Construction Of Multifunctional Coatings For Cardiovascular Devices Via Layer-By-Layer Self-Assembly Of Hyperbranched Polyethers

Much attention has been paid to the application of layer-by-layer(LBL) films as functional surface coatings of implanted medical devices(such as vascular catheters, vascular implants,and heart valves).They appear as interesting candidates for the localized delivery of therapeutic agents,antibacterial and anticoagulation applications, control of cell adhesion and growth,and so on.Toward the goal of constructing multifunctional LBL films,hyperbranched polyether is used as a building block for LBL assembly,and multilayer films via electrostatic or covalent LBL assembly technique have been constructed,respectively.Construction of multifunctional coatings via the electrostatic LBL assembly of heparin-like hyperbrabched polyetherA water soluble sulfonated hyperbranched polyether(HBPO-SO₃),consisting of a hydrophobic hyperbranched poly(3-ethyl-3-oxetanemethanol) core and sulfonate terminal groups,is designed as a promising heparin-like biomaterial.The micellization of the resultant HBPO-SO₃ in aqueous solution is monitored by fluorescence spectroscopy using pyrene as a hydrophobic probe and the critical micelle concentration(CMC) is determined to be 0.017 mg/mL.The analyses of transmission electron microscopy(TEM) clearly show that HBPO-SO₃ can aggregate into spherical micelles with diameters of 25～70 nm above CMC.Results from the plasma recalcification time assay and cell culture declare that HBPO-SO₃ exhibits good hemocompatibility and low cytotoxicity.As an alternative to heparin,sulfonated hyperbranched polyether HBPO-SO₃ is employed as a building block to fabricate multilayer films with chitosan via LBL assembly.The atomic force microscopy(AFM) images demonstrate the stability of HBPO-SO₃ micelles during the LBL process and therefore many hydrophobic nanodomains are incorporated into the LBL films to provide nanoreservoirs for hydrophobic guest molecules.The fluorescence emission spectra verify that the hydrophobic dye pyrene can be incorporated into the LBL films either by pre-encapsulation in HBPO-SO₃ micelles or post-diffusion in preassembled multilayer films.Compared with the pre-encapsulation approach,the post-diffusion process is more efficient to incorporate hydrophobic guest molecules into the LBL films and can carry out a much more controlled release of the guest molecules.Hydrophobic drug probucal,which has powerful antioxidant properties and can prevent restenosis after coronary angioplasty,is chosen and incorporated into multilayer films via post-diffusion.Successful loading and controlled release of probucal in HBPO-SO₃/chitosan multilayer films are obtained.In addition,HBPO-SO₃/chitosan multilayer films exhibit anticoagulant activity even with chitosan as the outmost layer. Therefore,a multifunctional coating with potential anticoagulation,antibacterial and localized release of hydrophobic drug is developed.Construction of multifunctional coating via the covalent LBL assembly of reactive hyperbranched polyetherThe construction of multilayer films via the alternating covalent LBL assembly of p-nitrophenyloxycarbonyl groups-terminated hyperbranched polyether (HBPO-NO₂) and polyethylenimine(PEI) onto aminolyzed substrates is investigated. Ellipsometry measurements confirm the successful LbL assembly of HBPO-NO₂ and PEI.Results from contact angle measurements and UV-vis spectrum demonstrate that 5-bilayered multilayer films form uniform surface coatings on the substrate surface. HBPO-NO₂/PEI multilayer films can be used as localized delivery carriers for multiple therapeutic agents because of the distinct properties of the building blocks. The loading behaviors of HBPO-NO₂/PEI multilayer films toward hydrophilic anionic dye ponceau 2R can be controlled by the protonation of PEI,and ponceau 2R-loaded multilayer films prepared at neutral pH value exhibit well loading and release behaviors.By making use of the effective chelating capability of PEI to Ag⁺,Ag⁺ is loaded into the LBL films and then is in situ photoreduced into Ag nanoparticles in the multilayers template.The amount of Ag nanoparticles increases with the increasing of the number of PEI layers in the LBL films.The hydrophobic hyperbranched polyether chains can be regarded as reservoirs for hydrophobic guest molecules,and the LBL films are capable of controlled loading and release of hydrophobic drug probucal.Results from cell experiments indicate that increasing the thickness of the LBL films,human umbilical vein endothelial cells(HUVECs) adhesion and proliferation on the LBL surface are obviously decreased.The multilayer films with HBPO-NO₂ as the outmost layer react readily with the nucleophilic N-terminus of the extracellular matrix proteins collagen or peptide REDV to achieve biomimetic surfaces.The adhesion and growth of HUVECs for the biomolecules-grafted surfaces are better than that of ungrafted multilayer films. Especially,the immobilization of collagen on the surface of 5.5-bilayered multilayer films significantly improves the HUVECs adhesion and proliferation.Therefore,the LBL films exhibit excellent capabilities of localized delivery of multiple therapeutic agents and control of cell function.The facile method here to prepare multifunctional LBL films may have good potential for surface modification of cardiovascular devices.