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Materials Today Communications · 2025 · IF 4.5

Application of HMN-Cu2+ gel with anticoagulant function in promoting rapid vascular endothelial repair in blood fluid environment

Yi'an Chen,Mengxue Zhou,Jingyue Wang,Yunji Fei,Xiaoling Yan,Xin Hao,Ansha Zhao

Atherosclerotic plaques can be eliminated using approaches such as endarterectomy. However, intimal damage resulting from surgery is frequently challenging to address. Traditional surgical techniques often incorporate foreign substances such as modified stents or drugs to counter the consequences of intimal defects. Such treatment makes it difficult to repair vascular defects in endothelial segments. It is prone to cause problems such as hyperplasia and abnormal blood supply due to vascular endothelial defects. In this study, hyaluronic acid (HA), a natural extracellular mechanism component that is not prone to actively induce coagulation, was employed as a biomimetic material for intimal repair. Through chemical grafting modification, the gel was endowed with rapid photocuring performance within 3 s, and the scientific attributes of the gel-series materials were enhanced. The additional incorporation of Cu 2+ into the gel-prepared HMN-Cu 2+ hydrogel augmented the anticoagulant effect of the material while enhancing blood cell compatibility. The results of material science experiments indicate that HMN gel can adhere stably to various biological interfaces in a fluid environment mimicking blood flow, and its swelling and degradation properties are appropriate. Cell experiments and blood evaluation demonstrated that the gel exhibited favorable erythrocyte compatibility and anticoagulant and endothelial spreading capabilities during intimal repair. The gel has the potential to substitute the intima barrier, improve the intima repair environment, and facilitate subsequent intima repair. It can effectively resolve the problem of intima layer irreparability during novel low-damage vascular surgeries such as intima stripping and plaque rotation.

CAS / MDL: 68-04-2
研究领域: 生物材料学 · 医学工程 · 血管外科
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Acta Biomaterialia · 2025 · IF 9.6

PEGNB-Heparin-Liposome composite hydrogels for in situ spraying and ultra-fast adhesion: meeting the challenges of endothelial repair of vascular injury

Jiang Shao,Yanqiu Liu,Ruolan Li,Zengyi Deng,Luying Liu,Jingyue Wang,Sheng Dai,Zhaogui Su,Jiawei Cui,Yian Chen,Xiaoling Yan,Ping Yang,Manfred F Maitz,Ansha Zhao

Carotid atherosclerosis is an essential cause of transient cerebral ischemia, stroke, and other cerebrovascular diseases, and carotid endarterectomy (CEA) is currently the most effective treatment for removing plaque and restoring the vascular lumen. However, the CEA disrupts the integrity and functionality of the endothelium and predisposes it to complications such as restenosis and thrombosis. Hydrogels can closely mimic the natural extracellular matrix, allowing a wide tuning of physical and chemical properties. These properties make hydrogels the most promising candidate materials for the repair of vascular injured intima. In this study, a multifunctional intimal repair hydrogel of poly(ethylene glycol)-norbornene (PEGNB)/ Heparin/ Liposome is proposed with the advantages of ultra-rapid adhesion to the wet tissue of the vascular inner wall, maintenance of adhesion stability under continuous erosion by blood flow. The hydrogel was supplemented with poly(vinyl butyral) (PVB) to reduce its swelling rate, and Rapamycin (RAPA) was encapsulated in this study as the drug into the cationic liposomes. This composite multifunctional (PNHB@Lip(RAPA)) hydrogel has exhibited outstanding anti-coagulation properties, markedly suppressed the proliferation and migration of SMCs, and displayed favourable cytocompatibility and blood compatibility. Concurrently, the capacity of the PNHB@Lip(RAPA) hydrogel to stimulate endovascular regeneration and deter restenosis and thrombus formation was validated through carotid intima damage repair experiments. These findings collectively indicate that the PNHB@Lip(RAPA) hydrogel represents a promising material for intimal injury repair, offering innovative insights into intimal repair methodologies. Statement of Significance Carotid atherosclerosis is a leading cause of transient cerebral ischemia, stroke, and cerebrovascular disorders. Although carotid endarterectomy (CEA) effectively removes plaques, it damages endothelial integrity, increasing the risk of restenosis and thrombosis. To address this, we developed PNHB@Lip(RAPA), a multifunctional intimal repair hydrogel composed of PEGNB, heparin, and rapamycin-encapsulated liposomes. This hydrogel rapidly adheres to wet vascular walls, resists blood flow erosion, and exhibits low swelling. The hydrogel demonstrates superior anticoagulation, inhibits smooth muscle cell proliferation and migration, and shows favourable cytocompatibility. Experimental results confirm its ability to promote endovascular regeneration while preventing restenosis and thrombosis. In summary, PNHB@Lip(RAPA) hydrogel is a promising material for intimal repair, offering innovative solutions to improve CEA postoperative outcomes.

研究领域: 生物材料学 · 医学工程 · 血管生物学
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 22 ·4882-4889 · IF 7

A pDNA/rapamycin nanocomposite coating on interventional balloons for inhibiting neointimal hyperplasia

Yu-xian Lai,Jia-yin Fu,Shao-fei Wu,Ren-yun Li,Jia-qi Hu,You-xiang Wang,M. Cristina L. Martins,Ke-feng Ren,Jian Ji,Guo-sheng Fu

Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries.

CAS / MDL: 573-58-0 25535-16-4
研究领域: 心血管医学 · 药学 · 生物医学工程
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Small · 2021 ·Vol. 18 ·期 9 ·2104120 · IF 13.281

Multi-Pathway Microenvironment Regulation for Atherosclerosis Therapy Based on Beta-Cyclodextrin/L-Arginine/Au Nanomotors with Dual-Mode Propulsion

Ziyu Wu,Rui Wu,Xiaoyun Li,Xingwen Wang,Xueting Tang,Kaiyuan Tan,Mimi Wan,Chun Mao,Xingquan Xu,Huiming Jiang,Jiawei Li,Min Zhou,Dongquan Shi

Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of β-cyclodextrin (β-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and β-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.

研究领域: 纳米技术 · 生物医学工程 · 治疗学 · 心血管疾病
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