Systematic Construction And Investigation Of Carbon Nanotubes/Mesoporous Silica Functional Composite Coatings For Cardiovascular Stents

Coronary artery disease(CAD)continues to be one of the leading causes of death in the world.Angioplasty with cardiovascular stents is the most important method for the treatment of CAD.However,the drug-eluting stents(DES)that are widely used have the increased risks of inflammatory reactions,delayed re-endothelialization and late stent thrombosis(LST)because of the persistence of the polymer coatings.To improve the biosafety,a series of novel inorganic functional coatings were constructed in this thesis by employing mesoporous silica(MS)as a porous drug carrier,and carbon nanotubes(CNTs)as a flexible reinforcing element.The related functions including mechanical property,drug-loading and release performance,blood compatibility,and endothelialization process were systematically investigated in relation to the component,structure and surface modification of these designed coatings.In chapter 2,coatings on 316L stainless steels(316L)with similar topographies and different wettabilities were obtained through sol-gel process by regulating the proportions of tetraethoxysilane(TEOS)and methyltriethoxysilane(MTES).Vascular endothelial cells(EC)and smooth muscle cells(SMC)responded differently to the coated surfaces.Enhanced endothelialization of bare 316L was found at the moderately hydrophilic coating(contact angle 45.3°)which exhibited effective inhibition of SMC and negligible influence on EC.Based on this result,magnetic mesoporous silica nanoparticles(MMSNs)were incorporated into this coating for carrying drugs.However,a serious shedding was observed after stent expansion due to the brittleness of this coating,and the loading capacity of rapamycin(RAPA)was as low as 9.64±1.36?g/mg,which can not satisfy the practical applications.In chapter 3,the electrophoretic deposition(EPD)method was utilized to explore the possibility of constructing CNTs@MMSNs/CNTs composite coatings on stents.A crack-free two-layered coating with impressive network nanotopology was obtained by regulating the composition and structures.That is,a thin CNTs film acted as an inner buffer layer,and a second MMSNs/CNTs composite coating acted as a functional layer.The mechanism of the CO-EPD process of MMSNs and CNTs was proposed,in which the addition of Mg²⁺played an important role.Moreover,the excellent mechanical flexibility and blood compatibility of this polymer-free coating were exhibited in vitro,the RAPA-loading capability was 60.10±2.43?g/mg,and the drugs could be continuously released to 14 days.Finally,the in vivo study showed that this nanostructured DES had obvious advantages of rapid re-endotheliazation in the early stage when compared with the commercial polymer coated DES(P-FBII DES),which was of great importance to reduce the risks of LST.In chapter 4,a coaxial composite nanofiber of SWCNTs@MSS was successfully synthesized by utilizing single-walled carbon nanotubes(SWCNTs)as cores and mesoporous silica shells(MSS)as coatings.The growth mechanism of MSS on SWCNTs was revealed based on the structural evolution process from helixes to mesostructures.The development of MSS on SWCNTs mainly included four stages:(i)the transition from surfactant helix to silica composite helix,(ii)the transition from inhomogeneous to homogeneous coating by gap filling process,(iii)the thickening of MSS,and(iv)the final framework condensation.The controllable synthesis of SWCNTs@MSS was realized by understanding the growth mechanism of MSS on SWCNTs.This composite nanofiber showed a lot of advantages including ordered mesostructures,tunable diameters,ease of surface modification,high drug-loading capacity,excellent dispersibility,and high ratio of length to diameter,which established a good foundation to construct a novel functional nanocoating.In chapter 5,a two-layered nanofibrous composite coating was successfully constructed on stents using EPD method.This novel composite coating utilized carboxylated SWCNTs(SWCNTs-COOH)to assemble the first thin inner layer,and amine functionalized SWCNTs@MSS(SWCNTs@MSS-NH₂)to construct the second functional layer.After the expansion process,no cracking and shedding of this coating was found because of the existence of SWCNTs-COOH buffer layer,the flexibility of SWCNTs@MSS-NH₂,the hydrogen bonding and carbon chain interactions between aminopropyl groups,and the electrostatic interactions between amino and carboxylic groups.This coating system also exhibited good hemocompatibility in vitro.The RAPA-loading amount on a stent was determined to be 119.23±6.63?g,which was 2.26-fold of the DES system in chapter 3.The drugs could be continuously released to 28 days,which was much longer than that reported in chapter 3.Finally,the animal experiment showed that this DES system with a network nanotopology had obvious advantages of early and rapid re-endotheliazation compared with the commercial P-FBII DES,which was beneficial to reduce the risks of LST.It was believed that this novel nanofibrous composite coating had promised future applications for the treatment of CAD.