Time-dependent growth factor kinetics, platelet concentration, and clinical response following platelet-rich plasma versus saline in chronic tenosynovitis: a randomized controlled trial

Abstract Background Platelet-rich plasma (PRP) therapy is utilized for chronic tenosynovitis to reduce inflammation and promote tendon sheath repair. This study compared the temporal kinetics of PRP-derived growth factors with clinical outcomes of PRP versus saline injection over 3 months. Methods In a randomized controlled trial, 200 patients with chronic tenosynovitis were assigned to non-activated PRP ( n  = 100) or saline ( n  = 100) tendon sheath injection. PRP group blood samples were collected at 1 h, 8 h, Days 1, 3, 7, 14, and 1 month post-injection; both groups had clinical and ultrasound assessments at 1 and 3 months. Serum VEGF, PDGF-AB, EGF, and TGF-β were quantified via ELISA, with platelet counts analyzed. Pain (VAS), function (WOMAC, DASH), and tendon sheath thickness were evaluated. Repeated-measures ANOVA and t-tests assessed changes. Results In the PRP group, non-activated PRP achieved a platelet concentration of 1030 ± 130 × 10³/µL (4.5× baseline), and biomarkers varied significantly ( p  < 0.001). VEGF peaked at Day 14 (285.44 ± 50.0 pg/mL), sustained at 260.0 ± 45.0 pg/mL (1 month). PDGF-AB peaked at 8 h (1253.28 ± 160.0 pg/mL), declining to 300.0 ± 90.0 pg/mL (1 month). EGF peaked at Day 7 (451.84 ± 75.0 pg/mL), returning to 380.0 ± 75.0 pg/mL (1 month). TGF-β exhibited plateau kinetics without a distinct peak, stabilizing at 8.50 ± 1.80 ng/mL (1 month). PRP outperformed saline in pain (− 50.0 mm vs. −31.0 mm), function (QuickDASH − 35.0 vs. −21.0), and sheath thickness reduction (− 0.9 mm vs. −0.4 mm) at 3 months (all p  < 0.001). PRP reduced VAS by 57% (30.0 ± 11.0 mm), WOMAC by 42% (35.0 ± 7.5), DASH by 38% (40.0 ± 9.5), and thickness by 45% (1.54 ± 0.30 mm) at 1 month; by 3 months, VAS was 20.0 ± 9.0 mm, WOMAC 25.0 ± 6.5, DASH 30.0 ± 7.5, thickness 1.40 ± 0.28 mm ( p  < 0.001). Saline reduced VAS by 30% (50.0 ± 14.0 mm), WOMAC by 26% (45.0 ± 9.5), DASH by 24% (50.0 ± 10.5), thickness by 30% (1.99 ± 0.38 mm) at 1 month; by 3 months, VAS was 40.0 ± 11.0 mm, WOMAC 40.0 ± 8.5, DASH 45.0 ± 9.5, thickness 1.85 ± 0.35 mm ( p  < 0.01). PRP outperformed saline ( p  < 0.001). Adverse events were mild (15% PRP, 7% saline). Conclusions Non-activated PRP induces time-specific growth factor release, outperforming saline in 3-month pain, function, and tendon thickness outcomes for tenosynovitis. The larger sample size enhances generalizability, aligning with recommendations for robust musculoskeletal trials and refuting claims of PRP equivalence to placebo. These findings guide PRP timing and support its efficacy over placebo. They also underscore the importance of individualized PRP dosing strategies based on platelet concentration thresholds. Trial registration In the Pan African Clinical Trials Registry (PACTR202506613254896) on 10 June 2025, and is accessible at: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=34788 .