miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis

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, providi...

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Main Authors: Jing Wang, Hong-Lin Qian, Sheng-Yu Chen, Wei-Pin Huang, Dan-Ni Huang, Hong-Ye Hao, Ke-Feng Ren, Yun-Bing Wang, Guo-Sheng Fu, Jian Ji
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2021-12-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21002139
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author Jing Wang
Hong-Lin Qian
Sheng-Yu Chen
Wei-Pin Huang
Dan-Ni Huang
Hong-Ye Hao
Ke-Feng Ren
Yun-Bing Wang
Guo-Sheng Fu
Jian Ji
author_facet Jing Wang
Hong-Lin Qian
Sheng-Yu Chen
Wei-Pin Huang
Dan-Ni Huang
Hong-Ye Hao
Ke-Feng Ren
Yun-Bing Wang
Guo-Sheng Fu
Jian Ji
author_sort Jing Wang
collection DOAJ
description 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.
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spelling doaj.art-609bfb92b34b4677bad82be162f87b3f2024-04-17T03:24:51ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-12-0161246864696miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosisJing Wang0Hong-Lin Qian1Sheng-Yu Chen2Wei-Pin Huang3Dan-Ni Huang4Hong-Ye Hao5Ke-Feng Ren6Yun-Bing Wang7Guo-Sheng Fu8Jian Ji9MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China; Corresponding author. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China; Corresponding author.Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China; Corresponding author.MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, ChinaThe 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.http://www.sciencedirect.com/science/article/pii/S2452199X21002139microRNASpongy coatingBiodegradable stentContractile phenotypeRestenosis
spellingShingle Jing Wang
Hong-Lin Qian
Sheng-Yu Chen
Wei-Pin Huang
Dan-Ni Huang
Hong-Ye Hao
Ke-Feng Ren
Yun-Bing Wang
Guo-Sheng Fu
Jian Ji
miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
Bioactive Materials
microRNA
Spongy coating
Biodegradable stent
Contractile phenotype
Restenosis
title miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
title_full miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
title_fullStr miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
title_full_unstemmed miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
title_short miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis
title_sort mir 22 eluting cardiovascular stent based on a self healable spongy coating inhibits in stent restenosis
topic microRNA
Spongy coating
Biodegradable stent
Contractile phenotype
Restenosis
url http://www.sciencedirect.com/science/article/pii/S2452199X21002139
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