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Abstract: Poor haemocompatibility is a main issue of artificial cardiovascular materials in clinical application. Nitric oxide (NO), produced by vascular endothelial cells, is a well known inhibitor of platelet adhesion and activation. Thus, NO-releasing biomaterials are beneficial for improving haemocompatibility of blood-contacting biomedical devices. In this paper, a novel method was developed for enhancement of haemocompatibility by exploiting endogenous NO donors. TiO2 films were firstly synthesized on Si (100) wafers via unbalanced magnetron sputtering technology, and then polydopamine was grafted on TiO2 films and used as a linker for further immobilization of cystamine. The obtained surfaces were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. NO generation is evaluated by saville-griess reagents, and it shows that cystamine immobilized samples are able to catalytically generate NO by decomposing endogenous S-nitrosothiols (RSNO). In vitro platelet adhesion results reveal that cystamine modified surfaces can inhibit collagen-induced platelet activation. ELISA analysis reveals that cGMP in platelets obviously increases on cystamine immobilized surface, which suggests the reducing of platelet activation is through NO/cGMP signal channel. It can be concluded that cystamine immobilized surface shows better blood compatibility by catalyzing NO release from the endogenous NO donor. It may be a promising method for improvement of haemocompatibility of blood-contacting implants. [Copyright &y& Elsevier]

Abstract: Immobilization of selenocystamine on TiO2 film deposited on silicon wafer and 316 stainless steel stents for catalytic generation of nitric oxide was described. Polydopamine was used as the linker for immobilization of selenocystamine to the TiO2 surface. In vitro stability of the immobilized selenocystamine was investigated and the result shows surface selenium loss occurs mostly in the first four weeks. The selenocystamine immobilized surface possesses glutathione peroxidase (GPx) activity, and the activity increases with the amount of grafted polydopamine. Such selenocystamine immobilized surfaces show the ability of catalytically decomposing endogenous S-nitrosothiols (RSNO), generating NO; thus the surface displays the ability to inhibit collagen-induced platelet acitivation and aggregation. Additionally, smooth muscle cells are inhibited from adhering to the selenocystamine immobilized sample when RSNO is added to the culture media. ELISA analysis reveals that cGMP in both platelets and smooth muscle cells significantly increases with NO release on selenocystamine immobilized samples. Two months in vivo results show that selenocystamine immobilized stents are endothelialized, and show significant anti-proliferation properties, indicating that this is a favorable method for potential application in vascular stents. [ABSTRACT FROM AUTHOR]

Because preparation circumstances are limited, the relationship between spherical porous zinc sulfide (ZnS) and cells is rarely investigated. Thus, using the hydrothermal approach, four different types of ZnS spheres with consistent size, high dispersion, and stability were created in this research by varying the temperature, duration, solvent ratio, and pH level of the hydrothermal process. Three structures are present in the generated particle spheres: solid, hollow, and mesoporous structures. In addition to causing a significant variation in the particle spheres' specific surface area, porosity, and surface roughness, the distinct architectures also have an impact on ZnS particle spheres' capacity to produce hydrogen sulfide (H 2 S) gas in an acidic environment. Experiments on hemolysis and cytotoxicity demonstrated that ZnS particle spheres with varying concentrations and shapes exhibited no cytotoxicity and good biocompatibility. According to cellular uptake trials, ZnS particle spheres with a rougher surface structure and a bigger specific surface area are more likely to be absorbed by macrophages and release more H 2 S gas. This activity of releasing H 2 S gas by H+ action and MA phagocytosis by employing ZnS as a donor lays the groundwork for later particles to load medicines and carry out biological functions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the cardiovascular system, endothelial cells play an important role in maintaining the steady state of the vascular environment and are the key to repairing damaged blood vessels. Magnetic ferroferric oxide nanoparticles (Fe3O4-NP) have good magnetic targeting and attract much attention in the field of biomaterials. However, poor cell compatibility severely limits its application in the field of cardiovascular and endothelial cell therapy. In this study, through surface modification of Fe3O4-NP, CAG peptides with good affinity for endothelial cells were introduced to the surface of nanoparticles to obtain functionalized Fe3O4-CAG nanoparticles so as to improve the cell compatibility of nanoparticles. The results showed that the dispersion of Fe3O4-CAG particles was improved and the magnetic properties were reduced. The activity of endothelial cells could be enhanced and the proliferation rate could be increased by 187.4%. Under the action of an external magnetic field, the endothelial cells could be induced to migrate directionally and the migration distance increased by 33.5%. The results of this study indicate that by modifying CAG polypeptide on the surface of Fe3O4-NP, it provided a new method for its research and application in the cardiovascular system and vascular repair. [ABSTRACT FROM AUTHOR]

• l / d -selenocystine was immobilized on the Ti-O film, followed by grafting of KREDVC. • l -selenocystine and KREDVC immobilization enhanced attachment and growth of ECs. • Endothelialization was enhanced and neointimal hyperplasia was decreased in vivo. 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 i n 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. [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical abstract A nano Cu-MOFs-immobilized coating for surface modification of cardiovascular stents to release NO and deliver copper ion is developed. Such coating exhibits adaptable, steady NO release and desirable copper ion delivery. The stents modified by this coating showed synergy effect on inhibiting platelet adhesion and activation, promoting endothelialization, suppressing intimal hyperplasia and regulating immune response to reduce LST and ISR for cardiovascular applications. Image 1 [ABSTRACT FROM AUTHOR]

Nitric Oxide (NO) generation from endogenous NO-donors catalyzed by diselenide modified biomaterials has been reported. Here we reported surface chirality by L-tartaric acid and D-tartaric acid grafting on the outermost showed a significant impact on diselenide modified biomaterials, which modulated protein adsorption, NO release and anti-platelet adhesion properties. D-tartaric acid grafted surface showed more blood protein adsorption than that of L-surfaces by QCM analysis, however, ELISA analysis disclosed less fibrinogen denatured on the D surfaces. Due to the surface ratio of selenium decreasing, NO release catalyzed by L-tartaric acid grafting on the outermost significantly decreased in comparison to that of only selenocystamine immobilized surfaces. While NO release catalyzed by D-tartaric acid grafting on the outermost didn’t decrease and was similar with that of selenocystamine immobilized surfaces. Surface chirality combined with NO release had synergetic effects on platelet adhesion, and it showed the lowest number of platelets adhered on the D-tartaric acid grafted surfaces. Thus surface chirality from D-tartaric acid grafting enhanced hemocompatibility of the surface in this study. Our work provides new insights into engineering novel blood contacting biomaterials by taking into account surface chirality. [ABSTRACT FROM AUTHOR]

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 TiO 2 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. [ABSTRACT FROM AUTHOR]

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 . [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Polydopamine (PDA), a bio-inspired polymer, has been very attractive for diverse functional applications by immobilizing biomolecules. In this work, a novel approach of using PDA for improved biomolecule immobilization was developed. A thin PDA layer was strategically coated onto 316L stainless steel and thermally treated at 150°C (PDA-Th150). Subsequently, amino-terminated polyethylene glycol (mPEG-NH2) or vascular endothelial growth factor (VEGF) was immobilized onto PDA and PDA-Th150 surface. The results of attenuated total reflection-Fourier transform-infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) showed higher coverage of quinine on PDA-Th150 surface. The functionalized PDA-Th150 significantly improved its ability of immobilizing mPEG-NH2 or VEGF, as shown by platelet adhesion test and endothelial cell proliferation experiments. This novel approach may also be used for efficient immobilization of biomolecules on different metal devices. [Copyright &y& Elsevier]