Abstract
BACKGROUND: Recent studies have used the anterior cruciate ligament reconstruction (ACLR) mouse model to study the tendon-bone healing process. Although mechanical load has an important effect on ACL graft healing, only a limited number of studies have investigated the effect of treadmill exercise. PURPOSE/HYPOTHESIS: This study aimed to investigate the effects of different mechanical loading stimuli on the tendon-bone interface (TBI) healing process after ACLR in mice. It was hypothesized that moderate loading would positively affect TBI healing after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 58 C57BL/6 male mice (12 weeks old) underwent ACLR of the right knee. The first 30 mice were assigned to 5 exercise groups (n = 6 per group) to evaluate the different exercise regimens (study arm 1). After the optimal exercise regimen was identified, an additional 28 mice were included, and 14 mice in the exercise regimen were compared with 14 free cage controls (study arm 2). Starting 7 days after surgery, treadmill exercise was performed 5 days per week for 3 weeks. All animals were euthanized 4 weeks after surgery. Microfocus computed tomography (μCT) imaging, biomechanical testing, and histological tendon-bone tunnel healing (TBTH) scoring were performed. Statistical analyses were performed using the Wilcoxon signed rank test, the Mann-Whitney U test, and 1-way analysis of variance with a post hoc Tukey honestly significant difference test. Statistical significance was defined as P < .05. RESULTS: In study arm 1, no significant intergroup differences were observed in the μCT analysis (P = .18-.72) and histological assessment (P = .21). For study arm 2, the 10-m/min, 50-minute treadmill exercise was selected. Further μCT and biomechanical testing in study arm 2 revealed no significant intergroup differences. However, histological evaluation revealed significantly higher TBTH scores in the treadmill group as compared with the free cage activity group. This difference was most pronounced in the extra-articular region of the femoral tunnel (mean ± SD, 4.28 ± 2.15 vs 8.18 ± 2.98; P = .027) and the intra-articular region of the tibial tunnel (7.17 ± 7.07 vs 16.62 ± 5.42; P = .027). CONCLUSION: Our study demonstrated that moderate treadmill exercise after ACLR positively affects TBI healing in the femoral and tibial tunnels in the murine model. Future studies are necessary to objectively quantify the optimal type, magnitude, and duration of loading. CLINICAL RELEVANCE: There may be a role for a moderate-load rehabilitation protocol to improve healing of the tendon graft-bone interface in patients after ACLR.