving MRC grade ≥3). The results are shown in Table 6. At 6 months, the improvement rate was 75.0% (12/16) under the primary definition and 68.8% (11/16) under the stricter definition, with an absolute difference of 6.2%. This indicates that most patients who achieved a ≥1-grade improvement by 6 months also reached the clinically meaningful threshold of MRC ≥3.

In an exploratory subgroup analysis, patients were divided into Group A (symptom duration <1 year, n = 25 for sensory, n = 20 for motor) and Group B (symptom duration ≥1 year, n = 23 for sensory, n = 16 for motor), as shown in Table 7.

For sensory improvement, the responder rate at 6 months was 80.0% in Group A versus 56.5% in Group B (p = 0.08), which did not reach statistical significance but suggested a trend toward better outcomes in patients with shorter symptom duration.

For motor improvement, the responder rate at 6 months was 85.0% in Group A versus 50.0% in Group B (p = 0.034), as shown in Table 7. However, after applying Bonferroni correction for multiple comparisons (3 comparisons: 1, 3, and 6 months; corrected α = 0.05/3 = 0.0167), this p-value no longer remained statistically significant. Given the post-hoc nature of this analysis and the limited sample size, this finding should be interpreted as hypothesis-generating and requires validation in future prospective studies with pre-specified subgroup hypotheses.

For the subgroup analysis comparing patients with symptom duration <1 year versus ≥1 year, we performed 3 independent comparisons (at 1, 3, and 6 months). The same Bonferroni correction (α = 0.0167) was applied. The observed p-value of 0.034 for motor improvement at 6 months did not remain significant after correction. This subgroup analysis was post-hoc and underpowered; the findings should be interpreted as preliminary observations requiring validation in future studies.

A total of 37 patients (48 nerves) received perineural PRP injections. One adverse event was observed, occurring in 2.7% of patients (1/37) and 2.1% of nerves (1/48).

Description of the event: In this case, the needle tip inadvertently penetrated the epineurium, resulting in partial intraneural injection of PRP. The patient experienced transient dysesthesia in the affected nerve distribution, which resolved completely within 2 months without any specific intervention.

No other adverse events were reported. Specifically, there were no cases of infection, hematoma, persistent pain, permanent neurological worsening, or allergic reactions. For all injections in which the needle tip was confirmed to be positioned outside the epineurium, no adverse events occurred.

Several limitations should be acknowledged. This was a retrospective, single-arm study without a control group, which limits causal inference and may overestimate efficacy. The number and intervals of PRP injections varied in real-world practice, and a dose-response relationship cannot be excluded. Our outcome measures also have inherent limitations: MRC improvement defined as a ≥1-grade increase may overestimate benefit in patients with mild baseline deficits, and patient-reported NRS scores cannot fully distinguish analgesic effects from true sensory restoration. In addition, pre- and post-treatment electrodiagnostic data were unavailable for most patients, limiting objective assessment of nerve regeneration.

Given these limitations, our findings should be interpreted as preliminary and hypothesis-generating. Prospective, randomized controlled trials are needed to confirm the efficacy of PRP for peripheral nerve injuries.