Advanced Healthcare Materials
·
2022
·Vol. 11
·期 17
·2200965
·
IF 11.092
Yi Cheng,Xiaoxuan Zhang,Rui Liu,Yazhou Li,Jiaqi Zeng,Min Zhou,Yuanjin Zhao
In-stent restenosis (ISR) is seriously affecting the long-term prognosis of vascular interventional therapy and leading to enormous medical burdens. Great efforts have been devoted to developing functional vascular stents with desired features and properties for effective ISR prevention. Here, a multifunctional bionic vascular stent with designed coatings prepared using microfluidic electrospinning technology is presented. Such stents are composed of biocompatible, drug-loaded methylacrylated gelatin-polyethylene glycol diacrylate (GelMA-PEGDA) and polycaprolactone composite nanofibers on 316L stainless steel stents by an easy-to-operate step-by-step spraying method. Benefitting from the addition of polydopamine during the fabrications, the drug-loaded composite nanofibers can adhere well to both the stent and the vascular wall. Furthermore, as the inner fibrous layer of the stent contacting the lumen is equipped with heparin-vascular endothelial growth factor (Hep-VEGF), it plays an anticoagulation role and promotes the growth of endothelial cells; while the outer layer contacts the vascular wall and releases rapamycin slowly, which can restrain smooth muscle proliferation. By implanting this into the rabbit carotid artery, the multi-functional bionic demonstrates that the vascular stent can achieve good anti-thrombosis and in-stent restenosis effects, which indicates its potential values in vascular intervention and other biomedical fields.
研究领域:
生物医学工程
·
心血管病学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 21
·2002330
·
IF 15.84
Nan Lyu,Zeyu Du,Hua Qiu,Peng Gao,Qin Yao,Kaiqin Xiong,Qiufen Tu,Xiangyang Li,Binghai Chen,Miao Wang,Guoqing Pan,Nan Huang,Zhilu Yang
Endothelium can secrete vasoactive mediators and produce specific extracellular matrix, which contribute jointly to the thromboresistance and regulation of vascular cell behaviors. From a bionic point of view, introducing endothelium-like functions onto cardiovascular stents represents the most effective means to improve hemocompatibility and reduce late stent restenosis. However, current surface strategies for vascular stents still have limitations, like the lack of multifunctionality, especially the monotony in endothelial-mimic functions. Herein, a layer-by-layer grafting strategy to create endothelium-like dual-functional surface on cardiovascular scaffolds is reported. Typically, a nitric oxide (NO, vasoactive mediator)-generating compound and an endothelial polysaccharide matrix molecule hyaluronan (HA) are sequentially immobilized on allylamine-plasma-deposited stents through aqueous amidation. In this case, the stents could be well-engineered with dual endothelial functions capable of remote and close-range regulation of the vascular microenvironment. The synergy of NO and endothelial glycocalyx molecules leads to efficient antithrombosis, smooth muscle cell (SMC) inhibition, and perfect endothelial cell (EC)-compatibility of the stents in vitro. Moreover, the dual-functional stents show efficient antithrombogenesis ex vivo, rapid endothelialization, and long-term prevention of restenosis in vivo. Therefore, this study will provide new solutions for not only multicomponent surface functionalization but also the bioengineering of endothelium-mimic vascular scaffolds with improved clinical outcomes.
研究领域:
生物医学工程
·
心血管科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jiayi Zhang,Yang Li,Zhen Xiang,Daihua Fu,Yunbing Wang
Cardiovascular stents persistently struggle to reconcile rapid endothelialization with long-term prevention of thrombosis and restenosis. This study develops a spatiotemporally orchestrated dual-gas-releasing hydrogel coating that synchronizes H 2 S and NO delivery with the dynamic phases of vascular healing. The coating is fabricated by covalently grafting an alginate coating onto poly(L-lactic acid) stents via a benzophenone-mediated two-step surface photopolymerization. A thiol‑activated H 2 S donor is anchored within the coating, while alginate‑chelated Cu 2 ⁺ catalyzes NO generation from endogenous S‑nitrosothiols. An early H 2 S burst synergizes with NO to suppress thromboinflammation and prime a regenerative niche, while sustained NO release maintains vascular homeostasis and directs long-term remodeling. The coating reduces platelet adhesion by over 90%, virtually eliminates thrombosis in an arteriovenous shunt model, triples endothelial coverage, and suppresses smooth muscle cell proliferation by ≈73%. It also reprograms macrophage polarization, increasing the M2/M1 ratio tenfold, and reduces intracellular ROS levels by >90%. In a rabbit abdominal aorta model, the coating promotes flow-aligned endothelialization, achieving CD31⁺/eNOS⁺ coverage comparable to native tissue within 3 months, while decreasing neointimal thickness by 66% versus controls. This spatiotemporally tailored gasotransmitter delivery resolves the healing dichotomy of stents, providing a clinically translatable platform for next-generation vascular implants.
研究领域:
生物材料学
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心血管医学
·
再生医学
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纳米医学
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转化医学
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分子药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yi-jing Yin,Xing-wang Wang,Wei-qi Lu,Zhao-yang Chen,Jia-yin Fu,Ke-feng Ren,Jian Ji
Restenosis, the re-narrowing of blood vessels after drug-coated balloons (DCBs), remains a major clinical issue. While rapamycin is the current clinical option for preventing restenosis due to its effectiveness and low toxicity, its delivery is limited by poor tissue absorption and rapid clearance, leading to suboptimal drug retention. Here, we developed the adhesive-polyelectrolyte- co ated poly(lactic- co -glycolic acid) (PLGA) particles using in-situ UV-triggered polymerization, encapsulating rapamycin. This system combines PLGA's sustained release with a robust adhesive coating that enhances vascular wall binding, by hydrogen bonding and covalent bonding. Rapamycin retention improved by 835 % in vitro (1 week) and 525 % in vivo (4 weeks) compared to uncoated particles. This approach offers a promising strategy to enhance rapamycin delivery, improving the safety and efficacy of DCBs in treating vessel obstruction.
研究领域:
生物医学工程
·
药剂学
·
心血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 3
·535
·
IF 6.525
Huiru Zhu,Li Kong,Xu Zhu,Tingting Ran,Xiaojuan Ji
A high incidence of restenosis has been reported at the site of inflammation following angioplasty and stent implantation. The anti-proliferative drug paclitaxel (PTX) could help to reduce inflammation and restenosis; however, it has poor water solubility and serious adverse side effects at high doses. Given the presence of metabolic acidosis at the site of inflammation, we hypothesized that nanoparticles that are responsive to low pH could precisely release the loaded drug at the target site. We successfully constructed pH-responsive poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTX and NaHCO3as a pH-sensitive therapeutic agent (PTX-NaHCO3-PLGA NPs). The NPs exhibited remarkable pH sensitivity and a good safety profile both in vitro in rat vascular smooth muscle cells and in vivo in Sprague Dawley rats after tail vein injection. In the rat model, the PTX-NaHCO3-PLGA NPs treatment group showed suppressed intimal proliferation following balloon-induced carotid artery injury compared with that of the saline-treated control. Overall, these results demonstrate that our newly developed pH-responsive nanodrug delivery platform has the potential to effectively inhibit restenosis.Keywords:vascular restenosis;pH-responsive nanoparticles;sodium bicarbonate;paclitaxel;drug delivery
研究领域:
医学
·
药学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Tianshu Chu,Chun Dai,Xiang Li,Lei Gao,Hongyan Yin,Jianjun Ge
Following vein grafting, the vein must adapt to arterial hemodynamics, which can lead to intimal hyperplasia (IH) and restenosis. Moreover, endothelial-to-mesenchymal transition (EndMT) components are highly associated with IH. Therefore, in this study, we aimed to design an extravascular film loaded with rapamycin (extravascular rapamycin film [ERF]) to limit vein graft stenosis. The film exhibited stable physicochemical properties as well as in vivo and in vitro biocompatibility. In vivo , the film inhibited the EndMT by activating the autophagy pathway. Moreover, rapamycin enhanced this biological effect. Collectively, these findings highlighted the applicability of ERF as a new therapeutic target for preventing vein graft restenosis.
研究领域:
心血管医学
·
药理学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
Nanoscale
·
2015
·Vol. 7
·期 17
·7682-7691
·
IF 7.394
Zhiyou Peng,Jinbao Qin,Bo Li,Kaichuang Ye,Yuxin Zhang,Xinrui Yang,Fukang Yuan,Lijia Huang,Junqing Hu,Xinwu Lu
Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE−/− mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.
研究领域:
生物医学工程
·
心血管疾病
·
纳米技术
·
治疗方法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
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
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.
研究领域:
心脏病学
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药剂学
·
生物材料
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Brazilian Journal of Cardiovascular Surgery
·
2015
·Vol. 30
·期 2
·159-163
·
IF 0.55
Song Chun-Li,Li Qian,Yu Yun-Peng,Wang Guan,Wang Jin-Peng,Lu Yang,Zhang Ji-Chang,Diao Hong-Ying,Liu Jian-Gen,Liu Yi-Hang,Liu Jia,Li Ying,Cai Dan,Liu Bin
Introduction: Intravascular coronary stenting has been used in the treatment of coronary artery disease (CAD), with a major limitation of in-stent restenosis (ISR). The 316 stainless steel has been widely used for coronary stents. In this study, we developed a novel coating method to reduce ISR by simultaneously coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on 316L stainless steel. Methods: Round 316L stainless steel sheets in the D-H group were polymerized with compounds generated from condensation reaction of dopamine and heparin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after another for 10 times, and named as the D-(H-V)10 group. Eight sheets from the D-(H-V)10 group were coated with anti-CD34 antibody and termed as the D-(H-V)10-A group. Immunofluorescence assay and ELISA were used to evaluate whether the 316L stainless steel disks were successfully coated with VEGF and anti-CD34 antibody. Results: The results of immunofluorescence assay and ELISA showed that VEGF could be detected in the D-(H-V)10 and D-(H-V)10-A group, suggesting the steel sheets were successfully covered with VEGF. Anti-CD34 antibody could only be observed in the D-(H-V)10-A group, which was the only group coated with CD34 antibody. Both results suggested that the 316L stainless steel sheets were successfully coated with VEGF and anti-CD34 antibody. Conclusion: Our study developed a method to simultaneously coat VEGF and anti-CD34 antibody to stainless metal steel. This research serves as a fundamental role for a novel coating strategy.
研究领域:
心血管工程
·
生物材料
·
医疗器械
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2020
·
IF 3.557
Tianyu Zhu,Min Zhou,Wentao Gao,Dan Fang,Zhiyong Liu,Guangyan Wu,Mimi Wan,Chun Mao,Jian Shen
In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay, in vitro coagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.
研究领域:
心脏病学
·
纳米技术
·
生物材料
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Zhining Zhuo,Yuehan Ouyang,Xiyue Zheng,Xiaobang Chen,Zequan Lin,Ruitian Zhu,Lan Lan,Dongyang Qian,Rongrong Li,Jixiang Zhu,Yuanye Dang,Yan Wang,Sida Liao,Xiumei Tian,Fanwen Yang
Airway stenosis, a significant cause of dyspnea, is commonly managed with airway stents. However, conventional stents frequently lead to restenosis. Excessive proliferation of fibroblasts and smooth muscle cells during abnormal repair processes is a key factor in airway restenosis. To address this challenge, a novel drug-loaded airway stent has been designed with personalized tailoring for the patient. This stent features a three-layered structure: an outer layer made from a blend of thermoplastic polyurethane (TPU) and Poloxamer 407 (P407), a drug-loading intermediate layer, and an inner layer made of TPU. This design aims to minimize airway irritation and enable adjustable drug release rates by adjusting the drug carrier and/or the content of P407 in the stent’s outer layer. Drug release profile conforms to the Improved First-Order model. Notably, P407 is released from the stent, serving a dual purpose: it creates micropores to regulate the drug release rate and synergizes with PTX to inhibit the proliferation of fibroblasts. This combination significantly enhances the inhibitory effect on the proliferation of fibroblasts and smooth muscle cells, without adversely affecting airway epithelial cells. This may represent a novel approach to reducing restenosis by addressing a critical complication associated with the use of airway stents.
研究领域:
生物医学工程
·
药学
·
组织工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Feiran Zhou,Xinyi Hu,Weijing Feng,Minghui Li,Bin Yu,Chenxing Fu,Caiwen Ou
Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling . Curcumin , a traditional Chinese medicine , exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis.
研究领域:
分子生物学
·
药理学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）