Catalytic Generation Of Nitric Oxide Research Articles

Mixed Metal-Organic Framework Mixed-Matrix Membranes: Insights into Simultaneous Moisture-Triggered and Catalytic Delivery of Nitric Oxide using Cryo-scanning Electron Microscopy.

The fundamental chemical and structural diversity of metal-organic frameworks (MOFs) is vast, but there is a lack of industrial adoption of these extremely versatile compounds. To bridge the gap between basic research and industry, MOF powders must be formulated into more application-relevant shapes and/or composites. Successful incorporation of varying ratios of two different MOFs, CPO-27-Ni and CuBTTri, in a thin polymer film represents an important step toward the development of mixed MOF mixed-matrix membranes. To gain insight into the distribution of the two different MOFs in the polymer, we report their investigation by Cryo-scanning electron microscopy (Cryo-SEM) tomography, which minimizes surface charging and electron beam-induced damage. Because the MOFs are based on two different metal ions, Ni and Cu, the elemental maps of the MOF composite cross sections clearly identify the size and location of each MOF in the reconstructed 3D model. The tomography run was about six times faster than conventional focused ion beam (FIB)-SEM and the first insights to image segmentation combined with machine learning could be achieved. To verify that the MOF composites combined the benefits of rapid moisture-triggered release of nitric oxide (NO) from CPO-27-Ni with the continuous catalytic generation of NO from CuBTTri, we characterized their ability to deliver NO individually and simultaneously. These MOF composites show great promise to achieve optimal dual NO delivery in real-world medical applications.

Bilayer vascular grafts with on-demand NO and H2S release capabilities

Nitric oxide (NO) and hydrogen sulfide (H2S) gasotransmitters exhibit potential therapeutic effects in the cardiovascular system. Herein, biomimicking multilayer structures of biological blood vessels, bilayer small-diameter vascular grafts (SDVGs) with on-demand NO and H2S release capabilities, were designed and fabricated. The keratin-based H2S donor (KTC) with good biocompatibility and high stability was first synthesized and then electrospun with poly (l-lactide-co-caprolactone) (PLCL) to be used as the outer layer of grafts. The electrospun poly (ε-caprolactone) (PCL) mats were aminolyzed and further chelated with copper (II) ions to construct glutathione peroxidase (GPx)-like structural surfaces for the catalytic generation of NO, which acted as the inner layer of grafts. The on-demand release of NO and H2S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells (HUASMCs). Dual releases of NO and H2S gasotransmitters could enhance their respective production, resulting in enhanced promotion of HUVECs and inhibition of HUASMCs owing to their combined actions. In addition, the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress. In rat abdominal aorta replacement models, the grafts remained patency for 6 months. These grafts were capable of facilitating rapid endothelialization and alleviating neointimal hyperplasia without obvious injury, inflammation, or thrombosis. More importantly, the grafts were expected to avoid calcification with the degradation of the grafts. Taken together, these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.

Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium-Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis.

Long-term blood-contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual-functional surface engineering strategy for CVCs by organic integration of endothelium-mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu2+ -incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu-SB) is designed and robustly fabricated onto commercial CVCs using a facile two-step process. Initially, adhesive ene-functionalized dopamine is covalently reacted with Lys and simultaneously coordinated with bactericidal Cu2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes are grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu-SB coating, endothelium-mimicking function is achieved by combining the catalytic generation of nitric oxide from the chelated Cu2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity show remarkably enhanced long-term anti-thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long-term blood-contacting devices to combat thrombosis and infection.

Recent Advances in Functional Nanomaterials for Catalytic Generation of Nitric Oxide: A Mini Review.

As a gaseous second messenger, nitric oxide (NO) plays an important role in a series of signal pathways. Research on the NO regulation for various disease treatments has aroused wide concern. However, the lack of accurate, controllable, and persistent release of NO has significantly limited the application of NO therapy. Profiting from the booming development of advanced nanotechnology, a mass of nanomaterials with the properties of controllable release have been developed to seek new and effective NO nano-delivery approaches. Nano-delivery systems that generate NO through catalytic reactions exhibit unique superiority in terms of precise and persistent release of NO. Although certain achievements have been made in the catalytically active NO delivery nanomaterials, some basic but critical issues, such as the concept of design, are of low attention. Herein, an overview of the generation of NO through catalytic reactions and the design principles of related nanomaterials are summarized. Then, the nanomaterials that generate NO through catalytic reactions are classified. Finally, the bottlenecks and perspectives are also discussed in depth for the future development of catalytical NO generation nanomaterials.

Silk fibroin/chitosan coating with tunable catalytic nitric oxide generation for surface functionalization of cardiovascular stents

Developing a functional coating for vascular stents with sustainable and tunable NO release remains challenging. In this work, we report a silk fibroin/chitosan-based biopolymer coating incorporating copper ions as a catalyst for NO generation and demonstrate its potential for the surface functionalization of cardiovascular stents. Based on the differences in silk fibroin and chitosan coordinating with copper ions, the loading, bonding, and release of copper ions could be precisely regulated over a wide range by controlling the ratio of silk fibroin and chitosan. This system shows good cytocompatibility for endothelial cells and tunable catalytic activity to decompose S-nitroso-N-acetyl-D-penicillamine (SNAP) for NO generation. Consequently, a functionalized coating with sustainable and tunable NO catalysis generation was developed on the metallic stent. Based on good biocompatibility, tunable NO release, and simple processing, the coating is expected to have great promise in the field of intervention therapy of cardiovascular disease.

A promoting nitric oxide‐releasing coating containing copper ion on ZE21B alloy for potential vascular stent application

Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide (NO) generation containing copper ions (Cu2+) and hyaluronic acid (HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid (HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically, the Cu2+chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N, N′, N″, N″′- tetraacetic acid (DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu2+. The chelated Cu2+enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells (ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells (SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.

Polymeric Amines Induce Nitric Oxide Release from S-Nitrosothiols.

Catalytic generation of nitric oxide (NO) from NO donors by nanomaterials has enabled prolonged NO delivery for various biomedical applications, but this approach requires laborious synthesis routes. In this study, a new class of materials, that is, polymeric amines including polyethyleneimine (PEI), poly-L-lysine, and poly(allylamine hydrochloride), is discovered to induce NO generation from S-nitrosothiols (RSNOs) at physiological conditions. Controlled NO generation can be readily achieved by tuning the concentration of the NO donors (RSNOs) and polymers, and the type and molecular weight of the polymers. Importantly, the mechanism of NO generation by these polymers is deciphered to be attributed to the nucleophilic reaction between primary amines on polymers and the SNO groups of RSNOs. The NO-releasing feature of the polymers can be integrated into a suite of materials, for example, simply by embedding PEI into poly(vinyl alcohol) (PVA) hydrogels. The functionality of the PVA/PEI hydrogels is demonstrated for Pseudomonas aeruginosa biofilm prevention with a ≈4log reduction within 6h. As NO has potential therapeutic implications in various diseases, the identification of polymeric amines to induce NO release will open new opportunities in NO-generating biomaterials for antibacterial, antiviral, anticancer, antithrombotic, and wound healing applications.

Cu(II)-functionalized silk fibroin films for the catalytic generation of nitric oxide.

In situ release of nitric oxide (NO) has been suggested to be a potential functionalization strategy for blood-contacting implants. In this study, the NO generation capability catalyzed by the copper ion-incorporated silk fibroin (SF) films in the presence of S-nitroso-N-acetyl-dl-penicillamine (SNAP) is demonstrated. Cu(II) is effectively bound to the surface of the SF film based on metal-protein coordination. The x-ray photoelectron spectroscopy results indicate that copper ions may exist on the surface of the SF film in the form of Cu(II)/Cu(I) coexistence. The degradation behavior showed that the bound copper ions on the surface of the SF films can maintain a slow release in phosphate-buffered saline (PBS) or collagenase IA solution for 7 days. There was no significant difference in the release of copper ions between PBS degradation and enzyme degradation. The loading of copper ions significantly improved the release of NO from SNAP through catalysis. Based on the biological effects of copper ions and the ability to catalyze the release of NO from S-nitrosothiols, copper ion loading provides an option for the construction of bioactive SF biomaterials.

Facile fabrication of biodegradable endothelium-mimicking coatings on bioabsorbable zinc-alloy stents by one-step electrophoretic deposition.

The zinc-alloy stent is one of the best potential candidates for bioabsorbable metal stents because of its appropriate corrosion rate aligned to the duration of the healing process of the surrounding vessel tissues. However, excessive release of zinc ions, causing cytotoxicity of endothelial cells, and insufficient surface bio-functions of Zn-alloy stents lead to considerable challenge in their application. Herein, one-step electrophoretic deposition was employed to apply a hybrid coating of polycarbonate, tannic acid, and copper ions with tailored functions on Zn-alloy stents to enhance their corrosion resistance and provide an endothelium-mimicking surface. Specifically, the synthesized amino-functionalized aliphatic polycarbonates endowed the hybrid coating with specific surface-erosion properties, resulting in superior corrosion resistance and long-term stability in degradation tests both in vitro and in vivo. The immobilized copper ions enabled the catalytic generation of nitric oxide and promoted the adhesion and proliferation of endothelial cells on zinc alloy. The added tannic acid firmly chelated the copper ions and formed durable phenolic-copper-amine crosslinked networks by electrostatic interaction, resulting in long-term stability of the hybrid coating during the 21 day dynamic immersion test. Tannic acid exerted a synergistic antibacterial effect with copper ions as well as a reduction in the inflammatory response to the zinc substrate. In addition, the hybrid coating improved the in vitro hemocompatibility of zinc alloys. By adjusting the amount of chelated copper in the coating system, the biological function of the corresponding coatings can be controlled, providing a facile surface treatment strategy to promote the progress of zinc-alloy stents in clinical applications.

Facile fabrication of copper-incorporating poly(ε-caprolactone)/keratin mats for tissue-engineered vascular grafts with the potential of catalytic nitric oxide generation.

Tissue-engineered vascular grafts (TEVGs) provide a new alternative for vascular construction. Nitric oxide (NO) is capable of promoting vascular tissue regeneration and reducing restenosis caused by vascular implantation. Therefore, in situ production of NO by catalytic decomposition of the endogenous donor is a promising strategy to fabricate a TEVG. In this study, poly(ε-caprolactone) (PCL) was first electrospun with keratin (Ker) to afford PCL/Ker mats and then incorporated with Cu(II) ions through multiple interactions. This strategy is very simple, green, and facile. Particularly, the incorporated Cu(II) ions were partially reduced to Cu(I) ions due to the reducibility of keratin. The chelated copper ions were expected to catalyze the generation of NO from endogenous S-nitrosothiol (RSNO). As a result, PCL/Ker-Cu mats selectively accelerated the adhesion, migration, and growth of human umbilical vein endothelial cells (HUVECs), while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, these mats exhibited excellent blood compatibility and significant antibacterial activity. Vascular implantation in vivo indicated that the tubular mats could inhibit thrombus formation and retain patency for 3 months after implantation in the rabbit carotid artery. More importantly, vascular remodeling was observed during follow-up, including a complete endothelium and smooth muscle layer. Taken together, the PCL/Ker-Cu mats have great potential application in vascular tissue regeneration.

Modulating nitric oxide-generating activity of zinc oxide by morphology control and surface modification

Zinc oxide (ZnO) has emerged as a promising material for nitric oxide (NO) delivery owing to its intrinsic enzyme-mimicking activities to catalyze NO prodrugs S-nitrosoglutathione (GSNO) and β-gal-NONOate for NO generation. The catalytic performance of enzyme mimics is strongly dependent on their size, shape, and surface chemistry; however, no studies have evaluated the influence of the aforementioned factors on the NO-generating activity of ZnO. Understanding these factors will provide an opportunity to tune NO generation profiles to accommodate diverse biomedical applications. In this paper, for the first time, we demonstrate that the activity of ZnO towards catalytic NO generation is shape-dependent, resulting from the different crystal growth directions of these particles. We modified the surfaces of ZnO particles with zeolitic imidazolate framework (ZIF-8) by in situ synthesis and observed that ZnO/ZIF-8 retained 60% of its NO-generating potency. The newly formed ZnO/ZIF-8 particles were shown to catalytically decompose both endogenous (GSNO) and exogenous (β-gal-NONOate and S-nitroso-N-acetylpenicillamine (SNAP)) prodrugs to generate NO at physiological conditions. In addition, we design the first platform that combines NO-generating and superoxide radical scavenging properties by encapsulating a natural enzyme, superoxidase dismutase (SOD), into ZnO/ZIF-8 particles, which holds great promise towards combinatorial therapy.

Stepwise immobilization of keratin-dopamine conjugates and gold nanoparticles on PET sheets for potential vascular graft with the catalytic generation of nitric oxide

Gold nanoparticles(AuNPs) are capable to catalyze the nitric oxide (NO) generation from endogenous and exogenous donors, thereby promoting re-endothelialization and inhibiting intimal hyperplasia and thrombosis. Herein, keratin-dopamine conjugates were synthesized and then immobilized on the surface of the pre-aminolyzed poly(ethylene terephthalate) (PET) via self-polymerization of dopamine residue, following by the formation of AuNPs in situ without extra reductant. The modified PET sheets(PET-AuNPs) could promote the growth of HUVECs while inhibit the proliferation of HUASMCs due to their catalytic generation of NO from GSNO. In addition, these sheets exhibited antibacterial properties and good blood compatibility without hemolysis. Taken together, this strategy for designing prosthetic vascular grafts to treat cardiovascular diseases has great potential.

The Immunomodulatory Potential of Copper and Silver Based Self-Assembled Metal Organic Biohybrids Nanomaterials in Cancer Theranostics.

Copper high aspect ratio structures (CuHARS) and silver cystine nanoparticles (AgCysNPs) are two unique micro/nano particles under study here that show extensive anti-cancer effects on a glioma tumor cell line. These micro/nano particles have shown potent toxicity in the presence of inflammatory stimulus (combination of tumor necrosis factor, [TNF] and lipo-polysaccharide, LPS). CuHARS with a concentration of 20 μg/ml uniquely increased the catalytic generation of nitric oxide (NO), an important contributor in the immune system. This NO was generated in a cell culture tumor microenvironment (TME) in the presence of 25 µM S-nitrosothiol (cysteine-NO) and the inflammatory stimulus. CuHARS increased the NO production by 68.75% when compared to untreated glioma cells with CysNO and inflammatory stimulus. The production of NO was significantly higher under similar circumstances in the case of normal primary structural cells like brain microvascular endothelial cells (BMVECs). The production of NO by BMVECs went up by 181.25% compared to glioma cells. This significant increase in the NO concentration could have added up to tumorigenesis but the anti-cancer effect of CuHARS was prominent enough to lower down the viability of glioma cells by approximately 20% and increased the metabolism of structural cells, BMVECs by approximately 200%. The immunomodulatory effect of NO in the TME under these circumstances in the presence of the novel micro/nano material, CuHARS has risen up compared to the effect of inflammatory stimulus alone. The potency and specific nature of these materials toward tumor cells may make them suitable candidates for cancer treatment. Successive treatment of CuHARS to glioma cells also proved to be an effective approach considering the decrease in the total count of cells by 11.84 fold in case of three successive treatments compared to a single dose which only decreased the cell count by 2.45 fold showing the dose-dependent increasing toxicity toward glioma cells. AgCysNPs are another potent nanomaterial which also proved its significant toxic nature toward tumor cell lines as demonstrated here, but their immunomodulatory response is still unclear and needs to be explored further.

Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs.

The highly diverse biological roles of nitric oxide (NO) in both physiological and pathophysiological processes have prompted great interest in the use of NO as a therapeutic agent in various biomedical applications. NO can exert either protective or deleterious effects depending on its concentration and the location where it is delivered or generated. This double-edged attribute, together with the short half-life of NO in biological systems, poses a major challenge to the realization of the full therapeutic potential of this molecule. Controlled release strategies show an admirable degree of precision with regard to the spatiotemporal dosing of NO but are disadvantaged by the finite NO deliverable payload. In turn, enzyme-prodrug therapy techniques afford enhanced deliverable payload but are troubled by the inherent low stability of natural enzymes, as well as the requirement to control pharmacokinetics for the exogenous prodrugs. The past decade has seen the advent of a new paradigm in controlled delivery of NO, namely localized bioconversion of the endogenous prodrugs of NO, specifically by enzyme mimics. These early developments are presented, successes of this strategy are highlighted, and possible future work on this avenue of research is critically discussed.

Catalytic Generation of Nitric Oxide from Poly(ε-caprolactone)/Phosphobetainized Keratin Mats for a Vascular Tissue Engineering Scaffold.

Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.

Nanosized copper(ii) oxide/silica for catalytic generation of nitric oxide from S-nitrosothiols.

Nitric oxide NO, mediates inflammatory and thrombotic processes and designing biomaterials capable of releasing NO in contact with biological tissues is considered to be a major factor aimed at improving their bio- and haemocompatibility and antibacterial properties. Their NO-releasing capacity however is limited by the amount of the NO-containing substance incorporated in the bulk or immobilised on the surface of a biomaterial. An alternative approach is based on the design of a material generating nitric oxide from endogenous NO bearing metabolites by their catalytic decomposition. It offers, at least in theory, an unlimited source of NO for as long as the material remains in contact with blood and the catalyst maintains its activity. In this paper we studied the catalytic properties of novel nanostructured CuO/SiO2 catalysts in generating NO by decomposition of S-nitrosoglutathione (GSNO) in vitro. CuO/SiO2 catalysts with different CuO loadings were synthesized by chemisorption of copper(ii) acetylacetonate on fumed nanosilica followed by calcination. CuO content was controlled by a number of chemisorption-calcination cycles. Fourier-transform infrared spectroscopy and thermogravimetric analysis confirmed the formation of CuO/SiO2 nanoparticles (NPs) with particle size of CuO phase in the range from 71 to 88 nm. Scanning electron microscopy images revealed a uniform distribution of NPs without their sintering or agglomeration. All the materials of the CuO/SiO2 NP series exhibited NO-generating activity from GSNO confirmed by the Griess assay and by measuring the concentration of nitrite and nitrate anions in model solutions such as phosphate buffered saline and bovine serum. This activity is dependent on the material specific surface area and CuO exposure on the surface rather than CuO bulk content. The rate of NO production increased at higher initial concentration of the NO-bearing substrate studied in the range between 0.01 mM and 1.0 mM RSNO, which covers its physiological level. CuO/SiO2 NPs can be used to design polymers with NO generating properties at blood-biomaterial interface which are expected to have improved biocompatibility thus enhancing their potential for medical applications such as surgical tubing, peripheral venous catheters, auxiliary blood circulation devices and drug-eluting balloons.

Polycaprolactone/gelatin degradable vascular grafts simulating endothelium functions modified by nitric oxide generation.

Aim: Host remolding with scaffolds degradation and rapid formation of a complete endothelium, are prospective solutions for improving performance of small diameter vascular grafts. Materials & methods: For this purpose, microfibrous polycaprolactone (PCL)/gelatin scaffolds were prepared by electrospinning and subsequently functionalized with heparin and organoselenium-immobilized polyethyleneimine for nitric oxide generation through layer-by-layer self-assembly. Results: Our results showed that modified PCL/gelatin grafts had strong catalytic nitric oxide generation capacity and facilitated the enhanced attachment of endothelial cells, compared with control scaffold groups. Meanwhile, the modified grafts exhibited good hemocombatility, rapid endothelialization and smooth muscle cell regeneration. Conclusion: Modification of biodegradable scaffolds, proposed in this work, could enhance biological functions of vascular grafts and provides new strategies for the construction of small diameter vascular grafts.

PCL/sulfonated keratin mats for vascular tissue engineering scaffold with potential of catalytic nitric oxide generation.

Heparin-like polymers have a good anticoagulant effect due to some groups similar to heparin. Herein, sulfonated keratin(SK) was prepared by chain transfer radical polymerization of 3-sulfopropyl methacrylate(SPMA) to improve blood coagulation nature of keratin. Poly(ε-caprolactone)(PCL)/SK nanofibrous mats with the ratio of 7 and 3 were then fabricated by electrospinning. In vitro cytotoxicity and blood compatibility tests were performed to assess the biocompatibility. Viability of NIH 3T3 cells on PCL/SK mats was higher than that on the pristine PCL mats, indicating their good cytocompatibility. These sulfonated keratin-containing mats enhanced endothelial cell growth, while inhibited smooth muscle cell proliferation and reduced platelet adhesion in the presence of GSH and GSNO, as a result of NO generation. Furthermore, the biocomposite mats prolonged the activated partial thromboplastin time(APTT) effectively without hemolysis. Taken together, PCL/SK mats are potential for applications in vascular tissue engineering.

Development of Cu-Modified PVC and PU for Catalytic Generation of Nitric Oxide

Nitric oxide (NO) generating surfaces are potentially promising for improving haemocompatibility of blood-contacting biomaterials. In the present report, Cu-modified poly(vinyl chloride) (PVC) and polyurethane (PU) were prepared via polydopamine (pDA)-assisted chelation. The copper content on the PVC and PU modified surfaces, assessed by inductively coupled plasma - optical emission spectrometry (ICP-OES), were about 3.86 and 6.04 nmol·cm−2, respectively. The Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) data suggest that copper is attached to the polymer surface through complex formation with pDA. The cumulative leaching of copper from modified PVC and PU during the five day incubation in phosphate buffered saline (PBS), measured by inductively coupled plasma mass spectrometry (ICP-MS), was about 50.7 ppb and 48 ppb, respectively which is within its physiological level. Modified polymers were tested for their ability to catalytically generate NO by decomposing of endogenous S-nitrosothiol (GSNO). The obtained data show that Cu-modified PVC and PU exhibited the capacity to generate physiological levels of NO which could be a foundation for developing new biocompatible materials with NO-based therapeutics.

Electrospun PCL/keratin/AuNPs mats with the catalytic generation of nitric oxide for potential of vascular tissue engineering.

Nitric oxide (NO)-generating materials are beneficial for vascular tissue engineering (VTE) scaffold because the produced NO would enhance endothelial cells viability while inhibit smooth muscle cell (SMC) proliferation and reduce platelet adhesion, resulting in ideal hemocompatibility and endothelialization. Herein, poly(ε-caprolactone) (PCL)/keratin biocomposite mats were first fabricated, followed by in situ gold (Au) nanoparticles loading to afford PCL/keratin/AuNPs mats. These mats were characterized using field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The PCL/keratin/AuNPs mats were demonstrated to be capable of catalyzing NO release in the mimicked blood microenvironments. The generated NO could enhance human umbilical vein endothelial cell growth and inhibit human umbilical arterial SMC viability. In addition, these mats maintained the antibacterial activity of Au nanoparticles with good blood compatibility. Taken together, these keratin-based composite mats have potential usage in the VTE. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3239-3247, 2018.