It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabili...It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabilities of different coatings on stents(e.g.gelatin,anti-CD133 and anti-CD34 antibodies)to promote adhesion and proliferation of endothelial progenitor cells(EPCs).The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress,so that allowing for the growth of the cells on the slides for 48 h.The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents(BMS)and gelatin-coated stents.Compared with the anti-CD34 antibody-coated stents,the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR.In conclusion,this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR.展开更多
Treatments of atherogenesis,one of the most common cardiovascular diseases(CVD),are continuously being made thanks to innovation and an increasingly in-depth knowledge of percutaneous transluminal coronary angioplasty...Treatments of atherogenesis,one of the most common cardiovascular diseases(CVD),are continuously being made thanks to innovation and an increasingly in-depth knowledge of percutaneous transluminal coronary angioplasty(PTCA),the most revolutionary medical procedure used for vascular restoration.Combined with an expanding balloon,vascular stents used at stricture sites enable the long-time restoration of vascular permeability.However,complication after stenting,in-stent restenosis(ISR),hinders the advancement of vascular stents and are associated with high medical costs for patients for decades years.Thus,the development of a high biocompatibility stent with improved safety and efficiency is urgently needed.This review provides an overview of current advances and potential technologies for the modification of stents for better treatment and prevention of ISR.In particular,the mechanisms of in-stent restenosis are investigated and summarized with the aim to comprehensively understanding the pathogenesis of stent complications.Then,according to different therapeutic functions,the current stent modification strategies are reviewed,including polymeric drug eluting stents,biological friendly stents,prohealing stents,and gene stents.Finally,the review provides an outlook of the challenges in the design of stents with optimal properties.Therefore,this review is a valuable and practical guideline for the development of cardiovascular stents.展开更多
Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation.Targeting the interplay between inflammation and coagulation,and smooth muscle cell(...Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation.Targeting the interplay between inflammation and coagulation,and smooth muscle cell(SMC)proliferation,we presented a microenvironment-responsive coating designed to regulate tissue responses and vascular regeneration throughout the remodeling process.Coagulation was inhibited by incorporating anticoagulant tirofiban into the coating.MMP9-responsive nanoparticles embedded in the coating released salvianolic acid A to modulate inflammatory cell behavior and inhibit SMC dysfunction.By effectively interfering with clotting and inflammation,the coating suppressed platelet-fibrin interaction and formation of plateletmonocyte aggregates,thereby mitigating adverse effects on reendothelialization.Its ability to influence SMC proliferation and migration resulted in reduced intimal hyperplasia.Coated stents were shown to significantly regulate tissue regeneration,improve the vascular environment and even reduced the lipid content in the nar-rowed atherosclerotic vessels in vivo.This direct approach enhanced the vascular tissue regeneration after stent implantation,and offered promising insights for optimizing vascular stent design.展开更多
Rare-earth-free magnesium(Mg)alloy bioresorbable stent(BRS)exhibits significant potential in vascular intervention due to its exceptional biosafety.However,its susceptibility to corrosion complicates surface func-tion...Rare-earth-free magnesium(Mg)alloy bioresorbable stent(BRS)exhibits significant potential in vascular intervention due to its exceptional biosafety.However,its susceptibility to corrosion complicates surface func-tionalization and renders existing coating strategies ineffective for degradation-remodeling kinetics,resulting in delayed re-endothelialization and excessive lumen loss.Herein,a hierarchical MgF_(2)/polyurethane(PU)/pit-avastatin(PTV)coating system is constructed on Mg-Zn-Mn BRS using elastomeric PU as an intermediate layer.Studies confirm the PU layer effectively accommodates stent deformation,alleviates stress concentrations,and confines corrosion propagation triggered by deformation-induced MgF_(2) microcracks.The in situ formed MgF_(2) layer concurrently decreases substrate reactivity,establishes stable interfaces with PU,and synergistically en-hances the corrosion resistance.The surface PTV-loaded poly-L-lactic acid layer maintains sustained drug release through PU-mediated interfacial stability while serving as an initial corrosion barrier.In vivo evaluations demonstrate the MgF_(2)/PU/PTV-functionalized stent significantly suppresses neointimal hyperplasia in rabbit models while achieving synchronized degradation-remodeling kinetics.This hierarchical coating architecture,which synergistically integrates controlled drug elution with degradation modulation,provides a viable solution to clinical challenges of post-implant restenosis and vascular remodeling mismatch.展开更多
An increased level of reactive oxygen species(ROS)plays a major role in endothelial dysfunction and vascular smooth muscle cell(VSMC)proliferation during in-stent thrombosis and restenosis after coronary artery stenti...An increased level of reactive oxygen species(ROS)plays a major role in endothelial dysfunction and vascular smooth muscle cell(VSMC)proliferation during in-stent thrombosis and restenosis after coronary artery stenting.Herein,we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPOL)and rapamycin(RAPA)that correspondingly serves as an ROS scavenger and VSMC inhibitor.This system has the potential to improve the biocompatibility of current drug-eluting stent(DES)coatings with the long-term and continuous release of TEMPOL and rapamycin.Moreover,the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells(ECs).This membrane demonstrated superior ROS-scavenging,anti-inflammatory and antithrombogenic effects in ECs.In addition,the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB(PDGF-BB)-induced proliferation of VSMCs.In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.展开更多
基金This study was partially supported by grants-in-aid from the National Natural Science Foundation of China(11332003,31370949)the National Key Technology R&D Program of China(2012BAI18B02)the National Key Basic Research Program of China(2012CB619101)。
文摘It is not clear what effects of CD34-and CD133-specific antibody-coated stents have on reendothelialization and in-stent restenosis(ISR)at the early phase of vascular injury.This study aims at determining the capabilities of different coatings on stents(e.g.gelatin,anti-CD133 and anti-CD34 antibodies)to promote adhesion and proliferation of endothelial progenitor cells(EPCs).The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress,so that allowing for the growth of the cells on the slides for 48 h.The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents(BMS)and gelatin-coated stents.Compared with the anti-CD34 antibody-coated stents,the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR.In conclusion,this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR.
基金financial support from the National Key Research and Development Program of China(2017YFB0702500)Natural Science Foundation of China(NSFC Project,81801853)Sichuan Science and Technology Program(19GJHZ0058)。
文摘Treatments of atherogenesis,one of the most common cardiovascular diseases(CVD),are continuously being made thanks to innovation and an increasingly in-depth knowledge of percutaneous transluminal coronary angioplasty(PTCA),the most revolutionary medical procedure used for vascular restoration.Combined with an expanding balloon,vascular stents used at stricture sites enable the long-time restoration of vascular permeability.However,complication after stenting,in-stent restenosis(ISR),hinders the advancement of vascular stents and are associated with high medical costs for patients for decades years.Thus,the development of a high biocompatibility stent with improved safety and efficiency is urgently needed.This review provides an overview of current advances and potential technologies for the modification of stents for better treatment and prevention of ISR.In particular,the mechanisms of in-stent restenosis are investigated and summarized with the aim to comprehensively understanding the pathogenesis of stent complications.Then,according to different therapeutic functions,the current stent modification strategies are reviewed,including polymeric drug eluting stents,biological friendly stents,prohealing stents,and gene stents.Finally,the review provides an outlook of the challenges in the design of stents with optimal properties.Therefore,this review is a valuable and practical guideline for the development of cardiovascular stents.
基金supported by grants from the National Natural Science Foundation of China(No.32301100,82270262)the Natural Science Foundation of Zhejiang Province,China(Grant No.LQ24C100003,LY23H020005).
文摘Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation.Targeting the interplay between inflammation and coagulation,and smooth muscle cell(SMC)proliferation,we presented a microenvironment-responsive coating designed to regulate tissue responses and vascular regeneration throughout the remodeling process.Coagulation was inhibited by incorporating anticoagulant tirofiban into the coating.MMP9-responsive nanoparticles embedded in the coating released salvianolic acid A to modulate inflammatory cell behavior and inhibit SMC dysfunction.By effectively interfering with clotting and inflammation,the coating suppressed platelet-fibrin interaction and formation of plateletmonocyte aggregates,thereby mitigating adverse effects on reendothelialization.Its ability to influence SMC proliferation and migration resulted in reduced intimal hyperplasia.Coated stents were shown to significantly regulate tissue regeneration,improve the vascular environment and even reduced the lipid content in the nar-rowed atherosclerotic vessels in vivo.This direct approach enhanced the vascular tissue regeneration after stent implantation,and offered promising insights for optimizing vascular stent design.
基金supported by Natural Science Foundation of China(Project 32171326,32371377,32471376,32261160372)the Post-doctoral Fellowship Program(Grade C)of China Postdoctoral Science Foundation(Grant Number GZC20240667)+3 种基金The Third People’s Hospital of Chengdu Scientific Research Project(2023PI06)the Guang Dong Basic and Applied Basic Research Foundation(2022B1515130010)Dongguan Science and Technology of Social Development Program(20231800906311)the Leading Talent Project of Guangzhou Development District(2020-L013).
文摘Rare-earth-free magnesium(Mg)alloy bioresorbable stent(BRS)exhibits significant potential in vascular intervention due to its exceptional biosafety.However,its susceptibility to corrosion complicates surface func-tionalization and renders existing coating strategies ineffective for degradation-remodeling kinetics,resulting in delayed re-endothelialization and excessive lumen loss.Herein,a hierarchical MgF_(2)/polyurethane(PU)/pit-avastatin(PTV)coating system is constructed on Mg-Zn-Mn BRS using elastomeric PU as an intermediate layer.Studies confirm the PU layer effectively accommodates stent deformation,alleviates stress concentrations,and confines corrosion propagation triggered by deformation-induced MgF_(2) microcracks.The in situ formed MgF_(2) layer concurrently decreases substrate reactivity,establishes stable interfaces with PU,and synergistically en-hances the corrosion resistance.The surface PTV-loaded poly-L-lactic acid layer maintains sustained drug release through PU-mediated interfacial stability while serving as an initial corrosion barrier.In vivo evaluations demonstrate the MgF_(2)/PU/PTV-functionalized stent significantly suppresses neointimal hyperplasia in rabbit models while achieving synchronized degradation-remodeling kinetics.This hierarchical coating architecture,which synergistically integrates controlled drug elution with degradation modulation,provides a viable solution to clinical challenges of post-implant restenosis and vascular remodeling mismatch.
基金supported by the National Natural Science Foundation of China(No.82170342)the Shanghai Engineering Research Center of Interventional Medicine(No.19DZ2250300)+2 种基金the National Key R&D Program of China(No.2021YFA1201300 and No.2020YFC1316703)the Chinese Academy of Medical Sciences(2019-I2M-5-060,2020-JKCS-0154020)the Shanghai Shenkang Hospital Development Center(SHDC2020CR3023B).
文摘An increased level of reactive oxygen species(ROS)plays a major role in endothelial dysfunction and vascular smooth muscle cell(VSMC)proliferation during in-stent thrombosis and restenosis after coronary artery stenting.Herein,we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPOL)and rapamycin(RAPA)that correspondingly serves as an ROS scavenger and VSMC inhibitor.This system has the potential to improve the biocompatibility of current drug-eluting stent(DES)coatings with the long-term and continuous release of TEMPOL and rapamycin.Moreover,the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells(ECs).This membrane demonstrated superior ROS-scavenging,anti-inflammatory and antithrombogenic effects in ECs.In addition,the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB(PDGF-BB)-induced proliferation of VSMCs.In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.
