Background: Because of the rising prevalence of anterior talofibular ligament (ATFL) damage, there is a considerable interest in developing innovative techniques to improve the biological healing response of ATFL. Platelet-rich plasma (PRP) includes several growth factors linked to a favorable healing response, however none of the studies involved both quality evaluation and clinical results to evaluate this treatment. Purpose: To determine the clinical results of PRP injections into the ATFL in lateral ankle sprain (LAS) patients, as well as the quality of the ATFL based on radiographic outcomes. Methods: Patients with clinically confirmed grade II LAS for the first time (n = 83) were examined. The clinical outcomes of three types of injection methods were evaluated: none, once within 48 h after the sprain, and once more 4 weeks later after first injection. PRP was injected into the tear site of the ATFL using ultrasound guidance, and all ankles were immobilized for 2 weeks. The American Orthopedic Foot and Ankle Score (AOFAS) ankle-hindfoot scale and the Visual Analogue Scale (VAS) were used to assess the results at 2, 6, 8, 24, and 48 weeks of follow-up. The signal/noise ratio (SNR) value of Magnetic Resonance Imaging (MRI)-based ATFL signal intensity can disclose ATFL quality. The ATFL SNR results were then assessed 8, 24 and 48 weeks following the first injection to compare ATFL quality. Results: The PRP injection groups outperformed the control group in terms of clinical outcomes, and the two injections group outperformed other groups in terms of pain reduction and functional outcome at 8 weeks. The clinical results of all groups were comparable at 6 and 12 months follow-up. ATFL SNR findings improved significantly across all groups over time. At the same follow-up time, the PRP injection groups outperformed the control group, and the best SNR result showed in the two injections group at the final follow-up. Conclusion: PRP injection helped relieve early symptoms of LAS, although all patients saw a similar development after 6 months. The two PRP injections group produced considerably better clinical results and quality of the ATFL in short-term follow-up.

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