Construction Of Hydrophobical Tannic Acid Coating And Their Antibacterial And Hemostatic Applications

Bacterial infection and massive bleeding after trauma have become serious threatens to human life and health.The performance of existing antibacterial and hemostatic materials/medical devices cannot meet the needs in clinical therapy.During the interactions between biomedical materials/devices and organisms to achieve the specific/designed functions,the structure/property of material surface normally play a key role.Therefore,for the development of new high-performance antibacterial and/or hemostatic devices,flexible coating materials have attracted much attention for the surface functionalization of existing biomedical devices,which can meet the needs in clinical therapy without changing their original medical functions/application scenarios.Moreover,there exist several challenges to be overcome for the exploitation of new medical coatings,including the facile modification process(easiness of large-scale production)and blood compatibility.Based on the above background,this paper intends to develop new coating materials with facile modification process/good blood compatibility through the hydrophobic modifications of tannic acid(TA),and to explore and optimize their antibacterial and hemostatic applications.In view of the problems of complex modification process and poor blood compatibility in the antibacterial functionalization of cationic compounds and polymers on the surface of medical materials / devices,in Chapter 2,one hydrophobic cationic TA derivative(AQTA)with the co-substitution of alkyl and quaternary ammonium groups were proposed for facile TA-based coatings.Thermoplastic polyurethane sheet(TPU)was selected as the model substrate of medical catheters to investigate the feasibility of AQTA coating for antibacterial functionalization of polymeric medical devices.Owing to its differed solubility in ethanol(soluble)and water(insoluble),AQTA coatings with tunable contents were deposited on TPU by facile one-step soaking process of ethanol solutions(different AQTA concentrations).Due to the existence of long-alkyl quaternary ammonium groups,AQTA exhibited high antibacterial properties against Escherichia coli and Staphylococcus aureus(S.aureus).On this basis,AQTA-coated TPU also displayed the excellent bactericidal effect against such two bacteria upon surface contact.In particular,the normal saline-soaking experiment confirmed the low leaching rate of AQTA coating on TPU,whilst leachates also possessed good blood compatibility and low cytotoxicity.Finally,the implantation-induced-infection model in mice demonstrated that AQTA-coated TPU can effectively control/avoid bacterial infection caused by implant pollution.In view of the uncertainty of the procoagulant properties of cationic compounds in hemostasis,in Chapter 3,three AQTA-coated AD(AD-A0.5,AD-A1 and AD-A2)with different coating contents were facilely prepared by soaking commercial medical alginate dressing(AD)in AQTA ethanol solutions(different/low concentrations of 0.5,1,2 mg/m L).The leachates of all three AD-As displayed low hemolysis and high cell compatibility.In vitro experiments show that AD-A1 with optimal/medium coating content exhibited better hemostatic property than AD,the mechanism of which is the improved platelet adhesion by cationic coating.Two typical rat-hemorrhage models further confirmed the better hemostatic performance of AD-A1 than AD.There also existed also some interesting findings on the procoagulant functionalization of cationic AQTA coating: 1)AD-A0.5 and AD-A2 with lower/higher coating content(than AD-A1)did not improve the hemostatic property of negatively charged AD;2)AQTA-coated medical gauze(G,also negatively charged)also realized the improved hemostatic property/platelet adhesion by the medium/moderate coating content;3)however,in vitro results of AQTA-coated(cationic)chitosan dressing(CS)demonstrated that cationic coating played an obvious negative effect on the platelet adhesion/hemostatic property of CS.Considering together the distinct surface structures of three dressings and their in vitro results,the rational design and optimization of cationic coatings for procoagulant functionalization can be preliminarily revealed;that is,it is necessary to consider together the positive charges of coating(as well as its content)and the original surface structure of dressing(i.e.different interactions of positively/negatively surfaces with plasma proteins)in order to construct the optimal surface for platelet adhesion and the resultant high hemostatic property.Chapter 3 revealed the shortcomings of cationic AQTA coating for procoagulant functionalization,including the precise control of coating content and the limitations on the pristine surface of biomedical materials/devices.In Chapter 4,one hydrophobic tannic acid derivate(ATA)was constructed as a universal procoagulant coating by the single substitution tannic acid with hydrophobic alkyl chains.Soaking medical gauze in ATA ethanol solution(at high concentration of 8 mg/m L)can transfer hydrophilic G into G-ATA8 with strongly hydrophobic surface(water contact angle of 130°).Due to the hydrophobic surface endowed by ATA coating,G-ATA8 not only exhibited better in vitro hemostatic property than G(the main mechanism is the improved platelet adhesion by ATA),but also inhibited bacterial adhesion and displayed excellent hemostatic performance in rat & rabbit femoral-artery-injury models.In particular,the in vitro/in vivo hemostatic performance of unmodified CS —— which initially possessed strongly hydrophobic surface —— can also be improved by the high content of ATA coating.On this basis,ATA coating was further applied to the surface modification of self-made gelatin sponge particles(crushed from medical sponge,GSP).ATA coating improved the hemostatic performance of GSP under both dry-state and wet-state application scenarios(through the improved platelet adhesion): the former indicated the better performance in rat femoral-artery-injury model,and the latter referred to the improved embolization effect of renal artery embolization effect in coagulation-dysfunction rabbit model(which is a typical clinical application of wet GSP).In sum,two hydrophobic coatings have been constructed by the hydrophobic modification of tannic acid,both of which can be deposited on polymer medical materials by facile one-step soaking process of ethanol solutions and possess the advantages of easy adjustment of coating content.A series of promising biomedical materials/devices with excellent antibacterial and hemostatic performances have also been developed by exploring and optimizing the antibacterial/procoagulant functionalization of such two hydrophobic coatings on versatile biomedical materials.