Magnesium (Mg) based interference screws developed for promoting tendon graft incorporation in bone tunnel in rabbits

How to enhance tendon graft incorporation into bone tunnels for achieving satisfactory healing outcomes in patients with anterior cruciate ligament reconstruction (ACLR) is one of the most challenging clinical problems in orthopaedic sports medicine. Several studies have recently reported the beneficial effects of Mg implants in bone fracture healing, indicating the use potential of Mg devices in promoting the tendon graft osteointegration. Here, we developed an innovative Mg-based interference screws for fixation of the tendon graft in rabbits underwent ACLR and investigated the biological role of Mg-based implants in the graft healing. The titanium (Ti) interference screw was used as the control. We demonstrated that Mg interference screw significantly accelerated the incorporation of the tendon graft into bone tunnels via multiscale analytical methods including scanning electronic microscopy/energy dispersive spectrometer (SEM/EDS), micro-hardness, micro-Fourier transform infrared spectroscopy (μFTIR), and histology. Our in vivo study showed that Mg implants enhanced the recruitment of bone marrow stromal stem cells (BMSCs) towards peri-implant bone tissue, which may be ascribed to the upregulation of local TGF-β1 and PDGF-BB. Besides, the in vitro study revealed that higher Mg ions was beneficial to the improvement of capability in cell adhesion and osteogenic differentiation of BMSCs. Thus, the enhancement in cell migration, cell adhesion and osteogenic differentiation of BMSCs may contribute to an improved tendon graft osteointegration in the Mg group. Our findings in this work may further facilitate clinical applications of Mg-based interference screws for enhancing tendon graft-bone junction healing in patients indicated for ACLR. How to promote tendon-bone junction healing is one of the major challenging issues for satisfactory clinical outcomes in patients after ACL reconstruction. The improvement of bony ingrowth into the tendon graft-bone interface can enhance the tendon graft osteointegration. In this study, we applied Mg based interference screws to fix the tendon graft in rabbits and found the use of Mg screws could accelerate and significantly increase mineralized matrix formation at the tendon-bone interface in animals when compared to those with Ti screws. We elucidated the mechanism behind the favorable effects of Mg screws on the graft healing in both in vitro and in vivo studies from multiscale technologies. The optimized interface structure and function in Mg group may be ascribed to the improved cell migration capability, enhanced cell adhesion strength and promoted osteogenic differentiation ability of BMSCs under the stimuli of Mg ions degraded from implanted Mg screws. Our findings may help us broaden our thinking in the application potential of Mg interference screws in future clinical trials.