Study Of Antibacterial And Anticoagulant Dual-functional Coating By Co-immobilization Of HA And Cu~Ⅱ

Thrombosis and infections are the two major clinical complications of the using of blood-contacting biomaterials and indwelling medical devices.Drug therapies using anticoagulant drugs(e.g.,heparin)and antibiotics are common clinical measures to solve these two complications.However,such a co-administration of drugs is usually associated with a series of adverse reactions,including the risk of heparin-induced thrombocytopenia,hemorrhage and the side effects associated with antibiotic abuse.Biomolecule grafting is an effective method for surface functionalization of biomaterials.However,the existing antibacterial and anticoagulant bifunctional modification methods usually involve complex processes,such as complex surface pretreatment of materials and multi-step anchoring of functional molecules to coatings.Therefore,it is indispensable and urgent to develop a simple,efficient and versatile method to modify the surface of blood-contacting biomaterials.Endothelium glycocalyx is a barrier to maintain vascular wall permeability and is a dynamic,multifunctional surface that inhibits the adhesion of leukocytes,platelets,erythrocytes and bacteria to endothelial cells while continuously contacting the flowing blood.NO released from endothelium has the biological functions of inhibiting platelet aggregation,activation and anti-inflammatory,etc.Herein,we biomimetically modified the surface of blood-contacting materials,we proposed an endothelium-inspired dual-functional coating with synergistic anticoagulation and antibacterial properties by covalently co-immobilization of an antifouling agent,HA and a Cu~Ⅱ chelated complex,Cu~Ⅱ-DOTA on an amine-rich surface(PADA)that prepared by poly(allylamine)(PAa)modified poly(dopamine)(PDA)by Schiff base reaction and Michael addition.HA and Cu ~Ⅱ exert a synergistic effect on antibacterial and anticoagulant properties,imparting a highly biomimetic function to the blood-contacting material.The successful preparation of PADA coating and HA/Cu~Ⅱ-DOTA coating were confirmed by some material characterization methods such as ATR-FTIR,XPS,UV-VS,water contact angle and acid orange amine group quantification;The results of NO catalytic release rate And NO release stability indecated the stable and continuous NO in-situ catalytic function of the HA/Cu~Ⅱ-DOTA coating;the results of antibacterial experiment showed the synergistic effect of HA and Cu~Ⅱ-DOTA on antibacterial property,1:3 have the best antibacterial properties and excellent antibacterial stability;The adhesion activation of fibrinogen and platelets,the ex-vivo thrombogenicity tests verified that 1:3 coating can significantly inhibit thrombosis.We anticipate that the dual-functional HA/Cu~Ⅱ-DOTA coating strategy would be a milestone in the development of surface engineering,especially to that of blood-contacting biomedical devices.