Magnesium inference screw supports early graft incorporation with inhibition of graft degradation in anterior cruciate ligament reconstruction

Abstract

Patients after anterior cruciate ligament (ACL) reconstruction surgery commonly encounters graft failure in the initial phase of rehabilitation. The inhibition of graft degradation is crucial for the successful reconstruction of the ACL. Here, we used biodegradable high-purity magnesium (HP Mg) screws in the rabbit model of ACL reconstruction with titanium (Ti) screws as a control and analyzed the graft degradation and screw corrosion using direct pull-out tests, microCT scanning, and histological and immunohistochemical staining. The most noteworthy finding was that tendon graft fixed by HP Mg screws exhibited biomechanical properties substantially superior to that by Ti screws and the relative area of collagen fiber at the tendon-bone interface was much larger in the Mg group, when severe graft degradation was identified in the histological analysis at 3 weeks. Semi-quantitative immunohistochemical results further elucidated that the MMP-13 expression significantly decreased surrounding HP Mg screws with relatively higher Collagen II expression. And HP Mg screws exhibited uniform corrosion behavior without displacement or loosening in the femoral tunnel. Therefore, our results demonstrated that Mg screw inhibited graft degradation and improved biomechanical properties of tendon graft during the early phase of graft healing and highlighted its potential in ACL reconstruction.

In vivo evaluation of Mg–6Zn and titanium alloys on collagen metabolism in the healing of intestinal anastomosis

“…As being a key component of the ribosomal machinery that translates genetic information encoded by mRNA into polypeptide structures, we hypothesized that relatively high concentrations of magnesium could enhance the protein translation for the extracellular matrix such as collagens I and III 12 . Results of our study were consistent with various other research findings 39 40 41 . A variety of cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) play an important role in the expression of MMPs 42 43 .…”

“…As magnesium could inhibit intracellular calcium influx, reduces mitochondrial calcium overload, and conserves intracellular adenosine triphosphate (ATP) as ionized Mg-ATP, we hypothesized that increased extracellular magnesium may have a protective effect by decreasing the secretion of interleukins during ischemia in the anastomotic healing. In another frontier study, the researchers hypothesized that Mg ion released from corroded Mg screws blocked MMP-13 expression, inhibited the degradation of collagens via tyrosine kinase inhibitors through a highlighted signaling pathway 41 . In previous researches, it was demonstrated that extracellular Mg reduced MMPs in a dose-dependent manner in cultured rat vascular smooth muscle cells as well as rat cardiac fibroblasts potentially via two tyrosine kinase inhibitors, genistein and herbimycin A 44 45 .…”

Biodegradable Magnesium Screws Accelerate Fibrous Tissue Mineralization at the Tendon-Bone Insertion in Anterior Cruciate Ligament Reconstruction Model of Rabbit

“…has also recently used Mg interference screws to fix tendon graft into bone tunnels in a rabbit model of ACL reconstruction26. Although our animal model is similar to Cheng’s model, the research interests of Cheng PF’s and our studies are different.…”

“…Cheng et al . also found that Mg interference screws could effectively inhibit the degeneration of the tendon graft during the remodeling phase via reducing the expression level of MMP-13, indicating that more collagen fibers in the tendon graft were preserved to connect the surrounding bone tissue for higher knee stability26. However, it is still unclear if Mg based fixators can also promote graft healing at the mid-tunnel interface as spatial differences in tendon-bone healing in a bone tunnel was reported27.…”

Translational status of biomedical Mg devices in China

“…Interference screws are used to fix tendon graft with a bone tunnel in anterior cruciate ligament (ACL) construction. Cheng et al [32] reported that the high-purity magnesium (HP–Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1, and SOX-9), and glycosaminoglycan (GAG) production in vitro cell culture tests. Then they used the HP-Mg interference screw to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium screw as the control.…”