Immobilization of heparin on biomaterials surface has been proven to be an effective strategy for preventing thrombus formation. However, the procedures of most immobilization methods（physical adsorption, covalent li...Immobilization of heparin on biomaterials surface has been proven to be an effective strategy for preventing thrombus formation. However, the procedures of most immobilization methods（physical adsorption, covalent linkage, electrostatic interaction） are complicated and time-consuming. In the present study, heparin with various concentrations immobilized on a titanium（Ti） substrate via polydopamine layer for improving blood compatibility was investigated. Water contact angle measurement showed that the immobilization of heparin resulted in an increase of the hydrophilicity. X-ray photoelectron spectroscopy（XPS） and Toluidine Blue O（TBO） tests displayed that the heparin molecules were successfully immobilized on Ti surface. The evaluations of blood compatibility（hemolysis rate, APTT, platelet adhesion and activation, fibrinogen conformational change） showed that the immobilization of heparin decreased hemolysis rate, prolonged blood coagulation time, reduced platelets adhesion and activation, and induced less fibrinogen conformational change. Moreover, a significant inhibition of blood coagulation and platelet adhesion was obtained when the heparin concentration was higher than 5 mg/mL, indicating that only with a certain surface densities could heparin perform its anticoagulant properties well. The results suggest that the immobilization of heparin via polydopamine layer can confer excellent antithrombotic properties, and the heparin immobilization method via polydopamine layer provides an alternative approach for other biomolecules immobilization on biomaterials surface. Thus it is envisaged that this method will be potentially useful for the surface modifi cation of blood-contacting biomaterials.展开更多
Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly（ethylene glycol） （APEG） was rapidly gra...Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly（ethylene glycol） （APEG） was rapidly grafted onto PU surface within 20 rain by a two-step method involving microwave-assisted MDI-functionalization and subsequent microwave-assisted APEG coupling. Then, heparin was eovalently immobilized through an amide linkage by the direct coupling of the carboxylic acid of heparin with the amino group of APEG on PU surface using carbodiimide coupling reaction. The surface structure and properties were characterized by X-ray photoelectron spectroscopy （XPS）, atomic force microscopy （AFM） and water contact angle measurements. The results revealed that hepadn-immobilized PU surface had slightly increased roughness and significantly improved hydrophilicity in comparison to the original PU surface. The anticoagulant activity of films was evaluated by whole blood clotting time （CT） and prothrombin time （PT）. Complement activation was assessed by detecting complement fragment 3a concentrations of serum exposed to the films. The results revealed that the microwave-assisted heparin-immobilized PU films had excellent antithrombogenicity and suppressed complement activation, indicating improved blood compatibility.展开更多
Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP f...Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP from one another. The blood compatibility of nHAP is also determined by blood solubil-ity experiment so that the capability of different dispersant dis-persing against nHAP of different concentration and the relation between nHAP and blood compatibility have been determined. The inhibiting function of Bel-7402 against tumor cells is deter-mined with the MTT staining method. The study result shows that heparin sodium has the best dispersing efficiency for nHAP with-out the phenomenon of hemolysis.展开更多
Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability.However,the in vivo rapid degradation rate and the insufficient biocompatib...Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability.However,the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications.In this study,the magnesium alloy(AZ31B)was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid,followed by the immobilization of chitosan-functionalized graphene oxide(GOCS).Heparin(Hep)and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer(LBL)to construct the GOCS/Hep bioactive multilayer coating,and the corrosion resistance and biocompatibility were extensively explored.The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance.The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation,resulting in an excellent blood compatibility.In addition,the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells,but also promote the vascular endothelial growth factor(VEGF)and nitric oxide(NO)expression of the attached endothelial cells on the surfaces.Therefore,the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys,which is expected to promote the application of magnesium alloys in biomaterials or medical devices,especially cardiovascular stent.展开更多
基金Funded by the Foundation of Jiangsu Provincial Key Laboratory for Interventional Medical Devices(JR1205)the National Natural Science Foundation of China(Nos.30870629,51175212)+2 种基金the Key Basic Research Program(2011CB606204)the Natural Science Research Program of Jiangsu Education Department(No.13KJB310014)the Natural Science Foundation of Nantong University(No.13R23)
文摘Immobilization of heparin on biomaterials surface has been proven to be an effective strategy for preventing thrombus formation. However, the procedures of most immobilization methods（physical adsorption, covalent linkage, electrostatic interaction） are complicated and time-consuming. In the present study, heparin with various concentrations immobilized on a titanium（Ti） substrate via polydopamine layer for improving blood compatibility was investigated. Water contact angle measurement showed that the immobilization of heparin resulted in an increase of the hydrophilicity. X-ray photoelectron spectroscopy（XPS） and Toluidine Blue O（TBO） tests displayed that the heparin molecules were successfully immobilized on Ti surface. The evaluations of blood compatibility（hemolysis rate, APTT, platelet adhesion and activation, fibrinogen conformational change） showed that the immobilization of heparin decreased hemolysis rate, prolonged blood coagulation time, reduced platelets adhesion and activation, and induced less fibrinogen conformational change. Moreover, a significant inhibition of blood coagulation and platelet adhesion was obtained when the heparin concentration was higher than 5 mg/mL, indicating that only with a certain surface densities could heparin perform its anticoagulant properties well. The results suggest that the immobilization of heparin via polydopamine layer can confer excellent antithrombotic properties, and the heparin immobilization method via polydopamine layer provides an alternative approach for other biomolecules immobilization on biomaterials surface. Thus it is envisaged that this method will be potentially useful for the surface modifi cation of blood-contacting biomaterials.
基金Funded by the National Natural Science Foundation of China(No.31170911)Research Development and Innovation Fund of Jinan University(No.21611410)Open Fund of The First Afliated Hospital,Jinan University
文摘Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly（ethylene glycol） （APEG） was rapidly grafted onto PU surface within 20 rain by a two-step method involving microwave-assisted MDI-functionalization and subsequent microwave-assisted APEG coupling. Then, heparin was eovalently immobilized through an amide linkage by the direct coupling of the carboxylic acid of heparin with the amino group of APEG on PU surface using carbodiimide coupling reaction. The surface structure and properties were characterized by X-ray photoelectron spectroscopy （XPS）, atomic force microscopy （AFM） and water contact angle measurements. The results revealed that hepadn-immobilized PU surface had slightly increased roughness and significantly improved hydrophilicity in comparison to the original PU surface. The anticoagulant activity of films was evaluated by whole blood clotting time （CT） and prothrombin time （PT）. Complement activation was assessed by detecting complement fragment 3a concentrations of serum exposed to the films. The results revealed that the microwave-assisted heparin-immobilized PU films had excellent antithrombogenicity and suppressed complement activation, indicating improved blood compatibility.
基金Supported by the National Basic Research Program of China(973 Program) (2005CB623905)
文摘Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP from one another. The blood compatibility of nHAP is also determined by blood solubil-ity experiment so that the capability of different dispersant dis-persing against nHAP of different concentration and the relation between nHAP and blood compatibility have been determined. The inhibiting function of Bel-7402 against tumor cells is deter-mined with the MTT staining method. The study result shows that heparin sodium has the best dispersing efficiency for nHAP with-out the phenomenon of hemolysis.
基金financially supported by the National Natural Science Foundation of China(31870952)Natural Science Foundation of Jiangsu Province of China(BK20181480)+2 种基金The Key Program of National Natural Science Foundation of China(31830028)the International S&T Cooperation Program of Huai'an City of China(HAC201703)the Key Program for Natural Science Foundation of Jiangsu Higher Education Institutions of China(17KJA530002).
文摘Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability.However,the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications.In this study,the magnesium alloy(AZ31B)was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid,followed by the immobilization of chitosan-functionalized graphene oxide(GOCS).Heparin(Hep)and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer(LBL)to construct the GOCS/Hep bioactive multilayer coating,and the corrosion resistance and biocompatibility were extensively explored.The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance.The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation,resulting in an excellent blood compatibility.In addition,the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells,but also promote the vascular endothelial growth factor(VEGF)and nitric oxide(NO)expression of the attached endothelial cells on the surfaces.Therefore,the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys,which is expected to promote the application of magnesium alloys in biomaterials or medical devices,especially cardiovascular stent.
