The Influence Of Biodegradable Magnesium Interference Screw On Tendon-Bone Healing And Related Mechanism

Objective: Interference screw is widely used in the reconstruction of shoulder and knee joint ligaments after sports-related injury.At present,interference screws made of traditional metals and biodegradable polymers have several disadvantages due to the materials.Considering the desirable mechanical properties,biodegradablity and biocompatibility of Magnesium materials(Mg),we fabricated interference screws made of high-purity Mg and aimed to analyze the metallographic structure,mechanical properties,bioactivities in vitro.Furthermore,we investigated the influence of HP Mg interference screw on tendon-bone healing after ACL reconstruction and related mechanism.Methods: On basis of previous research,the processing of as-cast high purity(HP)Mg was optimized,and its microstructure and mechanical properties was tested.Interference screw made of HP Mg was designed and fabricated,and its extracts were prepared for the analysis of HP Mg influence on fibrochondrogenesis,in which the expression of fibrocartilage markers(Aggrecan,COL2A1 and SOX-9),BMP-2 and VEGF and the production of fibrocartilage matrix glycosaminoglycan(GAG)was tested.Then HP Mg screw was applied to fix the semitendinosus graft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium(Ti)screw as the control,The femur-tendon graft-tibia complex was retrieved at 3,6,9 and 12 weeks for X-ray scanning,ROM tests,gross observation,biomechanical tests,Micro CT scanning,histological and immunohistochemical analysis and in vivo fibrochondrogenesis induction assessment.Results:(1)The processed HP Mg had uniform and intensive microstructure,and its mechanical properties were greatly enhanced.(2)HP Mg interference screw was in slow corrosion in vitro.Its extracts improved the cell viability of human bone marrow-derived mesenchymal stem cells(h BMSCs),up-regulated expression of BMP-2,VEGF,fibrocartilage markers(Aggrecan,COL2A1 and SOX-9)and stimulated the production of fibrocartilage matrix.(3)Gross observation and range of motion(ROM)of the animal model reached normal levels at 12 weeks.No sign of host reaction was found in the X-ray scanning.The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL,and the ultimate load to failure and stiffness increased 12 weeks after surgery.In the histological analysis,the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery,whereas a disorganized fibrocartilage layer was found in the Ti group.In the immunohistochemical analysis and western blot assay,the expression of BMP-2,VEGF and the specific receptor for BMP-2(BMPR1A)was relatively high at the tendon-bone interface of the HP Mg group compared with the Ti group.Conclusion: Processed HP Mg interference screw demonstrated compact microstructure and high mechanical properties,and performed desirable bioactivities for fibrochondrogenesis.In the rabbit model of ACL reconstruction,HP Mg interference screw provided rigid mechanical strength and steady corrosion within the process of tendon-bone healing.Furthermore,the corrosion products of HP Mg interference screw promoted fibrocartilage tissues regeneration,which was critical for the biological fixation.The stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis.In present study,HP Mg interference screw performed great potential in the fixation of tendon graft.