TABLE 1.
A summary of the impact of inflammation on the outcomes of anterior cruciate ligament (ACL) graft healing.
| Study type | Causes of inflammation a /cells and factors involved | Results | References |
|---|---|---|---|
| Human | (1) | IL-6 levels were significantly higher in the group with <6 weeks of injury than in the group with >12 weeks since injury. IL-6 was significantly elevated in painful ligamentous injury of knee, showed negative correlation with Lysholm knee scores at 2 months, 6 months, and 1 year of follow-up, and showed negative correlation with Tegner level of sports activity at 1 year of follow-up | Gupta et al. (2021) |
| IL-6 | |||
| Human | (1) | High concentration of IL-6 and MMP-3 in the synovial fluid early post-ACL injury was associated with aberrant gait biomechanics in the injured limb at 6 months post-ACLR. | Evans-Pickett et al. (2021a) |
| IL-6, MMP-3 | |||
| Human | (1) | At 2 years of follow-up, patients that failed to reach the QOL PASS threshold after surgery (n = 6, 27%) had significantly greater IL-1α, IL-1ra, MMP-9 concentrations on the day of surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had significantly greater IL-1α | Lattermann et al. (2018) |
| IL-1α, IL-1ra, MMP-9 | |||
| Human | (1) (2) | Individuals with lesser biomechanical loading on the ACLR limb at the 6-month follow-up exam, compared with the contralateral limb, demonstrate greater concentrations of plasma MMP-3 and IL-6 early after ACL injury and during the early postoperative period | Pietrosimone et al. (2017) |
| MMP-3, IL-6 | |||
| Human | (2) | Patients with Remnant Preserved (RP)-ACLR had better knee stability within 3 months which was associated with higher expression of IL-8 in the synovial fluid compared with the patients with conventional ACLR | Kim et al. (2020) |
| IL-8 | |||
| Human | (2) | Graft loosening was closely related to increased gene and protein expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) within the first year of ACLR. There was a probable role of M1 but not M2 macrophages in the pathological process leading to graft loosening | Song et al. (2017) |
| IL-6, IL-8, TNF-α, M1 Macrophage | |||
| Human | (2) | Increased level of IL-10, IL-1β, IL-6, IFN-γ in the synovial fluid at 3–4 days post-ACLR was associated with a prolonged recovery | Inoue et al. (2016) |
| IL-10, IL-1β, IL-6, IFN-γ | |||
| Human | (2) | There is an association between tibial bone tunnel enlargement and elevated synovial fluid concentrations of IL-1β concentrations postoperatively after ACLR. A lower expression of IL-1β in the synovial fluid after autologous conditioned serum (ACS) treatment was associated with reduced tunnel widening 6 months and 1 year after ACLR. | Darabos et al. (2011a) |
| IL-1β | |||
| Human | (2) | An elevated synovial fluid concentration of IL-6, TNF-α, and NO at 7 days after ACLR was associated with tibial bone tunnel enlargement at 38 ± 7 weeks after surgery | Zysk et al. (2004) |
| TNF-α, IL-6, NO | |||
| Rat | (2) | The peri-tunnel bone loss correlated with high expression of MMP1, MMP13, and CD68+ cells at the graft–bone tunnel interface at week 6 after ACLR. | Lui et al. (2015) |
| MMP1, MMP13, CD68+ cells | |||
| Rat | (2) | Alendronate reduced peri-tunnel bone resorption, increased mineralized tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing at week 6, probably by reducing the expression of MMP1, MMP13, and CD68-positive cells | Lui et al. (2013a) |
| MMP1, MMP13, CD68+ cells | |||
| Rat | (2) | Macrophage depletion following ACLR significantly improved histological and biomechanical properties of the healing tendon–bone interface at 42 days | Hays et al. (2008) |
| Macrophages | |||
| Rat | (3) | Short-duration of low-magnitude cyclic axial loading of the ACL graft was associated with more inflammatory ED1 macrophages and less bone formation in the bone tunnel at 5, 14, 28 days post-ACLR. | Brophy et al. (2011) |
| ED1 macrophages | |||
| Rat | (3) | Interface width was smaller and collagen fiber continuity was greater in the immobilized group. Immobilized animals exhibited fewer ED1 + macrophages at the healing interface at 2 and 4 weeks. In contrast, there were more ED2 + macrophages at the interface in the immobilized group at 2 weeks | Dagher et al. (2009) |
| ED1macrophages | |||
| ED2 macrophages | |||
| Mice | (3) | A short period of immobilization after ACLR enhanced graft-to-bone tunnel healing by mitigating excessive MMP expression at day 30 | Nakagawa et al. (2019) |
| MMP -2, -3, -9, -13 |
Note. N.B.
a
Causes of inflammation: (1) ACL injury; (2) surgical trauma in ACLR, and (3) tendon graft-to-bone tunnel motion.