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1.
Adv Healthc Mater ; 12(30): e2300746, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37632326

RESUMO

There is an urgent need to develop a series of multifunctional materials with good biocompatibility, high mechanical strength, hemostatic properties, antiadhesion, and anti-infection for applications in wound care. However, successfully developing multifunctional materials is challenging. In this study, two superhydrophobic composite coatings with good biocompatibility, high mechanical strength, strong antifouling and blood repellency, fast hemostasis, and good antibacterial activity are prepared on cotton fabric surface by simple, green, and low-cost one-step dip-coating technology. The results discussed in the manuscript reveals that the two superhydrophobic composite coatings can maintain good mechanical stability, strong water repellency, and durability under various types of mechanical damage, high-temperature treatment, and long-term strong light irradiation. The coatings also exhibit good repellency to various solid pollutants, highly viscous liquid pollutants, and blood. In vitro and in vivo hemostatic experiments show that both composite coatings have good hemostatic and anticlot adhesion properties. More importantly, this superhydrophobic coating prevents bacterial adhesion and growth and released Cu2+ and Zn2+ ions and chitosan to achieve bactericidal properties, thereby protecting injured skin from bacterial infection. The two superhydrophobic coatings enhance the antifouling, antiadhesion, hemostatic, and antibacterial functions of blood-repellent dressings and therefore have broad application prospects in medical and textile fields.


Assuntos
Quitosana , Poluentes Ambientais , Hemostáticos , Interações Hidrofóbicas e Hidrofílicas , Antibacterianos/farmacologia , Antibacterianos/química , Zinco
2.
ACS Appl Mater Interfaces ; 15(1): 265-280, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36537551

RESUMO

Naked medical devices are often damaged by blood, bacteria, and other extreme environmental conditions (heat, humidity, acid, alkali, salts, and others), causing device failure and increasing difficulty for the operator. They can also cause inflammation and coagulation resulting in severe complications and even death. In this work, the superhydrophobic ZnO/copper-zinc metal-organic frameworks@stearic acid (ZnO/Cu-ZnMOFs@SA) composite coatings with hierarchical micro/nanostructures were fabricated on Zn substrates via a one-step hydrothermal method. The effects of hierarchical micro/nanostructures on surface wettability, physicochemical stability, and biological properties have been studied in this manuscript. The structure not only provided the coatings with robust waterproofing, abrasive resistance, durability, and thermal and light irradiation stability but also successfully recovered their superhydrophobicity by remodifying the surface with SA, showing excellent repeatability. In addition, the coating demonstrates excellent corrosion resistance and self-cleaning ability and rejects various solid and liquid contaminants. The superhydrophobic ZnO/Cu-ZnMOFs@SA composite coatings also exhibited excellent antibacterial and thrombosis resistance. The findings indicated that the superhydrophobic composite coatings have a strong potential for application in medical instruments for exhibiting multifunctional properties in various extreme environments.


Assuntos
Nanoestruturas , Óxido de Zinco , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Nanoestruturas/química , Molhabilidade , Antibacterianos/farmacologia , Antibacterianos/química , Coagulação Sanguínea
3.
Curr Med Chem ; 30(31): 3582-3613, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36306453

RESUMO

Atherosclerosis is a multifactorial result of complicated pathophysiology. Changes in the expression of polygenes, coupled with environmental and lifestyle factors, trigger a cascade of adverse events involving a variety of cell types, such as vascular endothelial cells, smooth muscle cells, and macrophages. In this review, we summarize the function and therapeutic targets of atherosclerotic cells. This article reviews the role of endothelial cells, smooth muscle cells, macrophages and foam cells in the development of atherosclerosis and the progress in the treatment of atherosclerosis by targeting these cells. Atherosclerotic plaque involves a variety of cells and biomolecules, and its complex biological environment is a difficult point for the study and treatment of atherosclerosis. For treating atherosclerosis, a large number of studies emerged based on blocking or inhibiting factors affecting the formation and development of plaque. Cardiovascular stent intervention is currently the main method for the treatment of atherosclerosis. In recent decades, numerous studies on cardiovascular, stents mainly involve drug coating or biomolecular modification of stents to enhance anti-thrombosis, anti-restenosis and endothelialization. This paper introduces the research status of cardiovascular stents and new strategies for surface modification. The treatment of atherosclerosis based on the level of molecular biology and cell biology is becoming a research hotspot in the coming decades.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/terapia , Placa Aterosclerótica/etiologia , Células Endoteliais/metabolismo , Aterosclerose/terapia , Aterosclerose/metabolismo , Stents/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos
4.
Biomater Sci ; 11(1): 322-338, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36448996

RESUMO

The anticoagulation and antibacterial functions of implant and interventional catheters during indwelling will determine their success or failure. Here, an amino-containing copper-based metal-organic framework (Cu-MOF) coating was prepared on the thermoplastic polyurethane substrate (TPU) surface by spin coating for anti-thrombotic and anti-infection effects. The adhesion properties of the polyurethane prepolymer coating (PC) enhanced the binding force of Cu-MOF particles and TPU surface and improved stability. Due to the coordination affinity of Cu2+ with nitric oxide (NO) and the NO loading capacity of the amino group, it showed that a large amount of NO was loaded in the coating. Meanwhile, the coordinated Cu2+ in the coating also catalyzed endogenous NO donors to generate NO, which prolonged the NO release for up to 30 days. The results of antibacterial experiments showed that the NO released from the coating had good antibacterial effects on both E. coli and S. epidermidis. An obvious antibacterial ring can be seen and the antibacterial rate was higher than 96%. It also showed inhibiting platelet adhesion and activation, prolonged in vitro clotting time and inhibited thrombus formation. In summary, for the first time, NO release from the coating was realized by the combined ways of NO donor and catalytic endogenous NO donor. It can not only meet the high NO release rate required for early anticoagulation and antibacterial of the catheter but also maintain normal anticoagulation requirements in the later period.


Assuntos
Escherichia coli , Óxido Nítrico , Óxido Nítrico/química , Poliuretanos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Anticoagulantes/farmacologia , Cobre/farmacologia , Cobre/química
5.
ACS Biomater Sci Eng ; 8(11): 4777-4788, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36256970

RESUMO

Carbon monoxide (CO) is a bioactive molecule with high potential as it shows promising efficacy for regulating inflammation. Materials capable of storing and delivering CO are of great potential therapeutic value. Although CO-releasing molecules (CORMs) have been developed to deliver CO, the short CO duration of minutes to 2 h confines their practical use. In this study, partially reduced MIL-100(Fe) as a new CO-releasing nanoMOF was developed and used for sustained CO release and macrophage (MA) phenotypic polarization regulation. MIL-100(Fe) was synthesized and mildly annealed in vacuum for partial reduction. When the annealing temperature was lower than 250 °C, less Fe(II) present in MIL-100(Fe) and the subsequent CO adsorption and desorption profiles displayed typical features of physisorption. While it was annealed at 250 °C, it showed about 20% of Fe(III) was reduced, which resulted in chemisorption of CO due to the high coordination affinity of Fe(II) to CO. The loading amount of CO was increased, and the CO release was prolonged for about 24 h. Furthermore, the CO release from this nanoMOF could alter the lipopolysaccharide (LPS)-induced macrophage from M1 to the alternative M2 phenotype and promoted the growth of endothelial cells (ECs) by paracrine regulation of MA. It can be envisioned as a promising CO-releasing solid for biomedical application.


Assuntos
Células Endoteliais , Compostos Férricos , Compostos Ferrosos/farmacologia , Macrófagos , Fenótipo
6.
Mol Pharm ; 19(12): 4685-4695, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36278815

RESUMO

Surface modification manipulates the application performance of materials, and thrombosis caused by material contact is a key risk factor of biomaterials failure in blood-contacting/implanting devices. Therefore, building a safe and effective hemocompatibility platform is still urgent. Owing to the unique properties of polyamidoamine (PAMAM) dendrimers, in this study, modified surfaces with varying dendrimer densities were interacted with elements maintaining blood homeostasis. These included the plasma proteins bovine serum albumin and fibrinogen, cells in blood (platelets and erythrocyte), as well as endothelial cells (ECs), and the objective was to evaluate the blood compatibility of the chosen materials. Whole blood test and dynamic blood circulation experiment by the arteriovenous shunt mode of rabbit were also conducted, based on the complexity and fluidity of blood. The PAMAM-modified substrates, particularly that with a high density of PAMAM (N1.0), adsorbed proteins with lessened fibrinogen adsorption, reduced platelet activation and aggregation, and suppressed clotting in whole blood and dynamic blood testing. Furthermore, the designed PAMAM dendrimer densities were safe and showed negligible erythrocyte lysis. Concurrently, PAMAM modification could maintain EC growth and did not trigger the release of procoagulant factors. These results suggest that the PAMAM-modified materials are compatible for maintaining blood homeostasis. Thus, PAMAM dendrimers can work as excellent surface modifiers for constructing a hemocompatibility platform and even a primer layer for desired functional design, promoting the service performance of blood-contacting devices.


Assuntos
Dendrímeros , Animais , Coelhos , Dendrímeros/química , Células Endoteliais/metabolismo , Diálise Renal , Fibrinogênio
7.
J Appl Biomater Funct Mater ; 20: 22808000221105332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35666145

RESUMO

In recent years, more and more metal or non-metal materials have been used in the treatment of cardiovascular diseases, but the vascular complications after transplantation are still the main factors restricting the clinical application of most grafts, such as acute thrombosis and graft restenosis. Implant materials have been extensively designed and surface optimized by researchers, but it is still too difficult to avoid complications. Natural vascular endodermis has excellent function, anti-coagulant and anti-intimal hyperplasia, and it is also the key to maintaining the homeostasis of normal vascular microenvironment. Therefore, how to promote the adhesion of endothelial cells (ECs) on the surface of cardiovascular materials to achieve endothelialization of the surface is the key to overcoming the complications after implant materialization. At present, the surface endothelialization design of materials based on materials surface science, bioactive molecules, and biological function intervention and feedback has attracted much attention. In this review, we summarize the related research on the surface modification of materials by endothelialization in recent years, and analyze the advantages and challenges of current endothelialization design ideas, explain the relationship between materials, cells, and vascular remodeling in order to find a more ideal endothelialization surface modification strategy for future researchers to meet the requirements of clinical biocompatibility of cardiovascular materials.


Assuntos
Prótese Vascular , Células Endoteliais , Materiais Biocompatíveis , Endotélio Vascular , Humanos
8.
Int J Mol Sci ; 23(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563532

RESUMO

Vascular stent service involves complex service environments and performance requirements, among which the histocompatibility of the stent could seriously affect the therapeutic effect. In the pathology of vascular disease, the thin fiber cap is easily ruptured, exposing the necrotic core below, and triggering a series of dangerous biochemical reactions. In contrast, the thin neointima, considered an essential structure growing on the stent, may evolve into vulnerable plaque structures due to lesions induced by the stent. Therefore, the reduction of necrosis around the stent below the thin neointima is indispensable. In this work, different cell model experiments suggested that the content of endogenous labile Zn positively correlated with cell injury. Zinquin-Zn fluorescence experiments and zinc ion channels research suggested that the change in the content of endogenous labile Zn in smooth muscle cells is affected by different stent coatings. The content of endogenous labile Zn in cells negatively correlated with cell viability. Animal experiments indirectly verified the increase in endogenous labile Zn by detecting the expression of Zn regulatory protein (metallothionein) in the necrotic tissues. Reducing the content of endogenous labile Zn may favor a reduction in smooth muscle cell injury and necrosis. This biochemical mechanism is effective in improving the therapeutic effect of vascular stents.


Assuntos
Miócitos de Músculo Liso , Neointima , Animais , Miócitos de Músculo Liso/metabolismo , Necrose/metabolismo , Neointima/metabolismo , Stents , Zinco/metabolismo
9.
Macromol Biosci ; 22(8): e2200019, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35598070

RESUMO

Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both the structure and functions of natural ECM remain a challenge. Self-assembling peptide RADA16 nanofiber has distinct advantages to provide a biomimetic extracellular matrix nanofiber structure. However, it still lacks biological cues to promote angiogenesis that is of vital significance for diabetic wound healing. With a customized copper peptide glycyl-histidyl-lysine (GHK) functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, is innovatively proposed in this present study. The acquired composite hydrogel holds the biomimetic nanofiber architecture, and exhibits promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It shows that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis give evidence that an upregulated expression of eNOS and CD31 in the copper peptide-functionalized RADA16 treated group. It can be envisioned that this scaffold can serve as a promising dressing for diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Nanofibras , Animais , Biomimética , Cobre/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Células Endoteliais/metabolismo , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Nanofibras/química , Peptídeos/química , Alicerces Teciduais/química , Cicatrização
10.
RSC Adv ; 12(4): 2383-2390, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35425263

RESUMO

Nitric oxide (NO) shows high potential in the cardiovascular system with anticoagulant and antibacterial efficacy. Cu based metal organic frameworks with amino modification (CuMOFs) were found to have an extraordinary high NO loading, but at the expense of framework stability in ambient moisture. Nano CuMOFs was synthesized by hydrothermal method in this work, and treated with stearic acid (SA) creating a hydrophobic form. It was found that the structure of the particles was not affected after treatment with SA, and the treated CuMOFs had tunable hydrophobicity. Both CuMOFs and SA modified CuMOFs adsorbed NO with the reaction of the amino group and NO to form a NONOate. SA modification enhanced stability of the CuMOFs in phosphate buffer solution (PBS, pH = 7.4), slowed down the interaction between the NO loading unit and H2O, and thus NO releasing was prolonged. The resulting NO-loaded CuMOFs inhibited platelet activation dramatically, prolonged the coagulation time and displayed excellent antibacterial properties. They could be envisioned as a good candidate for application in blood contacting implants.

11.
J Tissue Eng ; 13: 20417314221088509, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356091

RESUMO

Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.

12.
Int J Mol Sci ; 23(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163172

RESUMO

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60 µm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.


Assuntos
Antígenos CD/farmacologia , Caderinas/farmacologia , Fatores de Crescimento de Fibroblastos/farmacologia , Pele/metabolismo , Alginatos/química , Animais , Antibacterianos/química , Curativos Hidrocoloides , Linhagem Celular , China , Quitosana/química , Hemostáticos/química , Hidrogéis/síntese química , Hidrogéis/química , Masculino , Coelhos , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Cicatrização/fisiologia
13.
Curr Drug Deliv ; 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234105

RESUMO

The article has been withdrawn at the request of the editor of the journal Current Drug Delivery due to incoherent content.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

14.
J Biomed Mater Res A ; 108(6): 1295-1304, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32064767

RESUMO

The rapid re-endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF-loaded heparin/poly-l-lysine (Hep-PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF-loaded nanoparticles were immobilized on dopamine-coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF-loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep-PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.


Assuntos
Anticoagulantes/química , Materiais Revestidos Biocompatíveis/química , Stents Farmacológicos , Heparina/química , Polilisina/química , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Anticoagulantes/farmacologia , Plaquetas/efeitos dos fármacos , Linhagem Celular , Materiais Revestidos Biocompatíveis/farmacologia , Heparina/farmacologia , Humanos , Teste de Materiais , Nanopartículas/química , Adesividade Plaquetária/efeitos dos fármacos , Polilisina/farmacologia , Aço Inoxidável/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/farmacologia
15.
Colloids Surf B Biointerfaces ; 180: 168-176, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31048242

RESUMO

Due to their relatively good biocompatibility and inactivity, titanium oxide films (Ti-O) are used in the coating of coronary stents, which reduces metal corrosion, slows metal ion release, and improves endothelial cell (EC) compatibility. Here, we report further functionalizing Ti-O with biological cues for selective endothelialization. Selenocystine with an l- or a d-enantiomer was first immobilized on the Ti-O film via polydopamine to generate nitric oxide (NO) endogenously, which inhibited smooth muscle cell (SMC) proliferation, followed by the grafting of a functional KREDVC peptide to induce EC adhesion. The synergistic effects of the immobilized KREDVC, surface chirality, and NO generation on selective endothelialization were investigated. The results showed that the surface chirality of the l-enantiomer and KREDVC grafting significantly enhanced the attachment and growth of ECs compared to SMCs. An in vivo study showed von Willebrand factor expression was increased and neointimal hyperplasia was significantly decreased in samples with l-selenocystine immobilization and KREDVC grafting. In summary, these findings provide new insights on the surface modification of cardiovascular implants with selective endothelialization.


Assuntos
Cistina/análogos & derivados , Hiperplasia/prevenção & controle , Indóis/química , Neointima/prevenção & controle , Oligopeptídeos/química , Compostos Organosselênicos/química , Polímeros/química , Titânio/química , Animais , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Cistina/química , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hiperplasia/etiologia , Hiperplasia/metabolismo , Hiperplasia/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Neointima/etiologia , Neointima/metabolismo , Neointima/patologia , Óxido Nítrico/biossíntese , Óxido Nítrico/farmacologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Titânio/farmacologia , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismo
16.
Biomaterials ; 204: 36-45, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30875517

RESUMO

In-stent restenosis is worsened by thrombosis, acute inflammation, and uncontrollable smooth muscle cells (SMCs) proliferation at the early stage of implantation. Tailoring the stent surface can inhibit thrombosis, intimal hyperplasia, and accelerate re-endothelialization. In situ nitric oxide (NO) generation is considered as a promising method to improve anti-coagulation and anti-hyperplasia abilities. Copper based metal organic frameworks showed great potential as catalysts for NO generation, and copper ion (Cu2+) was demonstrated to promote endothelial cells (ECs) growth. Herein, by using polydopamine as the linker and coating matrix, nanoscale copper-based metal organic frameworks (nano Cu-MOFs) were immobilized onto the titanium surface for simultaneous nitric oxide (NO) catalytic generation and Cu2+ delivery. The nano Cu-MOFs-immobilized coating exhibited desirable NO release and adaptable Cu2+ delivery. Such coating inhibited platelet aggregation and activation via NO-cGMP signaling pathway, and significantly reduced thrombosis in an ex vivo extracorporeal circulation model. NO release and Cu2+ delivery showed synergetic effect to promote EC proliferation. Moreover, SMCs and macrophage proliferation was suppressed by the nano Cu-MOFs-immobilized coating, thereby reducing neointimal hyperplasia in vivo. Overall, this biocompatible coating is convenient for the surface modification of cardiovascular stents and effectively prevents the late stent thrombosis and in-stent restenosis associated with stent implantation.


Assuntos
Sistema Cardiovascular/patologia , Materiais Revestidos Biocompatíveis/química , Cobre/química , Gasotransmissores/análise , Indóis/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Polímeros/química , Stents , Animais , Proliferação de Células , GMP Cíclico/metabolismo , Células Endoteliais/citologia , Humanos , Implantes Experimentais , Masculino , Estruturas Metalorgânicas/ultraestrutura , Camundongos , Miócitos de Músculo Liso/citologia , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Ativação Plaquetária , Adesividade Plaquetária , Células RAW 264.7 , Coelhos , Ratos Sprague-Dawley
17.
ACS Appl Mater Interfaces ; 11(8): 7872-7883, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30726055

RESUMO

A coating that can generate nitric oxide (NO) for surface modification of cardiovascular stents with adaptable NO release is an efficient approach to prevent thrombosis and neointimal hyperplasia. Herein, we prepared a copper-based surface-attached metal-organic framework (Cu-SURMOFs) of copper(II) benzene-1,3,5-tricarboxylate (CuBTC) using a layer-by-layer assembly method (LBL) for NO generation on the surface of alkali-activated titanium. It was easy to control surface chemistry and NO release by changing the number of LBL deposition cycles. The obtained CuBTC coating was characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy analysis and was able to decompose endogenous S-nitrosoglutathoine (GSNO) to catalytically produce NO. The resulting NO flux increased with increased deposition cycles. The coating prepared with 10 cycles of deposition showed ideal NO release and promoted proliferation of endothelial cells, suppressed growth of smooth muscle cells and macrophages, and inhibited platelet adhesion and activation. Further evaluation of thrombogenicity in an arteriovenous shunt model showed that the CuBTC coating had great ability to prevent thrombosis, and in vivo implantation of CuBTC-coated titanium wire demonstrated a significant inhibition of intimal hyperplasia. The results showed that use of copper-based SURMOFs could be a promising strategy for the surface modification of cardiovascular stents.


Assuntos
Materiais Biocompatíveis/química , Cobre/química , Estruturas Metalorgânicas/química , Óxido Nítrico/metabolismo , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Catálise , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Hemoglobinas/química , Humanos , Masculino , Camundongos , Neointima/terapia , Agregação Plaquetária/efeitos dos fármacos , Próteses e Implantes , Coelhos , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Ácidos Tricarboxílicos/química
18.
Langmuir ; 33(39): 10402-10410, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28885030

RESUMO

Adsorbed proteins and their conformational change on blood-contacting biomaterials will determine their final hemocompatibility. It has frequently been reported that surface chirality of biomaterials may highly influence their protein adsorption behavior. Here, lysine and tartaric acid with different chirality were immobilized onto TiO2 films respectively, and the influence of surface chirality on protein adsorption, platelet adhesion, and activation was also investigated. It showed that the l- and d-molecule grafted samples had almost the same grafting density, surface topography, chemical components, and hydrophilicity in this study. However, biological behaviors such as protein adsorption, platelet adhesion, and activation were quite different. The d-lysine grafted surface had a greater ability to inhibit both bovine serum albumin and fibrinogen adsorption, along with less degeneration of fibrinogen compared to the l-lysine anchored surface. However, the d-tartaric acid grafted surface adsorbed more protein but with less denatured fibrinogen compared to the l-tartaric acid grafted one. Further studies showed that the secondary structural change of the adsorbed albumin and fibrinogen on all surfaces with deduction of the α-helix content and increase of disordered structure, while the changing degree was apparently varied. As a result, the d-lysine immobilized surface absorbed less platelets and red blood cells and achieved slightly increased platelet activation. For tartaric acid anchored surfaces, a larger number of platelets adhered to the D-surface but were less activated compared to the L-surface. In conclusion, the surface chirality significantly influenced the adsorption and conformational change of blood plasma protein, which in turn influenced both platelet adhesion and activation.


Assuntos
Adesividade Plaquetária , Adsorção , Materiais Biocompatíveis , Plaquetas , Fibrinogênio , Ativação Plaquetária , Propriedades de Superfície
19.
Colloids Surf B Biointerfaces ; 145: 122-129, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27153116

RESUMO

As nitric oxide (NO) plays vital roles in the cardiovascular system, incorporating this molecule into cardiovascular stents is considered as an effective method. In the present study, selenocystine with different chirality (i.e., l- and d-selenocystine) was used as the catalytic molecule immobilized on TiO2 films for decomposing endogenous NO donor. The influences of surface chirality on NO release and platelet behavior were evaluated. Results show that although the amount of immobilized l-selenocystine on the surface was nearly the same as that of immobilized d-selenocystine, in vitro catalytic NO release tests showed that l-selenocystine immobilized surfaces were more capable of catalyzing the decomposition of S-nitrosoglutathione and thus generating more NO. Accordingly, l-selenocystine immobilized surfaces demonstrated significantly increased inhibiting effects on the platelet adhesion and activation, when compared to d-selenocystine immobilized ones. Measurement of the cGMP concentration of platelets further confirmed that surface chirality played an important role in regulating NO generation and platelet behaviors. Additionally, using bovine serum albumin and fibrinogen as model proteins, the protein adsorption determined with quartz crystal microbalance showed that the l-selenocystine immobilized surface enhanced protein adsorption. In conclusion, surface chirality significantly influences protein adsorption and NO release, which may have significant implications in the design of NO-generating cardiovascular stents.


Assuntos
Plaquetas/efeitos dos fármacos , Cistina/análogos & derivados , Óxido Nítrico/metabolismo , Compostos Organosselênicos/química , Titânio/química , Células A549 , Animais , Catálise , Bovinos , Cistina/química , Fibrinogênio/química , Ativação Plaquetária , Soroalbumina Bovina/química
20.
Biomaterials ; 63: 80-92, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26093790

RESUMO

The continuous release of nitric oxide (NO) by the native endothelium of blood vessels plays a substantial role in the cardiovascular physiology, as it influences important pathways of cardiovascular homeostasis, inhibits vascular smooth muscle cell (VSMC) proliferation, inhibits platelet activation and aggregation, and prevents atherosclerosis. In this study, a NO-catalytic bioactive coating that mimics this endothelium functionality was presented as a hemocompatible coating with potential to improve the biocompatibility of vascular stents. The NO-catalytic bioactive coating was obtained by covalent conjugation of 3,3-diselenodipropionic acid (SeDPA) with glutathione peroxidase (GPx)-like catalytic activity to generate NO from S-nitrosothiols (RSNOs) via specific catalytic reaction. The SeDPA was immobilized to an amine bearing plasma polymerized allylamine (PPAam) surface (SeDPA-PPAam). It showed long-term and continuous ability to catalytically decompose endogenous RSNO and generate NO. The generated NO remarkably increased the cGMP synthesis both in platelets and human umbilical artery smooth muscle cells (HUASMCs). The surface exhibited a remarkable suppression of collagen-induced platelet activation and aggregation. It suppressed the adhesion, proliferation and migration of HUASMCs. Additionally, it was found that the NO catalytic surface significantly enhanced human umbilical vein endothelial cell (HUVEC) adhesion, proliferation and migration. The in vivo results indicated that the NO catalytic surface created a favorable microenvironment of competitive growth of HUVECs over HUASMCs for promoting re-endothelialization and reducing restenosis of stents in vivo.


Assuntos
Materiais Revestidos Biocompatíveis/metabolismo , Glutationa Peroxidase/metabolismo , Óxido Nítrico/administração & dosagem , Propionatos/metabolismo , S-Nitrosotióis/metabolismo , Compostos de Selênio/metabolismo , Stents , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Endotélio/metabolismo , Glutationa Peroxidase/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Propionatos/química , Coelhos , Compostos de Selênio/química
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