Construction Of Antibacterial And Anticoagulant Functional Coatings Based On Metal-Phenol (Amine) Chemistry

As a kind of medical device,central venous catheter is widely used in clinical practice,playing an important role in continuous drug delivery.However,central venous catheters have been facing the risk of complications such as postoperative infection and thromboembolism in clinical practice.During the use of a central venous catheter,thrombus and colonization of bacterial colonies may form on the surface of the catheter,resulting in serious catheter embolism and catheter-related systemic infections.Clinically,anticoagulant drugs and antibiotics are usually used to prevent and treat embolism and infection on the surface of the catheter.Yet anticoagulant drugs may cause complications such as systemic bleeding,and antibiotics also face the risk of resistance.Therefore,endowing the catheter with antibacterial and anticoagulant function is of great significance for reducing the incidence of central venous catheter-related complications.This paper proposes a catheter surface modification strategy to solve the problem of complications faced by central venous catheters in clinical applications.In view of the catechol structure of the dopamine(DA)molecule has the following properties:1)Adhesion ability.2)Can coordinate with copper ions.3)Can react with Hexamethylene diamine(HD)in two phenolamine chemical reactions,a layer of Cu~Ⅱ@DA/HD coating is constructed on the surface of the medical catheter.By grafting poly N-isopropylacrylamide(PNIPAm),a kind of polymer,on the amino group on the surface of the Cu~Ⅱ@DA/HD coating,the Cu~Ⅱ@DA/HD-PNIPAm coating was prepared.The copper ions in the Cu~Ⅱ@DA/HD-PNIPAm coating endow its antibacterial function,and can catalyze endogenous L-reduced glutathione(GSH)to reduce endogenous nitrosothiol(RSNO),thereby producing nitric oxide(NO)gas that can inhibit platelet activation and aggregation.The PNIPAm grafted on the surface of Cu~Ⅱ@DA/HD-PNIPAm coating can change its conformation in response to changes in temperature,thus eluting bacteria adhering to the coating surface to achieve the inhibition of bacterial adhesion.As it endues the catheter antibacterial,anticoagulant and antibacterial-adhesion functions,the Cu~Ⅱ@DA/HD-PNIPAm coating is expected to solve the complications such as postoperative infection and thromboembolism faced by central venous catheters.In this research,X-ray photoelectron spectroscopy(XPS),reflection attenuation Fourier infrared transform spectroscopy(RA-FTIR),electron paramagnetic resonance(EPR),mass spectrometry(MS)and other material characterization methods were used to prove that the Cu~Ⅱ@DA/HD-PNIPAm coating had been successfully constructed on the surface of the catheter;the water contact angle of Cu~Ⅱ@DA/HD-PNIPAm coating was measured at different temperatures,which proved that temperature can change the hydrophilicity and hydrophobicity of Cu~Ⅱ@DA/HD-PNIPAm coating surface;Real-time detection of the catalytic NO release rate proved that Cu~Ⅱ@DA/HD-PNIPAm coating can stably release NO,in addition,it screened out an ideal preparation process which making the catalytic NO release rate of Cu~Ⅱ@DA/HD-PNIPAm coating close to that of natural endothelium.Some other characterization methods,consist of hemolysis experiment,cytotoxicity experiment,platelet adhesion and activation experiment both with rabbit complement fragment 5a(C5a),rabbit C-reactive protein(CRP),rabbit platelet factor 4(PF4)and rabbit prothrombin fragment F1+2(F1+2)were used as biochemical characterizations,those factor expression level experiment verify the biocompatibility of Cu~Ⅱ@DA/HD-PNIPAm coating.The results show that the hemolysis rate of Cu~Ⅱ@DA/HD-PNIPAm coating is less than 5%,and there is no obvious cytotoxicity;behaviors that the coating can inhibit platelet adhesion and activation on its surface without causing the abnormal expression of factors such as CRP,C5a,PF4 and F1+2 prove that Cu~Ⅱ@DA/HD-PNIPAm coating has good biocompatibility.The excellent anticoagulant function of Cu~Ⅱ@DA/HD-PNIPAm coating was also proved through semi-in vivo animal experiment.The antibacterial experiment results of the colony counting method prove the excellent antibacterial function of the Cu~Ⅱ@DA/HD-PNIPAm coating,and the antibacterial rate of the coating against E.coli and S.epidermids can reach more than 90%;the results of the bacterial adhesion experiment prove Cu~Ⅱ@DA/HD-PNIPAm coating can inhibit the adhesion of bacteria on the surface of the coating by changing the temperature,and the inhibition rate of bacteria adhesion exceeds 80%.