Synergistic Assembly Of Albumin And Lysozyme To Construct A Dual Function Central Venous Catheter With Anticoagulation And Antibacterial Properties

As medical technology enters a new era,central venous catheters have become an indispensable implantable device in clinical applications.However,it is often accompanied by the risk of complications such as venous thrombus embolism and catheter-related bloodstream infections,which not only make treatment more difficult,but also cause secondary injuries and financial losses to patients,and even endanger their lives.Therefore,central venous catheters should have excellent anticoagulant and antibacterial properties.Currently,its surface modification technology is widely studiedIn this paper,we address the above-mentioned issues,and based on the inherent structural and functional diversity of proteins,protein coatings may provide a unique biocompatible and sustainable platform for central venous catheters.Bovine serum albumin(BSA)is an inert protein with good hemocompatibility and resistance to nonspecific adhesion,and lysozyme(LZM)is a non-toxic antimicrobial protein widely found in nature.Therefore,in this paper,BSA/LZM coatings were constructed by controlling the molar ratios of BSA and LZM(4:0,3:1,2:2,1:3 and 0:4)and assembling them rapidly on the surface of the catheter under the oxidation of sodium persulphate(SPS).It oxidizes protein disulfide bonds to sulfonic acid groups,altering the protein secondary structure and exposing more hydrophobic groups and polar functional groups.Proteins assemble with each other under hydrophobic forces and electrostatic interactions to form protein nanoparticles and deposited by gravity to form a coating.The anti-adhesive properties of BSA and the antimicrobial properties of LZM are used to impart anticoagulant and antibacterial properties to the catheter surface.In this thesis,silicone rubber was chosen as the target for modification.Surface morphology,chemical composition and basic structural properties of the coatings were characterized by scanning electron microscopy,Fourier-transform infrared spectroscopy,Raman spectroscopy,X-ray photoelectron spectroscopy,ellipsometry and static water contact angle.The film formation and assembly mechanism were also explored using circular dichroism,dynamic particle size analysis,protein fluorescence labelling,thioflavin T fluorescence staining and 8-Anilino-1-naphthalenesulfonic Acid fluorescence staining.Hemolysis,cytotoxicity and expression levels of rabbit prothrombin fragment(F1+2)and rabbit platelet factor(PF4),rabbit C-reactive protein(CRP)and rabbit complement fragment 5a(C5a)to verify the biocompatibility of five different molar ratios of BSA/LZM coatings.The results showed that the haemolysis rate of all protein coatings was less than 5%,and that they were not cytotoxic and did not cause abnormal expression of F1+2,PF4,CRP and C5 a factors,confirming the good biocompatibility of the BSA/LZM protein coatings.Platelets,fibrinogen adhesion and activation and evaluation of their anticoagulant function in semi-in vivo animal studies.The results show that the 4:0,3:1 and 2:2 protein coatings have excellent anti-platelet adhesion and activation,and effectively prevent fibrinogen adhesion and activation.The excellent anticoagulant properties of the 4:0,3:1 and 2:2 samples were further confirmed by semi-in vivo animal experimentsBoth the colony count and bacterial liquid methods show excellent antibacterial activity in 2:2,1:3 and 0:4 samples,with the coating achieving over 95% antibacterial activity against E.coli and S.epidermidis.The anticoagulant and antibacterial properties of the 2:2 sample were significantly better than those of the other components by thermogram analysis.it does not stimulate coagulation,inflammatory factors or activation of the complement system,as demonstrated by simulated clinical in vivo blood factor tests,it also does not cause damage to liver or kidney function.In stability tests,the coating maintained relatively good anticoagulation and antimicrobial properties over a period of 15 days.this thesis uses BSA and LZM to construct an anticoagulant and antibacterial coating,not only to explore its film-forming mechanism,but also to verify its anticoagulant and antibacterial function for central veins.The technology offers a new way of thinking about surface modification of conduits and has potential applications.