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CORM-401
Coatings · 2024 ·Vol. 14 ·期 11 ·1418 · IF 2.9

Construction of a Carbon Monoxide-Releasing Bioactive Hydrogel Coating on the Magnesium Alloy Surface for Better Corrosion Resistance, Anticoagulant Properties, and Endothelial Cell Growth

Renwei Gao,Lingjie Meng,Changjiang Pan

In this study, we first fabricated a crosslinked hydrogel coating by polymerizing methacryloyloxyethyl sulfonyl betaine and acrylamide (SBMA) on the magnesium (Mg) alloy surface employing ultraviolet (UV) polymerization. Bivalirudin and CO-releasing molecules (CORM-401) were further grafted onto the hydrogel coating surface to acquire a multifunctional biocompatible coating capable of releasing CO to augment corrosion-resisting properties and biocompatibility. The findings verified that the bioactive hydrogel coating significantly increased the corrosion potential and reduced the corrosion current, thereby improving the anticorrosion performance. Meanwhile, owing to the excellent hydrophilicity, the antifouling performance of the hydrogel coating, and the excellent anticoagulant performance of bivalirudin, the hydrogel coating significantly reduced the fibrinogen adsorption, platelet adhesion and activation, and hemolysis occurrence, displaying excellent ability to inhibit blood clotting. Moreover, endothelial cell (EC) experimental results demonstrated that the hydrogel coating could significantly promote EC growth, displaying great potential to induce re-endothelialization after implantation. Specifically, in the presence of cysteine capable of catalyzing CO release, the anticoagulant performance and ability to promote EC growth were further improved significantly. Therefore, the study offers an effective strategy to prepare a hydrogel coating capable of releasing CO to improve the corrosion-resisting performance and biocompatibility of Mg alloys, which is anticipated to be applied in the surface modification of Mg alloy intravascular stents.

研究领域: 材料科学 · 生物医学工程 · 表面化学 · 组织工程
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BIOMATERIALS · 2020 · IF 10.317

A multifunctional anti-inflammatory drug that can specifically target activated macrophages, massively deplete intracellular H2O2, and produce large amounts CO for a highly efficient treatment of osteoarthritis

Guangzhen Yang,Mengni Fan,Jingwu Zhu,Chen Ling,Lihuang Wu,Xin Zhang,Ming Zhang,Jiayi Li,Qingqiang Yao,Zhongwei Gu,Xiaojun Cai

Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2 . The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation ; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK , NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment.

CAS / MDL: 59-30-3 305-53-3
研究领域: 药理学 · 炎症 · 纳米技术 · 骨科 · 药物递送系统
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Biomaterials Advances · 2023 · IF 0

Fabrication of CO-releasing surface to enhance the blood compatibility and endothelialization of TiO2 nanotubes on titanium surface

Wenfu Ma,Xuhui Liu,Minhui Yang,Qingxiang Hong,Lingjie Meng,Qiuyang Zhang,Jie Chen,Changjiang Pan

Although the construction of nanotube arrays with the micro-nano structures on the titanium surfaces has demonstrated a great promise in the field of blood-contacting materials and devices, the limited surface hemocompatibility and delayed endothelial healing should be further improved. Carbon monoxide (CO) gas signaling molecule within the physiological concentrations has excellent anticoagulation and the ability to promote endothelial growth, exhibiting the great potential for the blood-contact biomaterials, especially the cardiovascular devices. In this study, the regular titanium dioxide nanotube arrays were firstly prepared in situ on the titanium surface by anodic oxidation, followed by the immobilization of the complex of sodium alginate/carboxymethyl chitosan (SA/CS) on the self-assembled modified nanotube surface, the CO-releasing molecule (CORM-401) was finally grafted onto the surface to create a CO-releasing bioactive surface to enhance the biocompatibility. The results of scanning electron microscopy (SEM), X-ray energy dispersion spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) revealed that the CO-releasing molecules were successfully immobilized on the surface. The modified nanotube arrays not only exhibited excellent hydrophilicity but also could slowly release CO gas molecules, and the amount of CO release increased when cysteine was added. Furthermore, the nanotube array can promote albumin adsorption while inhibit fibrinogen adsorption to some extent, demonstrating its selective albumin adsorption; although this effect was somewhat reduced by the introduction of CORM-401, it can be significantly enhanced by the catalytic release of CO. The results of hemocompatibility and endothelial cell growth behaviors showed that, as compared with the CORM-401 modified sample, although the SA/CS-modified sample had better biocompatibility, in the case of cysteine-catalyzed CO release, the released CO could not only reduce the platelet adhesion and activation as well as hemolysis rate, but also promote endothelial cell adhesion and proliferation as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression. As a result, the research of the present study demonstrated that the releasing CO from TiO 2 nanotubes can simultaneously enhance the surface hemocompatibility and endothelialization, which could open a new route to enhance the biocompatibility of the blood-contacting materials and devices, such as the artificial heart valve and cardiovascular stents.

研究领域: 生物材料学 · 医学工程
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