The Biodegradation Behavior And Biocompatibility Of Calcium Phosphate Coated Mg-Nd-Zn-Zr Alloy For Orthopedic Applications

Magnesium and its alloys exhibit high mechanical strength and good biocompatibility,and their modulus is similar to natural cortical bone,which could help to avoid the stress shielding effect.These advantages make them promising candidates for bone repair applications.However,the present Mg-based alloys always exhibit excessive corrosion rates and local corrosion behavior,which have become the main obstacles for their clinical applications.Our group has developed a novel biodegradable Mg alloy Mg-Nd-Zn-Zr series（Jiao Da Bio-Mg,denoted as JDBM alloy）.The previous studies show that JDBM alloy exhibits slow and uniform corrosion,which is much slower than that of the most studied WE43 alloy.However,the corrosion rate is still higher than desirable especially in the early stage,and the hemolysis ratio cannot meet the present constraints developed for traditional biomaterials like stainless steel and Ti alloys.In this work we firstly investigate the biodegradation mechanism of JDBM alloy,by studying the effects of osteoblasts and flowing solution on the corrosion behaviors.In order to further reduce the corrosion rate and improve the biocompatibility for orthopedic application,we develop a calcium phosphate coating（brushite,CaHPO₄·2H₂O,hereinafter refered to as DCPD）with high bonding force on JDBM alloy by chemical conversion method.The in vitro corrosion behavior and biocompatibility are studied correspondingly.At last,three types of bone fracture models are designed with rabbits and goats,respectively,and DCPD coated JDBM implants are used as fracture fixation devices.The in vivo degradation,the safety and efficacy are studied systematically.The main conclusions are listed as follows.Cells existing and solution flow could influence the corrosion behavior of Mg alloys.Osteoblasts were seeded on JDBM samples,and it is found that the corrosion layer underneath the osteoblasts become thinner,indicating a reduced corrosion rate.Osteoblasts could regulate and control Ca element distribution,and induce calcium phosphate depositing in the corrosion layer,which is supposed to make the corrosion layer denser,and thus protect Mg substrate.The corrosion rates of pure Mg and JDBM alloy increase with the flow speed.This is probably because the flowing solution accelerates the dissolving of the corrosion layer,and weakens its protection.The corrosion of JDBM is not so sensitive to flow speed as pure Mg,probably because the presence of Nd,Zn and Zr in JDBM alloy makes the corrosion layer denser and more stable.The pH value shows no obvious change owing to the pH buffering systems HCO₃^-/CO₃^2-and H₂PO₄^-/HPO₄^2-.While the osmolality also shows no correlation with corrosion rates and flow speed,which is controlled by two factors:the Mg ion release during degradation,and ion deposition in corrosion layer.DCPD coating could improve the corrosion resistance as well as the biocompatibilityof JDBM alloy.We developed the DCPD coating by a chemical convertion method with a thickness of 15-20μm,which shows high bonding strength and hydrophilicity.After DCPD coating treatment,the corrosion rate of JDBM alloy in Hank‘s solution decreases from 0.54 mm·year^-1 to 0.39 mm·year^-1.The corrosion resistance is greatly improved,especially in the early stage.After 10 days immersion,residual DCPD is still found on the samples.The electrochemical test also shows that the DCPD coating could improve the corrosion potential and reduce the corrosion current,which indicates a slower corrosion reaction.JDBM-DCPD shows a hemolysis rate of 0.68%,which is much lower than that of JDBM（48%）.DCPD coating shows no cytotoxicity,and could induce osteoblasts adhesion,proliferation.It also increases the alkaline phosphatase（ALP）level,and promotes Collagen I secretion and biomineralization.Therefore,JDBM-DCPD shows good biocompatibility and osteoinductivity.At last,JDBM-DCPD screws and plates were implanted in the tibia and mandible of rabbits and femoral condyle of goats respectively,to evaluate their in vivo degradation behavior,biosafety and efficacy as bone fracture fixation devices.During the anamial experiments,JDBM-DCPD implants show good biosafety and biocompatibility.No obvious inflammation is observed,and the functions of the main organs are not disturbed.The serum Mg²⁺level shows no obvious increase after implantation.The implants could induce new bone formation.The DCPD coating could prolong the degradation timeline of JDBM implants for at least 10 weeks in rabbit tibias.At 4 months postoperation,the bending strengths of WE43,JDBM and JDBM-DCPD plates are reduced by 63%,48%and 30%,respectively.After implanted in rabbit mandible,the volume of JDBM-DCPD screws decreases gradually with time,and only 10.7 vol.%of the original implants remains at 18 months.According to the existing data,the complete degradation time is extrapolated to be 22²3 months,which is appropriate for mandible repair.The degradation products of the screw include two layers.The inner layer is mainly composed of C and O which has many nano-sized pores,while the outer layer consists of more Ca and P,and has similar composition with peri-implant new bone tissue.After 18 months in goat femoral condyle,the volume of JDBM-DCPD screws only reduces by¹0%,indicating the degradation rate is lower than desirable.In future,the degradation rate could be further adjusted to an appropaite range by decreasing the thickness of the coating layer.