Effect of mesenchymal stem cell-Derived secretome injection on functional outcomes after anterior cruciate ligament reconstruction using peroneus longus tendon autograft: a double-blind randomized controlled trial

Introduction : Graft healing after anterior cruciate ligament (ACL) reconstruction remains challenging, as inadequate ligamentization and tendon–bone integration can lead to graft failure. Mesenchymal stem cell (MSC)-derived secretome, a cell-free conditioned medium containing bioactive factors, has demonstrated promising regenerative potential in preclinical studies. This study compared six-month functional outcomes of ACL reconstruction using a peroneus longus tendon (PLT) autograft with and without adjuvant secretome injection. Methods : A double-blind randomized controlled trial enrolled 24 participants undergoing arthroscopic single-bundle ACL reconstruction with a PLT autograft, randomly assigned to receive intralesional secretome injection into the graft (secretome group, n = 12) or saline placebo (control group, n = 12). Functional outcomes were assessed preoperatively and at six months using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form and Tegner–Lysholm Knee Scoring Scale. Between-group comparisons used the independent-samples t-test or Mann–Whitney U test, with significance at p < 0.05. Results : Baseline IKDC scores were comparable (secretome 48.57 ± 4.91 vs. control 47.51 ± 4.45; p > 0.05). At six months, the secretome group showed significantly higher IKDC scores (86.89 ± 5.11 vs. 78.27 ± 3.91; p < 0.01) and Tegner–Lysholm scores (87.08 ± 5.16 vs. 79.33 ± 2.67; p < 0.01). No major adverse events occurred; transient swelling and mild pain resolved spontaneously. Conclusion : In this small randomized controlled trial, adjunctive MSC-derived secretome administration during ACL reconstruction with a peroneus longus tendon autograft was associated with higher six-month patient-reported knee function scores compared with placebo. Level of evidence Level 1. Registry: ClinicalTrials.gov, NCT07723625, Registration date: 19 July 2026.