Study On Materials Design And Biological Functions Of Novel Biodegradable Magnesium Alloys For Orthopaedic Implants Applications

Magnesium alloys are promising novel biodegradable(absorption)materials as orthopaedic implants because of their good biocompatibility,satisfactory mechanical properties which can match with the bone as well as their biodegradability in human bodies.Currently the orthopaedic research of the biodegradable magnesium alloys mainly focus on their mechanical properties,degradation behaviors,biocompatibility,etc.However,there are rare reports on the clinical medical function and design of magnesium alloys.This paper aims to find some trace alloying elements with specific biomedical functions when added to the magnesium and to develop the novel biodegradable magnesium alloys.Aside from the requirements of biological safety and mechanical support after implantation,with both the alkaline environment and continuous release of alloy element ions arose from their natural degradation,the novel biodegradable magnesium alloys would also exhibit multiple biomedical functions,such as osteogenesis,angiogenesis and antibacterial activities,etc.The research results in this study will provide theory bases and experimental proof for the development of novel biodegradable magnesium alloys and their clinical applications.In this study,two kinds of novel biodegradable magnesium alloys(Mg-Sr alloys,Mg-Cu alloys)were systematically and deeply investigated,and many meaningful conclusions have been reached.Strontium(Sr)is known to promote bone growth and bone formation,therefore appropriate amounts of Sr were added into the magnesium matrix in order to develop a novel class of biodegradable Mg-Sr binary alloys(Mg-0,25Sr,Mg-1.0Sr,Mg-1,5 Sr,Mg-2.5Sr).Effects of Sr on the microstructures,mechanical properties and corrosion resistance of as-casted,as-annealed and as-extruded Mg-Sr alloys were investigated.It was found that the microstructures of Mg-Sr alloys consisted of a-Mg matrix and Mg17Sr2 second phases.Sr existed mainly in the form of second phase due to its relatively low solid solubility in the magnesium matrix.For as-casted Mg-Sr alloys,some second-phase particles were observed within the grains and others were distributed along the grain boundaries.After extrusion,Mg-Sr alloys presented much finer grain size and smaller second-phase particles.The mechanical properties of as-extruded Mg-Sr alloys promoted greatly compared with that of as-casted Mg-Sr alloys.The compressive strength of the alloys matched with that of human cortical bone preferably,and it increased first and then decreased with the addition of Sr(Mg-1.5Sr reached maximum).The corrosion resistance of as-casted Mg-Sr alloys rose first and then fell with the increase of the Sr content,and the degradation rate of Mg-1.5Sr was the lowest.By contrast,the corrosion resistance of as-extruded Mg-Sr alloys was improved significantly.As-extruded Mg-Sr alloys were selected for further studies due to their excellent mechanical properties and corrosion resistance.Hemolysis test,cytotoxicity evaluation,cytoskeleton and live-dead cell dyeing,alkaline phosphatase activity detection,extracellular matrix mineralization detection,collagen protein detection,endothelial cell migration assay,in vitro three-dimensional vascularization forming experiment,aortic ring model of angiogenesis assay,osteogenesis-related and angiogenesis-related gene expressions experiments,and antimicrobial assay were carried out to systematically and comprehensively investigate the biological safety and specific biomedical functions of Mg-Sr alloys.The results indicated that as-extruded Mg-Sr alloys had no hemolytic potential and possessed good cell biocompatibility.In the aspect of biological functionalization,as-extruded Mg-Sr alloys obviously promoted the adhesion,proliferation and differentiation of MC3T3-E1 cells and could regulate the osteogenesis-related gene expression,especially Mg-1.0Sr and Mg-1.5Sr.Meanwhile,as-extruded Mg-Sr alloys promoted the proliferation and migration of human vascular endothelial cells(HUVEC)and the formation of capillary network.Angiogenesis-related gene expression was regulated by Mg-Sr alloys as well.Moreover,as-extruded Mg-Sr alloys showed strong anti-infective function against the orthopaedic common bacteria Staphylococcus aureus(S.aureus)owing to the rapid increase of pH value of the bacterial suspension during their degradations.All the above experimental results showed that as-extruded Mg-Sr alloys had excellent osteogenic function,angiogenic function,and antibacterial performance at the same time.In the physiological environment,the high alkalinity caused by the degradation of magnesium alloys would be buffered via the homeostasis system which makes in vivo environment around the implants tend to be neutral.As a result,the alkaline antibacterial effect would be weakened even be eliminated.Copper(Cu)has been proved to have strong antibacterial effect and be beneficial to biological functions in human bodies.Therefore,a series of biodegradable Mg-Cu alloys(Mg-0.03Cu,Mg-0.19Cu,Mg-0.57Cu)are designed and fabricated in the hope that the alkaline environment combined with the release of Cu ion would endow the Mg-Cu alloys with prolonged antibacterial effects.Effects of Cu content variation on the microstructures,mechanical properties and corrosion resistance of as-casted Mg-Cu alloys were investigated.It was found that the microstructures of Mg-Cu alloys consisted of the ?-Mg matrix and Mg2Cu second phases.With the increase of the Cu content,there was no observable difference in the average grain sizes among the various Mg-Cu alloys,but an increase in the amount of second phase particles.The mechanical properties of as-casted Mg-Cu alloys could meet the requirements as orthopaedic materials in the early implanting stage with the dispersion strengthening effect of Mg2Cu second phases.The as-casted Mg-Cu alloys could degrade in simulated body fluid at a degradation rate higher than that of the as-casted pure Mg.The increase in the amount of Mg2Cu with Cu content,accelerated the degradation of Mg-Cu alloys in the physiological environment due to its promoting effect on the galvanic corrosion.It should be noted that Mg ions and Cu ions continuously released during the degradation process of Mg-Cu alloys and their rates of release were within the scope of the biological safety.The hemolysis and cytotoxicity test results indicated that Mg-Cu alloys had favorable hemocompatibility and cytocompatibility.The antibacterial experiment showed that the alkaline environment combined with Cu release endowed the Mg-Cu alloys with dual antibacterial effects.In addition,the low content of Cu addition could endow the magnesium alloys with the osteogenesis and angiogenesis functions.