In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellula...In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.展开更多
Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been r...Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.展开更多
Thrombosis and infection are two major complications associated with central venous catheters(CVCs),which significantly contribute to morbidity and mortality.Antifouling coating strategies currently represent an effic...Thrombosis and infection are two major complications associated with central venous catheters(CVCs),which significantly contribute to morbidity and mortality.Antifouling coating strategies currently represent an efficient approach for addressing such complications.However,existing antifouling coatings have limitations in terms of both duration and effectiveness.Herein,we propose a durable zwitterionic polymer armor for catheters.This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization,followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine(pMPC)via in-situ radical polymerization.The resulting pMPC coating armor exhibits super-hydrophilicity,thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro.In practical applications,the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model,as well as inhibited thrombus formation in a rabbit jugular vein model.Overall,our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.展开更多
Proteins,cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection,resulting in significant clinical mortality.Here,we report a zwitterionic polymers-armored amyloid-like prote...Proteins,cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection,resulting in significant clinical mortality.Here,we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as“armored-tank”strategy for dual functionalization of medical devices.The“armored-tank”strategy is realized by decoration of partially conformational transformed LZM(PCTL)assembly through oxidant-mediated process,followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine(pMPC).The outer armor of the“armored-tank”shows potent and durable zone defense against fibrinogen,platelet and bacteria adhesion,leading to long-term antithrombogenic properties over 14 days in vivo without anticoagulation.Additionally,the“fired”PCTL from“armored-tank”actively and effectively kills both Gram-positive and Gram-negative bacterial over 30 days as a supplement to the lacking bactericidal functions of passive outer armor.Overall,this“armored-tank”surface engineering strategy serves as a promising solution for preventing biofouling and thrombotic occlusion of medical devices.展开更多
In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphos...In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate （ADP）, thrombin, arachidonic acid （AA） and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an ICs0 value of 899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B （2-10 mg/kg, ig） significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8-14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.展开更多
As a coagulation factor in the intrinsic coagulation pathway,factor XIa(FXIa)is an effective and safe target for the development of antithrombotic drugs.Many small-molecule FXIa inhibitors have been discovered,some of...As a coagulation factor in the intrinsic coagulation pathway,factor XIa(FXIa)is an effective and safe target for the development of antithrombotic drugs.Many small-molecule FXIa inhibitors have been discovered,some of which are being evaluated in clinical trials.However,none of them have been approved.In the present study,a highly selective potent FXIa inhibitor with poor solubility reported in our previous work was selected as a lead compound to be further modified to improve FXIa potency and physicochemical properties.The structure-based drug design and structure-activity relationship study led to the discovery of LY8,LY17,and LY25,which demonstrated enhanced FXIa potency and maintained excellent selectivity.In addition,LY8 exhibited significantly improved aqueous solubility,suggesting that it could be a promising compound to be further evaluated.展开更多
基金supported by grants from the National Key Research and Development Program of China (2016YFC1101400, 2016YFC1102903)the National Natural Science Foundation of China (31670995, 81470679)
文摘In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.
基金supported by National Key Research and Development Programs,China(2022YFB3807305 and 2022YFB3807303)National Natural Science Foundation of China(32071357).
文摘Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.
基金supported by the National Natural Science Foundation of China (Project 82072072,32261160372,32171326,32371377)the Guangdong Basic and Applied Basic Research Foundation (2022B1515130010,2021A1515111035)Dongguan Science and Technology of Social Development Program (20231800906311,20231800900332).
文摘Thrombosis and infection are two major complications associated with central venous catheters(CVCs),which significantly contribute to morbidity and mortality.Antifouling coating strategies currently represent an efficient approach for addressing such complications.However,existing antifouling coatings have limitations in terms of both duration and effectiveness.Herein,we propose a durable zwitterionic polymer armor for catheters.This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization,followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine(pMPC)via in-situ radical polymerization.The resulting pMPC coating armor exhibits super-hydrophilicity,thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro.In practical applications,the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model,as well as inhibited thrombus formation in a rabbit jugular vein model.Overall,our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.
基金supported by by the National Natural Science Foundation of China(Project 82202325,82072072,32171326,32261160372)the Guang Dong Basic and Applied Basic Research Foundation(2022B1515130010,2021A1515111035)China Postdoctoral Science Foundation(2022M721524).
文摘Proteins,cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection,resulting in significant clinical mortality.Here,we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as“armored-tank”strategy for dual functionalization of medical devices.The“armored-tank”strategy is realized by decoration of partially conformational transformed LZM(PCTL)assembly through oxidant-mediated process,followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine(pMPC).The outer armor of the“armored-tank”shows potent and durable zone defense against fibrinogen,platelet and bacteria adhesion,leading to long-term antithrombogenic properties over 14 days in vivo without anticoagulation.Additionally,the“fired”PCTL from“armored-tank”actively and effectively kills both Gram-positive and Gram-negative bacterial over 30 days as a supplement to the lacking bactericidal functions of passive outer armor.Overall,this“armored-tank”surface engineering strategy serves as a promising solution for preventing biofouling and thrombotic occlusion of medical devices.
基金Natural Science Foundation of China (Grant No.813 02763)Beijing Natural Science Foundation (Grant No.7144218)
文摘In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate （ADP）, thrombin, arachidonic acid （AA） and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an ICs0 value of 899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B （2-10 mg/kg, ig） significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8-14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.
基金National Natural Science Foundation of China(Grant No.81803352)。
文摘As a coagulation factor in the intrinsic coagulation pathway,factor XIa(FXIa)is an effective and safe target for the development of antithrombotic drugs.Many small-molecule FXIa inhibitors have been discovered,some of which are being evaluated in clinical trials.However,none of them have been approved.In the present study,a highly selective potent FXIa inhibitor with poor solubility reported in our previous work was selected as a lead compound to be further modified to improve FXIa potency and physicochemical properties.The structure-based drug design and structure-activity relationship study led to the discovery of LY8,LY17,and LY25,which demonstrated enhanced FXIa potency and maintained excellent selectivity.In addition,LY8 exhibited significantly improved aqueous solubility,suggesting that it could be a promising compound to be further evaluated.
