Antibacterial Effect And Safety Evaluation Of Composite Coating Used In Artificial Knee Replacement

Background and objectiveKnee arthroplasty is one of the most common surgical procedures in artificial joint replacement,which is the only effective treatment for various knee joint diseases in late period.Clinical practice has proved that most patients can obtain higher satisfaction after joint replacement.However,as the number of surgical procedures increase and the time extended,the incidence of complications and adverse reactions also gradually increased.Infection is one of the most common and serious consequences of knee arthroplasty.Most of the antibiotics loaded on the surface of artificial prosthesis can get better antibacterial effect,but also increase the incidence of drug resistance.In this study,anodic oxidation and electrode position method was used for preparing Ag-loaded TiO2 Nanotube.A series of in vitro and in vivo experiments were carried out to evaluate its characterization,the release rate of silver ions,biocompatibility and antibacterial effect,which will provides theoretical basis and experimental basis for future application in clinical knee replacement.Method1.TiO2 nanotubes were prepared on the surface of pure titanium by anodic oxidation and Nano-silver particles were loaded on the nanotubes by electrodeposited;the coating surface morphology,release rate of silver ion prepared by different silver nitrate solution and antibacterial activity on floating and attached Staphylococcus aureus and Escherichia coli in vitro.2.Observe the effect of Nano-silver titania nanotubes on the biological behavior of osteoblasts in vitro.3.After knee arthroplasty,a series experiments were designed to observe the biocompatibility of the implanted prosthesis.4.Staphylococcus aureus was injected into the joint cavity to establish knee joint replacement infection model,and then the general condition of the rabbits such as mental state,respiration,heart rate,food intake and excretion and the appearance of joints was observed.The changes of body temperature were recorded,bacterial culture of synovial fluid was carried out,the C-reactive protein and inflammatory cytokines TNF-α,IL-6 and IL-1 in each group were measured to evaluate the antibacterial activity of titania nanotubes loaded with different concentrations of nano-silver.Results1.The surface of TiO2 nanotubes was smooth,while nanotubes prepared under 20 V was more orderly.2.To a certain extent,Ag in low and medium concentration can promote the proliferation of osteoblasts,while high concentrations of Ag have obvious toxic effects on osteoblasts and cell proliferation was inhibited.Silver ion release rate of Ag-loaded TiO2 nanotube was the highest at the first day and then gradually decreased until 2-3 weeks to achieve a relative balance.Sterilization rates of TiO2 nanotubes to floating and attached Staphylococcus aureus and Escherichia coli were 15-20%.Sterilization rates of silver-loaded TiO2 nanotubes showed a significant dose-dependent relationship with the Ag ion concentration at the same time point(P all<0.05).3.No skin irritation and no heat source existed in Ag-loaded TiO2 nanotubes.No death occurred within 24 hr and no obvious acute toxicity.4.The colonies of S.aureus were cultured in synovial fluid on the blood plate in each group.The colony density of the three Ag-loaded TiO2 nanotubes groups were significantly lower than that of PT and NT group(p<0.05).The levels of C-reactive protein in NAg-L group,NAg-M group and NAg-H group were significantly lower than those in PT and NT group(p<0.05).The levels of TNF-α,IL-1β and IL-6 in NAg-L,NAg-M and NAg-H groups were significantly lower than those in PT group and NT group on the 3rd,7th and 14th day after infection with S.aureus(P<0.05).Conclusions:Nano silver titania nanotubes has a better silver ion release properties and showed a showed good biocompatibility and antibacterial activity both in vitro and in vivo.It has a certain impact on the biological behavior of osteoblasts with the increase of silver ion concentration.Strict control of silver ion concentration allows it to exert antimicrobial activity while minimizing the toxic effects on osteoblasts.To sum up,as a new type of artificial prosthesis antibacterial coating,nano-silver nanotubes loaded nanotubes has a good prospect.