The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial ...The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells(EC)and smooth muscle cells(SMC)in response to vascular injury,providing a promising therapeutic candidate to inhibit IRS.However,the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings.Here,we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)(PCL-PEG-PCL,PCEC)triblock copolymer spongy network.The miR-22 was used as a model microRNA to regulate SMC.The dynamic porous coating realized the uniform and controllable loading of miR-22,reaching the highest dosage of 133 pmol cm^(-2).We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC,thus leading to the EC dominating growth at an EC/SMC ratio of 5.4.More importantly,the PCEC@miR-22 coated stents showed reduced inflammation,low switching of SMC phenotype,and low secretion of extracellular matrix,which significantly inhibited IRS.This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent,which may extend to other combination medical devices,and facilitate practical application of bioactive agents in clinics.展开更多
基金This research was supported by the National Key Research and Development Program of China(2016YFC1102203)the National Natural Science Foundation of China(51933009,21875210)+3 种基金the Natural Key Research and Development Project of Zhejiang Province(2018C03015)Zhejiang Provincial Ten Thousand Talents Program(2018R52001)the Fundamental Research Funds for the Central Universities(2020FZZX003-01-03)the Higher Education Discipline Innovation Project(111 Project)under Grant No.B16042.
文摘The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells(EC)and smooth muscle cells(SMC)in response to vascular injury,providing a promising therapeutic candidate to inhibit IRS.However,the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings.Here,we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)(PCL-PEG-PCL,PCEC)triblock copolymer spongy network.The miR-22 was used as a model microRNA to regulate SMC.The dynamic porous coating realized the uniform and controllable loading of miR-22,reaching the highest dosage of 133 pmol cm^(-2).We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC,thus leading to the EC dominating growth at an EC/SMC ratio of 5.4.More importantly,the PCEC@miR-22 coated stents showed reduced inflammation,low switching of SMC phenotype,and low secretion of extracellular matrix,which significantly inhibited IRS.This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent,which may extend to other combination medical devices,and facilitate practical application of bioactive agents in clinics.
