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Cited by 251Polymer Surface Interaction StudiesNitric Oxide and Endothelin EffectsAntimicrobial agents and applications

Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

Open access
Wo, Yaqi, Brisbois, Elizabeth J., Bartlett, Robert H., Meyerhoff, Mark E.·2016·Biomaterials Science
DOI 10.1039/c6bm00271dPMC PMC4955746
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Abstract

Potential biomedical applications of nitric oxide (NO) releasing polymers.

Verified 2026-10-06 · 6 references not checked yet

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that nitric oxide (NO)-releasing or NO-generating polymers can provide dual antithrombotic and antimicrobial action for blood-contacting biomedical devices. It surveys NO donor chemistry, polymer fabrication strategies, and in vitro/in vivo applications, with emphasis on N-diazeniumdiolates (NONOates) and S-nitrosothiols (RSNOs).

Key findings

  • NO is an endogenous molecule that inhibits platelet activation/adhesion and bacterial proliferation/biofilm formation; polymers that release or generate NO can therefore address both thrombosis and infection, unlike many conventional single-function coatings.
  • NONOates and RSNOs are leading NO donors. NONOates generate two NO per donor via hydrolysis, with half-lives ranging from 1.8 s for PROLI/NO to 20 h for DETA/NO. SNAP-doped E2As retained 82% of initial SNAP after 2 months at 37 °C and released NO for up to 20 d; SNAP in CarboSil was stable for at least 8 months; solvent-impregnated silicone Foley catheters loaded 5.43 ± 0.15 wt% SNAP and released NO for >4 weeks.
  • In rabbit extracorporeal circulation models, DBHD/N2O2 + PLGA tubing preserved platelet count at 79 ± 11% versus 54 ± 6% for controls; SNAP/E2As-coated circuits preserved 100 ± 7% versus 60 ± 6% and reduced thrombus by 33%; Cu0 nanoparticle circuits with SNAP infusion reduced thrombus to 0.4 ± 0.2 versus 3.2 ± 0.2 and 4.9 ± 0.5 pixel/cm2. In sheep jugular implants, 10 wt% SNAP/E2As catheters showed 70% less thrombus and 90% less bacterial adhesion than controls.
  • Antibacterial/antibiofilm results include NO-releasing silicone rubber films reducing S. aureus by 98.4% and E. coli by 99.9%; electrochemical NO catheters lowering live E. coli biofilm by >99.9% after 3 h; and a water-soluble polysaccharide NO donor producing an 8-log reduction in E. coli, A. baumannii, and S. aureus after 24 h. Wound studies reported PEI/NONOate nanoparticles reducing MRSA-infected mouse wound area to 25% at 7 d, GSNO/chitosan dressings nearly healing rat wounds at 15 d, and NO-releasing PU burn dressings giving a 4-log bacterial reduction.

Methods

  • Narrative review of prior literature, not a primary experimental study. It synthesizes work on NO donor chemistry (NONOates, RSNOs, metal nitrosyls, nitrite, etc.), polymer preparation methods (covalent attachment, physical encapsulation, catalytic generation), and biomedical applications.
  • Data/sample: cited in vitro and in vivo studies involving polymers, catheters, grafts, sensors, extracorporeal circuits, wound dressings, and various thrombosis or bacterial models. No new sample or dataset was collected.
  • Main analysis: qualitative synthesis of mechanisms, material designs, NO release metrics, and reported antithrombotic/antimicrobial outcomes; no systematic search strategy, meta-analysis, or formal risk-of-bias assessment is described.

Limitations

  • Stated in the conclusions: remaining challenges include more stable NO donors and polymer scaffolds, controlled spatial and temporal NO delivery, long-term NO release, understanding dose-dependent biological responses, and clinical translation.
  • Evident from the text: as a narrative review, it does not provide a systematic search or quantitative pooling; cited studies vary widely in species, device type, NO flux, duration, and endpoints, limiting direct comparison.
  • Evident: some discussed technologies have specific drawbacks noted in the text, such as copper ion leaching, potential nitrosamine formation, pH-dependent antibacterial surfaces being difficult to apply in buffered blood, and PEG susceptibility to oxidative damage.

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Integrity signals

Registry

Crossref · 10.1039/c6bm00271d

Cites

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Statistics

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    “The incorporation of these blood-contacting materials is usually complicated by foreign body responses that is initiated by the coagulation cascade1”
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    Polymer surfaces with segmented block co-polymers that form phase-separated structures exhibit less bacterial adhesion and cell attachment.

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    PEG's susceptibility to oxidative damage in vivo limits its long-term application in complex media.

    “However, the susceptibility of PEG to oxidative damage, especially in the presence of O2, transition metal ions or certain enzymes in vivo, has limited its long-term application in complex media.59,60”
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    Super-hydrophobic polymer surfaces with water contact angles above 150°, low surface energy, and self-cleaning properties resist microbial cell adhesion in short-term applications.

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    Nitric oxide is an endogenous gas that can suppress platelet activation and also limit bacterial growth and attachment.

    “Nitric oxide is an endogenous gas molecule that can inhibit platelet activation as well as bacterial proliferation and adhesion.”
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    Premisecitation

    Blood contact with foreign materials activates Factor XII and Factor XI, which then adhere to the polymer surface.

    “Exposure of blood to foreign materials will cause plasma proteins, such as Factor XII and Factor XI, to be activated and adhere to the polymer surface.”
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    Surgical procedures using these devices can injure vessel walls, disrupt blood homeostasis, and release tissue factor, causing platelet activation through the extrinsic pathway.

    “Further, surgical procedures that utilize these devices have the potential to injure the vessel wall, disrupt blood homeostasis and release tissue factor, also causing platelet activation and concomitant conformational changes as well (extrinsic pathway).1–6”
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    Hydrogels tend to prevent cell and protein adhesion because of their hydrophilicity and water retention, and are considered biocompatible.

    “Due to their hydrophilicity and excellent water retention properties, they have the natural tendency to prevent cell and protein adhesion and are considered to be very biocompatible and desirable in biomedical applications.”
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    Activated proteins interact with platelet GPIIb/IIIa, which binds fibrinogen, vWF, fibronectin, and vitronectin, leading to platelet activation and aggregation through the intrinsic pathway.

    “The activated protein will interact with platelet surface membrane receptor GPIIb/IIIa, that can bind with fibrinogen, von Willebrand Factors (vWF), fibronectin, and vitronectin, which ultimately leads to platelet conformational changes, subsequent release of intracellular agents, (e.g., Factor V, VIII and Ca2+, etc.), and initiates platelet activation and aggregation (intrinsic pathway).2,3”
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    Poly(NiPAAm) has an LCST around 32 °C in water, swells in heparin solution at low temperature, and collapses to release heparin above the LCST.

    “Poly(NiPAAm) has a lower critical solution temperature (LCST) in aqueous solution, around 32 °C, which enables it to swell when immersed in a heparin solution at low temperature (e.g., room temperature, RT) and uptake this polyanionic drug. When the temperature is higher than LCST, the swollen coating will collapse dramatically and release heparin.”
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    Systemic heparin administration can lead to hemorrhage and thrombocytopenia.

    “However, systemic heparin administration can lead to hemorrhage and thrombocytopenia.”
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    The intrinsic and extrinsic pathways converge to trigger the coagulation cascade, and fibrin traps red blood cells to form a thrombus within hours.

    “Both pathways converge and trigger the coagulation cascade as the activated platelets bind with fibrinogen and other clotting factors. Fibrinogen forms insoluble fibrin, which traps red blood cells and ultimately forms a thrombus within a matter of hours7,8”
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    PEG is non-toxic, water-soluble, and FDA-approved for internal consumption.

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    PEG immobilization is widely used to modify traditional polymer surfaces such as plasticized PVC and PE.

    “For example, immobilization of PEG (-CH2CH2O-) is a widely used method to modify traditional polymer surfaces employed in the medical field, such as plasticized poly(vinyl chloride) (PVC) and polyethylene (PE), etc.46–49”
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    NO-activated sGC reduces intracellular calcium, inhibits platelet PI3-kinase, and reduces affinity and number of fibrinogen binding sites on GPIIb/IIIa.

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    Jennings et al. loaded C2DA into chitosan sponges; release lasted 5 days at 200-1000 μg/mL with a burst on day 1.

    “Jennings et al. attempted to load C2DA into chitosan sponges for localized delivery by initially immersing the sponges into 1 mL of 100 mg/mL C2DA in 10 % enthanol.67 The release of C2DA was determined by HPLC and its release lasted 5 d (200–1000 µg/mL) with a burst of C2DA release on day 1.”
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    In neutral or basic aqueous phase, the morpholinone surface releases dead bacteria and resists bacterial adhesion; under acidic conditions it regenerates bacteria-killing quaternary ammonium groups.

    “In neutral or basic aqueous phase, the surface will release dead bacteria and at the same time resist bacteria adhesion. However, under acidic conditions (e.g., in acetic acid for 20 h), the surface will regenerate bacteria-killing function by reforming the quaternary ammonium functional group.”
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    Premisecitation

    NO has physiological functions including preventing platelet activation and adhesion, inhibiting bacterial proliferation and biofilm formation, enhancing endothelization, immune signaling, and promoting angiogenesis and wound healing.

    “Many researchers have later unveiled NO’s various physiological functions in the human body, including preventing platelet activation and adhesion, inhibiting bacterial proliferation and biofilm formation, enhancing endothelization, signaling in the immune system’s response, and promoting angiogenesis and the wound healing process.112,114–117”
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    Premisecitation

    cGMP increases cAMP indirectly through phosphodiesterase III, decreasing intracellular calcium.

    “In addition, the cGMP increases cyclic adenosine monophosphate (cAMP) levels indirectly through phosphodiesterase III, which will also decrease the intracellular calcium concentration.”
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    NO binds to the heme iron of sGC and increases intracellular cGMP.

    “NO binds to the heme iron moiety of sGC and subsequently increases intracellular concentrations of cyclic guanosine monophosphate (cGMP).121,122”
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    Bacterial interference uses active bacteria to inhibit targeted bacteria by competing for common resources.

    “Lastly, bacterial interference is a different concept that uses active bacteria (either probiotic bacteria54,93,94 or bacteria with less virulence95–97) to inhibit the targeted bacteria by competing for common resources in the same environment.”
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    The cationic surface killed 99.9% of E. coli when exposed to a suspension of 10^10 cells/mL for 1 hour, then hydrolyzed to a nonfouling zwitterionic surface and released 98% of bacterial residue after 8 days at 37 °C and pH 10.0.

    “The cationic surface can kill 99.9% of E. coli bacteria when exposed to a suspension of 1010 cells/mL for 1 h, and then it hydrolyzes into a nonfouling zwitterionic surface and releases 98 % of the bacterial residue after 8 d at 37 °C and pH 10.0.”
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    NO was identified as endothelium-derived relaxation factor in the Nobel Prize-winning discovery by Ignarro, Furchgott, and Murad in 1987.

    “Nitric oxide (NO), a diatomic free radical, was identified as the endothelium-derived relaxation factor (EDRF) in the Nobel Prize-winning discovery by Ignarro, Furchgott, and Murad in 1987.20,108–113”
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    Premisecitation

    The human body synthesizes bio-regulatory NO from L-arginine via three NOS isoforms: eNOS, nNOS, and iNOS.

    “The human body synthesizes a large quantity of bio-regulatory NO from the substrate L-arginine via three distinct isoforms of nitric oxide synthase (NOS), including endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS).118–120”
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    One patient had UTI symptoms caused by Pseudomonas, but none had UTI attributable to E. coli HU2117 colonization.

    “One patient had urinary tract infection (UTI) symptoms caused by Pseudomonas but none of the patients experienced UTI attributable to the colonization of E. coli HU2117.”
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    Premisecitation

    Zwitterionic polymers have equimolar anionic and cationic groups, form a hydration layer via electrostatic interaction, and resist plasma protein and bacterial cell adhesion.

    “Zwitterionic polymers are polymers with equimolar number of homogeneously distributed anionic and cationic groups on their polymer chains, that form a hydration layer on the surface of the material through electrostatic interaction and therefore resists plasma protein and bacterial cell adhesion.64,100,101”
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    Release-based bactericidal surfaces damage bacterial cell membranes and disrupt bacterial enzymes, DNA, proteins, and cell membranes.

    “and 2) release-based bactericidal (e.g., metal ions, antibiotics, etc.), which damage the bacterial cell membrane as well as disrupt the function of bacterial enzymes, DNA, proteins and cell membranes.64”
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    • cites [64] Yu Q Wu Z Chen H Acta Biomater 2015 16 1 13 25637065

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Achieving needed pH changes within blood will be more challenging because blood is relatively strongly buffered.

    “However, achieving the needed changes in pH within blood, which is relatively strongly buffered, will be more challenging.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    The half-lives of synthesized NONOates depend strongly on the amine precursor structure and on hydrogen-bonding stabilization from additional amines in the molecule.

    “The half-lives of the synthesized NONOates strongly depend on the structure of the amine precursors and hydrogen bonding stabilization from additional amines within the molecule.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    N-diazeniumdiolates are formed when primary or secondary amines react with NO under high pressure in the presence of base at low temperatures.

    “N-Diazeniumdiolates (1-amino-substituted diazen-1-ium-1,2-diolate) are a class of NO donor molecules formed by reactions between primary or secondary amines with NO under high pressure (e.g., 5 atm) in the presence of base (either an unreacted amine substrate or an added metal alkoxide base) at low temperatures.1,136”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Naghavi N De Mel A Alavijeh OS Cousins BG Seifalian AM Small 2013 9 22 35 23136136

      Not checked in the free run.

    • cites [136] Hrabie Ja Keefer LK Chem. Rev 2002 102 1135 1154 11942789

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Metal NO complexes include manganese, iron, and ruthenium complexes, with sodium nitroprusside being the most common.

    “Many different metal NO complexes have been reported, including manganese,108,136 iron144 and ruthenium-NO108,111,136 complexes, with sodium nitroprusside (Na2[Fe(CN)5NO], SNP) being the most common.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [108] Seabra AB Durán N J Mater. Chem 2010 20 1624

      Not checked in the free run.

    • cites [136] Hrabie Ja Keefer LK Chem. Rev 2002 102 1135 1154 11942789

      Not checked in the free run.

    • cites [144] Grossi L D’Angelo S J Med. Chem 2005 48 2622 2626 15801852

      Not checked in the free run.

    • cites [111] Nichols SP Storm WL Koh A Schoenfisch MH Adv. Drug Deliv. Rev 2012 64 1177 1188 22433782 PMC3383916

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Nitroglycerin's low bioavailability limits its use as an efficient NO donor and complicates clinical treatment.

    “This low bioavailability limits nitroglycerin’s use as an efficient NO donor and complicates clinical treatments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Tissue- and metabolite-independent NO release from these donors prevents tolerance build-up, making them more suitable for biomedical applications.

    “Furthermore, the tissue and metabolite independent release also avoids the build-up of tolerance over time, which makes these agents more suitable for biomedical applications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Three main strategies for increasing NO bioavailability are exercise/diet, drugs that alter enzymatic NO production, and modified polymeric materials that deliver NO exogenously.

    “There are three main strategies for increasing NO bioavailability: 1) by participating in physical exercise and controlling certain dietary components (e.g., nitrate-rich diet);132,133 2) by administrating drugs that alter the enzymatic production of NO through nitric oxide synthases (NOSs) and increase the biosynthesis of NO endogenously;117 and 3) by using modified polymeric materials that can”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [132] Lundberg JO Gladwin MT Weitzberg E Nat. Rev. Drug Discov 2015 14 623 641 26265312 source

      Not checked in the free run.

    • cites [133] Lundberg JO Weitzberg E Gladwin MT Crit. Care Med 2008 7 156 167 18167491 source

      Not checked in the free run.

    • cites [117] Carpenter AW Schoenfisch MH Chem. Soc. Rev 2012 41 3742 3752 22362384 PMC3341526 source

      Not checked in the free run.

    • cites [3] Brisbois EJ Handa H Meyerhoff ME Puoci F Advanced Polymers in Medicine 2015 Springer International Publishing, Cham 481 511

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [109] Frost MC Reynolds MM Meyerhoff ME Biomaterials 2005 26 1685 1693 15576142 source

      Not checked in the free run.

    • cites [110] Reynolds MM Frost MC Meyerhoff ME Free Radic. Biol. Med 2004 37 926 936 15336308 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RSNOs are an endogenous class of NO donors and natural transporters of NO in tissues and blood.

    “S-Nitrosothiols (RSNO) represent an endogenous class of NO donors and natural transporters of NO within tissues and blood.120,158”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [120] Jen MC Serrano MC van Lith R Ameer GA Adv. Funct. Mater 2012 22 239 260 25067935 PMC4111277 source

      Not checked in the free run.

    • cites [158] Stamler JS Jaraki O Osborne J Simon DI Keaney J Vita J Singel D Valeri CR Loscalzo J Proc. Natl. Acad. Sci. U. S. A 1992 89 7674 7677 1502182 PMC49773 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nitroglycerin, sodium nitroprusside, and molsidomine have been used clinically for chest pain, blood pressure control, and pulmonary hypertension, respectively.

    “Various NO-related drugs have been used in the clinical settings for many years: nitroglycerin (converted to NO by enzymes) for chest pain, sodium nitroprusside for controlling blood pressure, and molsidomine for pulmonary hypertension.131”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [131] Hanson SR Hutsell TC Keefer LK Mooradian DL Smith DJ Adv. Pharmacol 1995 34 383 398 8562447 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Borate additives cannot extend NO release beyond a few days and are cytotoxic to endothelial cells.

    “Unfortunately, the borate additives are not ideal because of their inability to extend the NO release to more than a few days and their cytotoxicity toward endothelial cells.154,155”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [154] Handa H Brisbois EJ Major TC J Mater. Chem. B 2013 1 3578 3587 PMC3728720 23914297

      Not checked in the free run.

    • cites [155] Handa H Major TC Brisbois EJ Amoako KA Meyerhoff ME Bartlett RH J Mater. Chem. B 2014 2 1059 1067 PMC3952273 24634777

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PLGA is biocompatible, biodegradable, has tunable mechanical properties and a wide range of erosion times, and is FDA-approved for controlled delivery devices.

    “PLGA is a biocompatible and biodegradable polymer, with tunable mechanical properties and wide range of erosion times. Further, it is already approved for use by the FDA for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules.157”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [157] Makadia HK Siegel SJ Polymers (Basel) 2011 3 1377 1397 22577513 PMC3347861

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Surgery or trauma that destroys the endothelial lining and certain vascular diseases increase superoxide anions, which react with NO and reduce its bioavailability.

    “Some surgery interventions or trauma that destroys the endothelial lining, as well as certain vascular diseases, will lead to an increased level of superoxide anions and that react with NO and reduce its bioavailablity.119,130”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [119] Vural KM Bayazit M Eur. J. Vasc. Endovasc. Surg 2001 22 285 293 11563885 source

      Not checked in the free run.

    • cites [130] Ignarro L Buga G Proc. Natl. Acad. Sci. U. S. A 1987 84 9265 9269 2827174 PMC299734 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A second route for NO-mediated cytotoxicity involves formation of S-nitrosothiols: NO oxidizes to N2O3, which reacts with cysteine sulfhydryl groups on membrane proteins to form RSNO, altering protein function and causing cell stasis or death.

    “A second possible route reported for NO mediated cytotoxicity relies upon the formation of S-nitrosothiols (RSNO) in which after oxidation of NO to N2O3 the N2O3 can react with sulfhydryl groups on cysteine residues of membrane proteins to create RSNO structures that alter protein functionality, leading to cell stasis or cell death.108”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Seabra AB Durán N J Mater. Chem 2010 20 1624

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Sodium nitroprusside is used as a potent vasodilator in hypertensive emergencies and releases NO in the presence of reducing agents or light.

    “SNP is often used as a potent vasodilator in hypertensive emergencies,144 which releases NO in the presence of reducing agents (e.g., thiol-containing compounds such as cysteine or glutathione) or by illumination with near-infrared or visible light.111,120,144”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [111] Nichols SP Storm WL Koh A Schoenfisch MH Adv. Drug Deliv. Rev 2012 64 1177 1188 22433782 PMC3383916

      Not checked in the free run.

    • cites [120] Jen MC Serrano MC van Lith R Ameer GA Adv. Funct. Mater 2012 22 239 260 25067935 PMC4111277

      Not checked in the free run.

    • cites [144] Grossi L D’Angelo S J Med. Chem 2005 48 2622 2626 15801852

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    N-diazeniumdiolates and S-nitrosothiols are leading candidates for controlled NO delivery because they are relatively stable, release NO spontaneously under physiological conditions without enzymes in a predictable way, and have higher in vivo bioavailability.

    “Many researchers over the past two decades have focused on using N-diazeniumdiolates (NONOates) and S-nitrosothiols (RSNOs) as leading candidates for controlled NO delivery due to their relatively high stability, their ability to spontaneously release NO under physiological conditions (e.g., no enzyme required) in a predictable manner, and their higher bioavailability in vivo.3,120,135”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Brisbois EJ Handa H Meyerhoff ME Puoci F Advanced Polymers in Medicine 2015 Springer International Publishing, Cham 481 511

      Not checked in the free run.

    • cites [120] Jen MC Serrano MC van Lith R Ameer GA Adv. Funct. Mater 2012 22 239 260 25067935 PMC4111277

      Not checked in the free run.

    • cites [135] Riccio Da Schoenfisch MH Chem. Soc. Rev 2012 41 3731 3741 22362355 PMC3341515

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GSNO is present endogenously in blood, making it more biocompatible and attractive for applications such as promoting wound healing in mice or rats.

    “GSNO is present in blood endogenously, which makes it innately more biocompatible and attractive for many applications, such as promoting wound healing process in mice or rats.177–180”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [177] Seabra AB Beck R Guterres S Pohlmann A Nanocosmetics and Nanomedicines 2011 Berlin, Heidelberg Springer Berlin Heidelberg 253 268

      Not checked in the free run.

    • cites [178] Vercelino R Cunha TM Ferreira ES Cunha FQ Ferreira SH De Oliveira MG J Mater. Sci. Mater. Med 2013 24 2157 2169 23756965

      Not checked in the free run.

    • cites [179] Schanuel FS Raggio Santos KS Monte-Alto-Costa A De Oliveira MG Colloids Surfaces B Biointerfaces 2015 130 182 191 25907598

      Not checked in the free run.

    • cites [180] de Oliveira MG Basic Clin. Pharmacol. Toxicol 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    RSNOs can be synthesized by thiol nitrosation in acidic conditions.

    “RSNOs can be synthesized via the thiol nitrosation reaction (such as nitrous acid and alkyl nitrite, etc. in the acidic environment).140”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Wang PG Xian M Tang X Wu X Wen Z Cai T Janczuk AJ Chem. Rev 2002 102 1091 1134 11942788

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    The half-lives of these particles are significantly longer than solution-phase NO donor analogs because many amines at the particle surface increase local pH and reduce NO release rate.

    “The half-lives of the particles are significantly longer than the solution phase NO donor analogs, owing to the fact that a large quantity of amines present at the particle surface can increase the local pH, which then reduces the NO release rate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    This PVC film can concurrently release toxic methanol and formaldehyde as byproducts of the methoxymethyl protecting group, which is undesirable for biomedical materials.

    “In addition, this PVC film can concurrently release toxic methanol and formaldehyde as byproducts of the methoxymethyl-protecting group, which is undesirable for use as materials in biomedical applications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Zhang et al. synthesized NO-releasing fumed silica particles (0.2-0.3 μm) by tethering alkylamines onto the surface using amine-containing silylation reagents with coupling efficiency 50-70%, then converted them to NONOate groups with final NO loading ca. 0.6 μmol/mg.

    “Zhang et al. synthesized NO-releasing fumed silica particles (0.2–0.3 µm) by tethering alkylamines onto the surface of the FS particles using amine-containing silylation reagents (coupling efficiency 50–70 %), and then converted them to corresponding NONOate groups with final NO loading of ca. 0.6 µmol/mg of particle.236”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [236] Zhang H Annich GM Miskulin J Stankiewicz K Osterholzer K Merz SI Bartlett RH Meyerhoff ME J Am. Chem. Soc 2003 125 5015 5024 12708851

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    N-Diazeniumdiolates are the most studied NO donors, and many polymers with secondary amine groups have been chemically modified to create the NONOate moiety.

    “N-Diazeniumdiolates are the most studied NO donors, and many polymers with secondary amine groups have been chemically modified to create the NONOate moiety.109,110,136”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [109] Frost MC Reynolds MM Meyerhoff ME Biomaterials 2005 26 1685 1693 15576142

      Not checked in the free run.

    • cites [110] Reynolds MM Frost MC Meyerhoff ME Free Radic. Biol. Med 2004 37 926 936 15336308

      Not checked in the free run.

    • cites [136] Hrabie Ja Keefer LK Chem. Rev 2002 102 1135 1154 11942789

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SNAP-cyclam can release physiologically relevant NO for up to 3 months in vitro when blended into poly(L-lactic acid) thin films, the longest NO release from SNAP-based polymer films reported to date.

    “Of note, SNAP-cyclam is capable of releasing physiological relevant levels of NO for up to 3 months in vitro when blended into poly(L-lactic acid) thin films, and this represents the longest NO release from SNAP-based polymer films reported to date.243”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [243] McCarthy CW Goldman J Frost MC ACS Appl. Mater. Interfaces 2016 26859235

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Saavedra et al. prepared methoxymethyl-protected diazeniumdiolated piperazine PVC, but NO release was slow because it required hydrolysis of the methoxymethyl protecting group.

    “In subsequent studies, Saavedra et al. prepared methoxymethyl-protected diazeniumdiolated piperazine PVC;237 however, the NO release rate was slow due to the fact that the NO could only be released from the NONOate group after the hydrolysis of the methoxymethyl protecting group.34”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [237] Saavedra JE Booth MN Hrabie JA Davies KM Keefer LK J Org. Chem 1999 64 5124 5131 34237868

      Not checked in the free run.

    • cites [34] Mowery KA Schoenfisch MH Saavedra JE Keefer LK Meyerhoff ME Polymer (Guildf) 2000 21 9 21 10619674

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RSNOs can release NO via thermal or photo-initiated homolytic cleavage of the S-N bond, forming thiyl and NO radicals, with thiyl radical reacting with another RSNO to form disulfide and another NO radical.

    “Thermal or photo-initiated decomposition will lead to homolytic cleavage of the S-N bond, and form thiyl and NO radicals, where thiyl radical (RS•) will react with another RSNO and generate disulfide (RSSR) and another NO radical.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [163] Williams DLH Chem. Commun 1996 1085 1091

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [164] Williams DLH Transit. Met. Chem 1996 21 189 191

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [165] Williams DL Acc. Chem. Res 1999 32 869 876

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [166] Szacilowski K Stasicka Z Prog. React. Kinet. Mech 2001 26 1 58

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [167] Singh RJ Hogg N Joseph J Kalyanaraman B J Biol. Chem 1996 271 18596 18603 8702510 source

      Not checked in the free run.

    • cites [168] Aravindakumar CT Veleeparampil MM Aravind UK Adv. Phys. Chem 2009 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Dendrimers are popular NO delivery vehicles because they can store a large NO reservoir, have tunable sizes, and can be multi-functionalized for targeted delivery.

    “Dendrimers are another class of popular NO delivery vehicles due to their ability to store a large reservoir of NO, have tunable sizes, and to be multi-functionalized for targeted delivery.214,242”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [214] Backlund CJ Worley BV Schoenfisch MH Acta Biomater 2016 29 198 205 26478472 PMC4695967

      Not checked in the free run.

    • cites [242] Stasko NA Schoenfisch MH J Am. Chem. Soc 2006 128 8265 8271 16787091

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The ultimate hydrolysis product of SNAP precursor NAP, penicillamine, is an FDA-approved chelator for heavy metal poisoning such as Wilson's disease.

    “The precursor for SNAP synthesis is N-acetylpenicillamine (NAP), whose ultimate hydrolysis product, penicillamine, is already a FDA approved chelator for treating heavy metal poisoning, such as Wilson’s disease.181–184”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [181] Borthwick TR Benson GD Schugar HJ J Lab. Clin. Med 1980 95 575 580 7359013

      Not checked in the free run.

    • cites [182] Parameshvara V Br. J. Ind. Med 1967 24 73 76 6017143 PMC1008512

      Not checked in the free run.

    • cites [183] Graeme KA Pollack CV J Emerg. Med 1998 16 45 56 9472760

      Not checked in the free run.

    • cites [184] Jones MM Weaver AD Weller WL Res. Commun. Chem. Pathol. Pharmacol 1978 22 581 588 216066

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SNAP has been covalently attached to PDMS, gelatin, and a macrocycle such as cyclam.

    “SNAP has also been covalently attached to PDMS,226 gelatin222 and a macrocycle (e.g., cyclam).243”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [226] Gierke GE Nielsen M Frost MC Sci. Technol. Adv. Mater 2011 12 055007 PMC5074439 27877445

      Not checked in the free run.

    • cites [222] Vogt C Xing Q He W Li B Frost MC Zhao F Biomacromolecules 2013 14 2521 2530 23844781

      Not checked in the free run.

    • cites [243] McCarthy CW Goldman J Frost MC ACS Appl. Mater. Interfaces 2016 26859235

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Such films release NO at levels proportional to visible light intensity, providing the first hydrophobic materials with an external on/off trigger that controls NO release via photodecomposition.

    “However, such films are able to release NO at levels proportional to the intensity of visible light that is allowed to shine on the polymer, providing the first hydrophobic materials that have an external on/off trigger that precisely controls the rate of NO release via a photodecomposition reaction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Keefer and coworkers attached a diazeniumdiolate species to the backbone of PEI to form PEI/NONOate, later used as a flexible NO release coating for PTFE vascular grafts.

    “Keefer and coworkers were one of the earliest groups to covalently attach a diazeniumdiolate species to the backbone of poly(ethylenimine) (PEI) to form PEI/NONOate, which later was used to provide a flexible NO release coating for PTFE vascular grafts.239”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [239] Smith DJ Chakravarthy D Pulfer S Simmons ML Hrabie JA Citro ML Saavedra JE Davies KM Hutsell TC Mooradian DL Hanson SR Keefer LK J Med. Chem 1996 39 1148 1156 8676352

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SNAP is reportedly one of the most stable NO donors due to intermolecular hydrogen bonding and is a promising candidate for long-term NO-releasing polymeric materials.

    “SNAP is reportedly one of the most stable NO donors available, due to its intermolecular hydrogen bonding,162,185 and has already been shown to be a very promising candidate for fabricating long-term NO releasing polymeric materials.161,162,186”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [162] Wo Y Li Z Brisbois EJ Colletta A Wu J Major TC Xi C Bartlett RH Matzger AJ Meyerhoff ME ACS Appl. Mater. Interfaces 2015 7 22218 22227 26393943 PMC4613868

      Not checked in the free run.

    • cites [185] Arulsamy N Bohle DS Butt JA Irvine GJ Jordan PA Sagan E J Am. Chem. Soc 1999 121 7115 7123

      Not checked in the free run.

    • cites [161] Brisbois EJ Handa H Major TC Bartlett RH Meyerhoff ME Biomaterials 2013 34 6957 6966 23777908 PMC3729938

      Not checked in the free run.

    • cites [186] Brisbois EJ Davis RP Jones AM Major TC Bartlett RH Meyerhoff ME Handa H J Mater. Chem. B 2015 3 1639 1645 PMC4326019 25685358

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Wheatley et al. used cobalt-exchanged zeolite-A to absorb and store NO (1.2-1.3 μmol NO/mg zeolite), with release triggered by water at physiological temperature and pH.

    “Wheatley et al. have used cobalt-exchanged zeolite-A to absorb and store NO (1.2–1.3 µmol NO/mg zeolite). The NO release was triggered by contacting with water at physiological temperature and pH, replacing the gaseous NO with cobalt-water interactions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Encapsulating N-diazeniumdiolates within pH- or thermo-sensitive liposomes achieves controlled release; pH or temperature fluctuations change proton influx through the biolayer membrane and induce significant NO release.

    “Other researchers have conducted further studies to encapsulate NO donors within pH126 or thermo-sensitive247 liposomes to achieve controlled release. In short, when N-diazeniumdiolates are encapsulated within liposomes, pH or temperature fluctuations change the proton influx through the biolayer membrane and subsequently induce a significant NO release.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [126] Suchyta DJ Handa H Meyerhoff ME Mol. Pharm 2014 11 645 650 24423090 PMC3993940 source

      Not checked in the free run.

    • cites [247] Tai LA Wang YC Yang CS Nitric Oxide - Biol. Chem 2010 23 60 64 20399280 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mowery et al. prepared diazeniumdiolated DMHD or linear PEI dispersed into plasticized PVC or PU; NO donor leaching was observed by HPLC, raising toxicity concerns if nitrosamine formation occurs and nitrosamines leach into surrounding aqueous environment.

    “Mowery et al.34 prepared diazeniumdiolated N,N-dimethyl-1,6-hexanediamine (DMHD) or linear PEI and dispersed them into plasticized PVC or PU. Unfortunately, NO donor leaching was observed by HPLC and this raises potential concerns regarding toxicity if nitrosamine formation occurs, and such nitrosamines are also leached into the surrounding aqueous environment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Mowery KA Schoenfisch MH Saavedra JE Keefer LK Meyerhoff ME Polymer (Guildf) 2000 21 9 21 10619674

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The average size of NO/PPNPs was 162 ± 19 nm by SEM, with NO release capacity 1.4 μmol NO/mg polymer.

    “The average size of the NO/PPNPs was 162 ± 19 nm as confirmed by scanning electron microscopy (SEM), with a NO release capacity of 1.4 µmol NO/mg polymer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    NO-zeolite samples blended with powdered PTFE or PDMS to increase mechanical stability and pressed as disks for in vitro testing.

    “These NO-zeolite samples were also blended with powdered PTFE or PDMS to increase their mechanical stability and then pressed as disks for in vitro testing.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Dextran-based materials are susceptible to enzymatic degradation by dextranase, and degradation of dextran derivatives is slower and partial compared to unmodified dextran because of chemical modification of the dextran backbone.

    “It has been further demonstrated that these dextran-based materials are susceptible to enzymatic degradation by dextranase, and the degradation of dextran derivatives is slower and partial when compared to the unmodified dextran because of the chemical modification of the dextran backbone.244”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [244] Damodaran VB Place LW Kipper MJ Reynolds MM J Mater. Chem 2012 22 23038

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brisbois et al. discovered SNAP is exceptionally stable when doped within low water uptake biomedical grade polymers such as Elast-eon E2As and CarboSil, releasing NO for up to 3 weeks at physiological conditions.

    “Recently, Brisbois et al. discovered that SNAP is exceptionally stable when doped within several low water uptake biomedical grade polymers, such as Elast-eon E2As and CarboSil, and can release NO for up to 3 weeks at physiological conditions.155,161”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Handa H Major TC Brisbois EJ Amoako KA Meyerhoff ME Bartlett RH J Mater. Chem. B 2014 2 1059 1067 PMC3952273 24634777

      Not checked in the free run.

    • cites [161] Brisbois EJ Handa H Major TC Bartlett RH Meyerhoff ME Biomaterials 2013 34 6957 6966 23777908 PMC3729938

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Kinetic studies showed SNAC releases NO thermally 3.6 times faster than GSNO (11 ± 0.4 min−1 vs 3.1 ± 0.8 min−1); approximately 50% of both NO donors decomposed after only 3 h.

    “Kinetic studies showed that SNAC releases NO thermally 3.6 times faster than GSNO (11 ± 0.4 min−1 vs. 3.1 ± 0.8 min−1); however, approximately 50% of both NO donors had decomposed after only 3 h.231”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [231] Seabra AB Fitzpatrick A Paul J De Oliveira MG Weller R Br. J. Dermatol 2004 151 977 983 15541075

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Riccio et al. designed thiol-modified xerogels from MPTMS and MTMS; thiol nitrosation generated NO loadings up to 1.31 ± 0.07 μmol NO/mg, and films released NO for up to 2 weeks under physiological conditions.

    “Riccio et al. designed thiol-modified xerogels derived from 3-mercaptopropyltrimethoxysilane (MPTMS) and methyltrimethoxysilane (MTMS).216 The subsequent thiol nitrosation generates xerogels with NO loadings up to 1.31 ± 0.07 µmol NO/mg, and films of these materials are capable of releasing NO for up to 2 weeks under physiological conditions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [216] Riccio Da Dobmeier KP Hetrick EM Privett BJ Paul HS Schoenfisch MH Biomaterials 2009 30 4494 4502 19501904 PMC2743564

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  • May combine two claims.

    Premisecitation

    The crystal-polymer composite is stable during storage for at least 8 months because CarboSil hydrophobicity limits water diffusion mainly to the polymer surface and crystalline SNAP is stabilized by intermolecular hydrogen bonds.

    “Additionally, this crystal-polymer composite is very stable during storage for at least 8 months, not only because of the hydrophobicity of the CarboSil polymer that limits water diffusion primarily to only the polymer surface, but also because the crystalline SNAP is stabilized by intermolecular hydrogen bonds.162,252”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [162] Wo Y Li Z Brisbois EJ Colletta A Wu J Major TC Xi C Bartlett RH Matzger AJ Meyerhoff ME ACS Appl. Mater. Interfaces 2015 7 22218 22227 26393943 PMC4613868

      Not checked in the free run.

    • cites [252] de Oliveira MG Shishido SM Seabra AB Morgon NH J Phys. Chem. A 2002 106 8963 8970

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  • May combine two claims.

    Premisereasoning

    Physical encapsulation embeds the NO donor within a polymer matrix without chemical bonding and is less complicated than covalent attachment.

    “Physical encapsulation methods for preparing NO releasing polymers are based on embedding the NO donor within a polymer matrix physically without chemical bonding. This provides a much less complicated method to prepare NO release polymers than covalent attaching NO donors to particle fillers or the polymer backbones.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Incorporating PEI/NONOate into a hydrophobic PLGA nanoparticle matrix restricts spontaneous degradation of the NONOate group and extends NO release lifetime from 12 h to over 6 d.

    “The incorporation of PEI/NONOate into hydrophobic PLGA nanoparticle matrix successfully restricts the spontaneous degradation of the NONOate group and extends the NO release lifetime from 12 h to over 6 d.219”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [219] Yoo J-W Nurhasni H Cao J Choi M Kim I Luel Lee B Jung Y Int. J. Nanomedicine 2015 10 3065 3080 25960648 PMC4411019

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Seabra et al. incorporated GSNO and SNAC into Synperonic F-127 gel using a cold method and formed a hydrogel containing 0.3 mol GSNO or 0.6 mol SNAC per gram of hydrogel.

    “Seabra et al. incorporated GSNO and SNAC into Synperonic F-127 gel using a ‘cold method’251 and formed a hydrogel that contained 0.3 mol of GSNO or 0.6 mol of SNAC per gram of hydrogel.251”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [251] Shishido SM Seabra AB Loh W de Oliveira MG Biomaterials 2003 24 3543 3553 12809783

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Gas storage in porous materials such as zeolites is an attractive method for medicinal applications.

    “Gas storage in porous materials, such as zeolites, is also another attractive method for medicinal applications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lautner et al. encapsulated SNAP into PLGA microspheres using S/O/W and achieved up to 4 weeks of controlled SNAP release from PLGA RG 504, generating localized NO with copper(II) and ascorbate.

    “More recently, Lautner et al. demonstrated the encapsulation of SNAP into PLGA (RG 503H and RG 504) microspheres (20–125 µm in diameter) using a solid-oil-in water (S/O/W) method250 and achieved up to 4 weeks of controlled release of SNAP from PLGA RG 504, which then generates localized NO in the presence of copper (II) and ascorbate.206”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [250] Wischke C Schwendeman SP Int. J. Pharm 2008 364 298 327 18621492

      Not checked in the free run.

    • cites [206] Lautner G Meyerhoff ME Schwendeman SP J Control. Release 2016 225 133 139 26763376 PMC4769910

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  • May combine two claims.

    Premisecitation

    Stasko et al. functionalized generation 4 PAMAM dendrimers with N-acetylpenicillamine or N-acetylcysteine; both scaffolds had NO storage ca. 2 μmol NO/mg polymer after nitrosation.

    “Stasko et al. functionalized generation 4 polyamidoamine (PAMAM) dendrimers with N-acetylpenicillamine or N-acetylcysteine and both macromolecular scaffolds have an NO storage of ca. 2 µmol NO/mg polymer after the required nitrosation raction.213”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [213] Stasko NA Fischer TH Schoenfisch MH Biomacromolecules 2008 9 834 841 18247567 PMC3564213

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  • May combine two claims.

    Premisecitation

    Kim et al. developed NO-releasing films by dispersing GSNO into chitosan; 75% GSNO remained after storing at room temperature for 4 weeks, and a 20 wt% GSNO/chitosan film released NO over 48 h in PBS at 37 °C.

    “Kim et al. developed NO-releasing films by dispersing GSNO into biopolymer chitosan, where 75% GSNO remains after storing at room temperature for 4 weeks. The 20 wt% GSNO/chitosan film released NO over 48 h in PBS buffer at 37 °C.221”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [221] Kim JO Noh JK Thapa RK Hasan N Choi M Kim JH Lee JH Ku SK Yoo JW Int. J. Biol. Macromol 2015 79 217 225 25957720

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  • May combine two claims.

    Premisecitation

    Wo et al. demonstrated that SNAP in CarboSil mainly exists in crystalline form when its concentration exceeds solubility in the polymer, and slow crystal dissolution leads to long-term NO release under physiological conditions.

    “Wo et al. later demonstrated that the SNAP in CarboSil mainly exists in crystalline form when the SNAP concentration exceeds its solubility in the polymer. Ultimately, a slow crystal dissolution process leads to its long-term NO release under physiological conditions.162”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [162] Wo Y Li Z Brisbois EJ Colletta A Wu J Major TC Xi C Bartlett RH Matzger AJ Meyerhoff ME ACS Appl. Mater. Interfaces 2015 7 22218 22227 26393943 PMC4613868

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  • May combine two claims.

    Premisecitation

    Bachelor et al. synthesized more lipophilic dialkylhexamethylenediamine-based NONOates with different alkyl groups to enhance retention of potential byproducts within hydrophobic PVC films and reduce toxicity threat.

    “Bachelor et al.153 synthesized more lipophilic dialkylhexamethylenediamine-based NONOates with different alkyl groups (from methyl to didodecyl) which can enhance the retention of potential byproducts within the hydrophobic PVC films and thereby reduce their toxicity threat to biological systems.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [153] Batchelor MM Reoma SL Fleser PS Nuthakki VK Callahan RE Shanley CJ Politis JK Elmore J Merz SI Meyerhoff ME J Med. Chem 2003 46 5153 5161 14613318

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mcpherson and coworkers prepared liposomes encapsulated with NO and argon gas (NO/Ar-ELIP) by a pressure-freeze and thawing method and used them to attenuate intimal hyperplasia and reduce arterial wall thickness.

    “Mcpherson and coworkers prepared liposomes encapsulated with NO and argon gas (NO/Ar-ELIP) by a pressured-freeze and thawing method. They used these capsules for attenuating intimal hyperplasia and reducing arterial wall thickness.198”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Huang S-L Kee PH Kim H Moody MR Chrzanowski SM Macdonald RC McPherson DD J Am. Coll. Cardiol 2009 54 652 659 19660697 PMC3108325

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  • May combine two claims.

    Premisecitation

    The microbubbles were loaded with NO by exposure to gas-phase NO at 1.5 bar for 2 h; encapsulation was about 1% of NO in the reaction vessel, with final content 3.6 μmol/mg microbubbles.

    “The microbubbles were loaded with NO by exposing to gas phase NO at 1.5 bar for 2 h. The NO encapsulation is about 1% of the NO present in the reaction vessel during the loading procedure, with the final content being 3.6 µmol/mg microbubbles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many polymer modification studies using RSNOs have used PDMS, PVA hydrogel, polyester, and poly(methylmethacrylate) as base polymers.

    “Similar to N-diazeniumdiolates, many other polymer modification studies have been conducted using S-nitrosothiols (RSNOs) as well, including those utilizing PDMS,226 PVA hydrogel,179 polyester and poly(methylmethacrylate),224 as the base polymer materials.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [226] Gierke GE Nielsen M Frost MC Sci. Technol. Adv. Mater 2011 12 055007 PMC5074439 27877445

      Not checked in the free run.

    • cites [179] Schanuel FS Raggio Santos KS Monte-Alto-Costa A De Oliveira MG Colloids Surfaces B Biointerfaces 2015 130 182 191 25907598

      Not checked in the free run.

    • cites [224] Seabra AB Da Silva R De Souza GFP De Oliveira MG Artif. Organs 2008 32 262 267 18370938

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premiseown data

    In a canine model, the NO-releasing O2 sensor more closely represented the real arterial blood gas value than the control sensor, which had a significant discrepancy starting from the first few hours after implantation.

    “The electrochemical response of the NO-releasing O2 sensor more closely represented the real arterial blood gas value measured by a benchtop blood-gas analyzer than the control sensor, which had a significant”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    It remains a challenge to achieve long-term NO release under physiologically relevant conditions, stable storage at room temperature, and high NO donor loading.

    “However, it still remains a challenge to achieve long-term NO release at physiologically relevant conditions, stable storage capability at room temperatures and high NO donor loading.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Both types of NO release tubing exhibited less overall platelet adhesion and thrombus surface coverage compared with controls.

    “Both types of NO release tubing exhibited less overall platelet adhesion and thrombus surface coverage compared to the controls.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [236] Zhang H Annich GM Miskulin J Stankiewicz K Osterholzer K Merz SI Bartlett RH Meyerhoff ME J Am. Chem. Soc 2003 125 5015 5024 12708851

      Not checked in the free run.

    • cites [238] Zhang H Annich GM Miskulin J Osterholzer K Merz SI Bartlett RH Meyerhoff ME Biomaterials 2002 23 1485 1494 11829445

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  • May combine two claims.

    Premisecitation

    50% of copper(II) ion leached out after soaking in GSNO/GSH-containing PBS at room temperature for 7 days, which may limit long-term applications and generate cytotoxicity concerns.

    “However, it was reported that 50 % of copper(II) ion leached out after soaking in GSNO/GSH containing PBS buffer at RT for 7 d, which may limit the use of such polymers for long-term applications and generate cytotoxicity concerns.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Electrochemically generated NO can be modulated by changing applied potentials and achieves between 0.5 and 3.5 × 10−10 mol cm−2 min−1, in the range of physiological NO levels released by endothelial cells.

    “The electrochemically generated NO can be modulated by changing the potentials applied to the electrodes and can achieve between 0.5 and 3.5 × 10−10 mol cm−2 min−1, which is in the range of physiological relevant levels of NO released by the endothelial cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fewer platelets adhered on polymer surfaces with higher NO flux levels; NO reduced platelet adhesion from 14.0 ± 2.1 × 105 cells/cm2 on controls to 2.96 ± 0.18 × 105 cells/cm2 on surfaces with highest NO release of 7.05 × 10−10 mol cm−2 min−1.

    “Fewer platelets adhered on the polymer surfaces with higher NO flux levels, and NO successfully reduced the amount of platelets adhered on the polymer surfaces from 14.0 ± 2.1 × 105 cells/cm2 on the controls to 2.96 ± 0.18 × 105 cells/cm2 on the surfaces with highest NO release of 7.05 × 10−10 mol cm−2 min−1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Zhang et al. prepared PVC tubing with a PU coating containing 20 wt% diazeniumdiolated FS particle fillers and SR tubing with covalently attached DACA/N2O2 as NO releasing polymer tubing circuits for 4 h ECC experiments in rabbits.

    “Zhang et al. prepared PVC tubing with PU coating containing 20 wt% diazeniumdiolated FS particle fillers236 and SR tubing with covalently attached to DACA/N2O2238 as NO releasing polymer tubing circuits for 4 h ECC experiments in a rabbit model.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [236] Zhang H Annich GM Miskulin J Stankiewicz K Osterholzer K Merz SI Bartlett RH Meyerhoff ME J Am. Chem. Soc 2003 125 5015 5024 12708851

      Not checked in the free run.

    • cites [238] Zhang H Annich GM Miskulin J Osterholzer K Merz SI Bartlett RH Meyerhoff ME Biomaterials 2002 23 1485 1494 11829445

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Platelet adhesion and thrombus on sensor surfaces can isolate the sensing area, cause false analytical results, and increase emboli or stroke risk.

    “However, adhesion of platelets, and eventual thrombus formation on the surface of the sensors can occur within a few hours after blood contact, and such processes can not only isolate the chemical sensing area from the bulk of the blood and lead to false analytical results but also increase the risk of emboli or stroke.8,265”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Wu Y Meyerhoff ME Talanta 2008 75 642 650 18585126 PMC2442581 source

      Not checked in the free run.

    • cites [265] Burns KEA McLaren A Can. Respir. J 2009 16 163 165 19851535 PMC2779172 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Tissue factor release and protein absorption trigger the coagulation cascade, and lack of NO production leads to platelet activation, aggregation, and ultimately thrombus formation.

    “The tissue factor release and protein absorption trigger the coagulation cascade and the lack of NO production leads to platelet activation, aggregation, and ultimately thrombus formation.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Diazeniumdiolated cross-linked PEI coated PTFE vascular grafts released NO and were substantially less thrombogenic than controls in a baboon arteriovenous shunt model.

    “The NO-releasing grafts were found to be substantially less thrombogenic than the controls, suggesting considerable promise for this approach to improve the performance of vascular graft after implantation.239”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [239] Smith DJ Chakravarthy D Pulfer S Simmons ML Hrabie JA Citro ML Saavedra JE Davies KM Hutsell TC Mooradian DL Hanson SR Keefer LK J Med. Chem 1996 39 1148 1156 8676352

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Meyerhoff and coworkers demonstrated electrochemical NO generation through a Cu+ ion mediated reduction of inorganic nitrite; Cu+ is generated from oxidation of a copper wire or reduction of Cu(II)TPMA complex.

    “As previously mentioned, Meyerhoff and coworkers have also demonstrated an electrochemical NO generation through a Cu+ ion mediated reduction reaction of inorganic nitrite. The Cu+ ion is generated from oxidation of a copper wire145,146 or the reduction of copper(II)-tri(2-pyridylmethyl)amine (Cu(II)TPMA) complex.147”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [145] Höfler L Koley D Wu J Xi C Meyerhoff ME RSC Adv 2012 2 6765 6767 22888401 PMC3414219

      Not checked in the free run.

    • cites [146] Ren H Colletta A Koley D Wu J Xi C Major TC Bartlett RH Meyerhoff ME Bioelectrochemistry 2015 104 10 16 25588885 PMC4480771

      Not checked in the free run.

    • cites [147] Ren H Wu J Xi C Lehnert N Major T Bartlett RH Meyerhoff ME ACS Appl. Mater. Interfaces 2014 6 3779 3783 24611831 PMC3969097

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    LDH assay was used to determine the amount of platelets adhered onto the polymer surface; LDH is released when platelets are lysed by surfactant and is useful for indicating the amount of adhered cells.

    “A lactate dehydrogenase (LDH) assay was used to determine the amount of platelets adhered onto the polymer surface. LDH, which is normally stored within intact platelet, is released into the bulk solution when the platelets are lysed by surfactant and is a very useful for indication of the amount of cells adhered.259”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [259] Wu Y Zhou Z Meyerhoff ME J Biomed. Mater. Res. A 2007 81 956 963 17252544

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  • May combine two claims.

    Premisecitation

    NO releasing or generating grafts encourage endothelialization or endothelial cell proliferation.

    “The West115 and Wang114 groups both reported that NO releasing/generating grafts encourage endothelialization/endothelial cell proliferation, which can alleviate the complications of thrombosis and intimal hyperplasia (IH) that cause the failure of small diameter vascular grafts without the use of systemic anticoagulants.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [115] Taite LJ Yang P Jun H-W West JL J Biomed. Mater. Res. Part B Appl. Biomater 2007 84B 108 116 17497680

      Not checked in the free run.

    • cites [114] Wang Y Chen S Pan Y Gao J Tang D Kong D Wang S J Mater. Chem. B 2015 3 9212 9222 32263136

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  • May combine two claims.

    Premisecitation

    Schoenfisch et al. coated SR catheters with MAHMA/N2O2 and the NO release lasted more than 20 h in PBS at 37 °C.

    “For example, Schoenfisch et al. coated outer surfaces of SR catheters with 2 wt% (Z)-1-[N-methyl-N-[6–(N-methylammoniohexyl)amino]] diazeniumdiolate (MAHMA/N2O2) and demonstrated that the NO release from the catheter lasted more than 20 h in PBS at 37 °C.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Yoo and coworkers' PEI/NONOate NPs capable of prolonged NO release treated MRSA-infected excisional wounds in mice; wound area was reduced to 25% at the end of 7 d, while untreated wounds showed a thicker scab with no reduction.

    “The photographs of the wounds taken at day 0, 1, 4 and 7 clearly showed an accelerated wound healing process for mice treated with NPs, with wound area reduced to 25% at the end of 7 d. The untreated wounds showed a thicker scab with no reduction in the wound area.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [219] Yoo J-W Nurhasni H Cao J Choi M Kim I Luel Lee B Jung Y Int. J. Nanomedicine 2015 10 3065 3080 25960648 PMC4411019

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    iNOS knockout mice showed diminished collagen deposition, with restoration of normal collagen deposits upon exposure to SNAP, indicating a relationship between NO production and wound healing.

    “Studies using induced NOS (iNOS) knock out mice showed diminished collagen deposition, with the restoration of normal collagen deposits upon exposure to SNAP, indicating the important relationship between NO production and wound healing.293”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [293] Shi HP Efron DT Most D Barbul A Surgery 2001 130 225 229 11490353

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NO releasing polymers have provided a potential strategy for active wound healing dressings, capable of reducing bacterial infections at wound sites and accelerating wound healing for incisional and excisional wounds, burn wounds, and diabetic wounds.

    “Nitric oxide releasing polymers have also provided a potential strategy for use as active wound healing dressings, capable of reducing bacterial infections at wound sites and accelerating the wound healing process for incisional and excisional wounds,179,219,221 burn wounds,290 and diabetic wounds.232”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [179] Schanuel FS Raggio Santos KS Monte-Alto-Costa A De Oliveira MG Colloids Surfaces B Biointerfaces 2015 130 182 191 25907598

      Not checked in the free run.

    • cites [219] Yoo J-W Nurhasni H Cao J Choi M Kim I Luel Lee B Jung Y Int. J. Nanomedicine 2015 10 3065 3080 25960648 PMC4411019

      Not checked in the free run.

    • cites [221] Kim JO Noh JK Thapa RK Hasan N Choi M Kim JH Lee JH Ku SK Yoo JW Int. J. Biol. Macromol 2015 79 217 225 25957720

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Normal fibroblasts do not synthesize NO, but fibroblasts isolated from a regular wound can release NO.

    “While normal fibroblasts do not synthesize NO, it has been demonstrated that fibroblasts isolated from the regular wound can release NO.291”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [291] Schäffer MR Efron PA Thornton FJ Klingel K Gross SS Barbul A J Immunol 1997 158 2375 2381 9036987

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rabbit ECC experiments, PVC circuits coated with SNAP/E2As preserved platelet count during 4 h (100 ± 7% versus 60 ± 6% for controls), with 33% less thrombus formation.

    “Such coated tubing successfully preserved the platelet count during the 4 h of experiments (at 100 ± 7% % vs. 60 ± 6 % for controls), with 33 % less thrombus formation on the tubings’ inner surfaces.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Brisbois EJ Handa H Major TC Bartlett RH Meyerhoff ME Biomaterials 2013 34 6957 6966 23777908 PMC3729938

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    A water-soluble NO releasing chitosan oligosaccharide (0.17-0.46 μmol NO/mL) elicited a 5-log unit reduction in viable bacterial counts with an MBC as low as 400 μg/mL against P. aeruginosa biofilms.

    “The presence of the NO release elicited a 5-log unit reduction in viable bacterial counts with a minimal bactericidal concentration (MBC) of the dendrimer preparation as low as 400 µg/mL.220”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [220] Lu Y Slomberg DL Schoenfisch MH Biomaterials 2014 35 1716 1724 24268196 PMC3889664

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NO released through iNOS enhances angiogenesis, regulates collagen formation, cell proliferation, and wound contractions.

    “The NO released through iNOS enhances angiogenesis, regulates collagen formation, cell proliferation and wound contractions.111,292”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [111] Nichols SP Storm WL Koh A Schoenfisch MH Adv. Drug Deliv. Rev 2012 64 1177 1188 22433782 PMC3383916

      Not checked in the free run.

    • cites [292] Witte MB Barbul A Am. J. Surg 2002 183 406 412 11975928

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NO releasing sol-gel coatings and xerogel films are capable of releasing NO for 5 and 14 d, respectively.

    “Schoenfisch and coworkers have evaluated the antibacterial characteristics of NO releasing sol-gel coatings289 and xerogel films216 which are capable of releasing NO for 5 and 14 d, respectively, against a 108 colony forming units (CFU)/mL saline suspension of P. aeruginosa for up to 4 h.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [289] Nablo BJ Schoenfisch MH J Biomed. Mater. Res. A 2003 67 1276 1283 14624514

      Not checked in the free run.

    • cites [216] Riccio Da Dobmeier KP Hetrick EM Privett BJ Paul HS Schoenfisch MH Biomaterials 2009 30 4494 4502 19501904 PMC2743564

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Backlund et al. synthesized diazeniumdiolated PAMAM dendrimers with different alkyl chain modifications and examined their antibacterial properties against 24 h old S. mutans biofilm at pH 7.4 and 6.4.

    “In a separate study, Backlund et al.214 synthesized diazeniumdiolated PAMAM dendrimers with different alkyl chain modifications and examined their antibacterial properties against 24 h old Streptococcus mutans biofilm (S. mutans) at pH 7.4 and 6.4.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [214] Backlund CJ Worley BV Schoenfisch MH Acta Biomater 2016 29 198 205 26478472 PMC4695967

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The bactericidal action of the NO releasing dendrimers increased with alkyl chain length and lower pH.

    “The bactericidal action of the NO releasing dendrimers was reported to increase with alkyl chain length of the dendrimer and lower pH.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [214] Backlund CJ Worley BV Schoenfisch MH Acta Biomater 2016 29 198 205 26478472 PMC4695967

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A short period of NO release (3 h) was effective at dispersing and killing E. coli biofilm and lowered live bacteria on catheter surfaces by >99.9%.

    “The short period of NO release was effective at dispersing and killing the E. coli biofilm, and could lower the number of live bacteria adhered on the catheter surfaces by > 99.9%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [146] Ren H Colletta A Koley D Wu J Xi C Major TC Bartlett RH Meyerhoff ME Bioelectrochemistry 2015 104 10 16 25588885 PMC4480771

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SNAP-doped E2As catheters implanted in sheep jugular veins for 7 d exhibited 70% less thrombus formation and 90% reduction of bacteria adhesion compared with controls.

    “The 10 wt% SNAP/E2As catheters exhibited enhanced hemocompatibility (70% less thrombus formation) and bactericidal activity (90% reduction of bacteria adhesion) when compared to the controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [186] Brisbois EJ Davis RP Jones AM Major TC Bartlett RH Meyerhoff ME Handa H J Mater. Chem. B 2015 3 1639 1645 PMC4326019 25685358

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  • May combine two claims.

    Premisecitation

    SNAP modified purified gelatin can release NO up to 1 × 10−8 μmol mg−1 s−1 under 527 nm LED light, with continuous light intensity-responsive NO release over 24 h and a total payload of 0.06 μmol NO mg−1.

    “SNAP modified purified gelatin can release NO up to 1 × 10−8 µmol mg−1 s−1 under a 527 nm wavelength light-emitting diode (LED,) and it also shows continuous and light intensity-responsive NO release over 24 h, with a total payload of 0.06 µmol NO mg−1.222”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [222] Vogt C Xing Q He W Li B Frost MC Zhao F Biomacromolecules 2013 14 2521 2530 23844781

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    NO release or generating polymers have demonstrated very positive effects in preventing both platelet activation and thrombus formation and in exhibiting significant antimicrobial activity toward infection and biofilm formation without bacterial resistance.

    “However, NO release or generating polymers have demonstrated very positive effects in terms of preventing both platelet activation and thrombus formation as well as exhibiting significant antimicrobial activity toward infection/biofilm formation without bacterial resistance.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    The remaining challenge for NO delivery polymers for clinical settings lies in developing more stable NO donors and polymer scaffolds and delivering the desired amount of NO in a controlled spatial and temporal manner.

    “The remaining challenge for NO delivery polymers in order to be used in clinical settings lies in the development of more stable NO donors and polymer scaffolds and delivering the desired amount NO in a controlled spatial and temporal manner.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    GSNO-doped chitosan films exerted strong antimicrobial activity against a broad spectrum of bacteria and, as a wound dressing on full thickness excisional wounds in rats for 15 d, treated wounds were almost completely healed with less bacterial burden, decreased inflammatory cell infiltration, and enhanced re-epithelialization.

    “Comparing the NO-treated and untreated wounds, those treated with the GSNO/Chitosan dressing were almost completely healed at the end of the 15 d, with less bacterial burden and decreased inflammatory cell infiltration, but enhanced re-epithelialization.120,221”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [120] Jen MC Serrano MC van Lith R Ameer GA Adv. Funct. Mater 2012 22 239 260 25067935 PMC4111277

      Not checked in the free run.

    • cites [221] Kim JO Noh JK Thapa RK Hasan N Choi M Kim JH Lee JH Ku SK Yoo JW Int. J. Biol. Macromol 2015 79 217 225 25957720

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    In many cases, long-term NO release is desired, especially for NO-releasing blood compatible polymeric materials for intravascular grafts, stents, catheters, and other vascular access devices.

    “In many cases, long-term NO release is desired, especially for using NO-releasing, blood compatible polymeric materials for preparing intravascular grafts, stents, catheters, and other vascular access devices.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NO release polymers also have many other potential applications for skin, bones, connective tissue, gastroenterology, or studying NO-induced cellular responses.

    “Although this review mainly focused on the use of NO release polymers for antithrombotic and antibacterial applications, these polymers also have many other potential applications for use on skin, bones, connective tissue, gastroenterology, or studying NO-induced cellular responses.111,177,294,295”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [111] Nichols SP Storm WL Koh A Schoenfisch MH Adv. Drug Deliv. Rev 2012 64 1177 1188 22433782 PMC3383916

      Not checked in the free run.

    • cites [177] Seabra AB Beck R Guterres S Pohlmann A Nanocosmetics and Nanomedicines 2011 Berlin, Heidelberg Springer Berlin Heidelberg 253 268

      Not checked in the free run.

    • cites [294] Richardson G Benjamin N 2002 105 99 105 11749666

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    DBHD/N2O2 and PLGA doped PU films used as burn wound dressings in mice produced a 4-log unit bacterial reduction compared with control wounds after 24 h treatment.

    “A 4-log unit bacterial reduction was observed for the NO treated wounds when compared to the control would sites.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [290] Brisbois EJ Bayliss J Wu J Major TC Xi C Wang SC Bartlett RH Handa H Meyerhoff ME Acta Biomater 2014 4136 4142 24980058 PMC4160367

      Not checked in the free run.

108 of 108

  • The paper relies on this without support.

    NO has a short half-life in vivo, on the order of seconds, because it reacts rapidly with oxyhemoglobin, oxygen, and thiols.

    “Since NO is highly active in vivo (with a short-half life on the order of seconds due to its rapid reaction with oxyhemoglobin, oxygen, and thiols, etc.)”

  • The paper relies on this without support.

    Device-related infections arise from bacteria adhering to biomaterial surfaces.

    “Device-related infections are the result of bacteria adhesion to the biomaterial surface.”

  • The paper relies on this without support.

    Thrombus and biofilm formation cause device failure that often requires device removal and replacement.

    “Thrombus and bacteria biofilm formation cause device failure, which in many cases can only be solved by device removal and replacement.”

  • The paper relies on this without support.

    The EPS layer acts as a physical and chemical barrier that slows antibiotic penetration enough to make conventional antibiotic treatment ineffective.

    “Of note, the EPS is both a physical and a chemical barrier to antibiotics and significantly retards their rate of penetration that makes conventional antibiotic treatment for such infections ineffective.”

  • The paper relies on this without support.

    The first step that initiates the coagulation cascade is protein adsorption, especially fibrinogen and von Willebrand factor, onto blood-contacting device surfaces.

    “It is widely known that the first step that initiates activation of the coagulation cascade is protein adsorption (especially fibrinogen and von Willebrand factor; see Figure 2) to the surface of a blood contacting medical device.”

  • The paper relies on this without support.

    Bacterial attachment to device surfaces is the first step required for biofilm formation.

    “Bacteria attachment to device surfaces is the first step required for biofilm formation.”

  • The paper relies on this without support.

    Bacteria in mature biofilms are much harder to eradicate than bacteria in the planktonic stage.

    “Further, it is also well known that bacteria in mature biofilms are much harder to eradicate than when they are in planktonic stage.”

  • The paper relies on this without support.

    The need for systemic anticoagulation in extracorporeal procedures can be problematic, particularly in patients with heparin-induced thrombocytopenia.

    “The need for systemic anticoagulation in each of these extracorporeal procedures can be problematic, particularly in patients that have heparin induced thrombocytopenia (HIT).”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Reactive nitrogen species, most importantly nitric oxide radical •NO, peroxynitrite ONOO- and its derivatives, are harmful to microorganisms, including bacteria, viruses, and parasites.

    “Reactive nitrogen species RNS (the most important are nitric oxide radical -•NO, peroxynitrite ONOO— and its derivatives), are also harmful to microorganisms, including bacteria, viruses, and parasites.”

    From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [119]

  • •NO can lyse various bacteria, viruses, fungi, and parasites due to the formation of products such as peroxynitrite, NONOates, S-nitrosothiols, and nitrous acid.

    “•NO can lyse various bacteria, viruses, fungi, and parasites due to the formation of products such as peroxynitrite, NONOates, S-nitrosothiols, and nitrous acid [119].”

    From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [119]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Chitosan treatment is later called a dendrimer

    Minor

    The experiment identifies the NO-releasing material as a chitosan oligosaccharide, but the reported bactericidal concentration is attributed to a dendrimer preparation.

  • Cited reference does not match the named authors

    Minor

    The chitosan-sponge study is attributed to Jennings et al. with citation 67, but reference 67 lists Sepehr and colleagues instead.

2 of 2

Cites

Flagged first, then by citations

2 of the 299 references couldn’t be matched to a known paper.

Research works printed but not linked: 20

  1. Abad, 2011, Infect. Dis. Spec. Ed.
  2. Warkentin, 1992, J. Lab. Clin. Med., 120, 371
  3. Lin, 1987, ASAIO Trans., 33, 602
  4. Mowery, 2000, Polymer, 21, 9
  5. Sepehr, 2014, PLoS One, 9
  6. Wu, 2015, Int. J. Nanomed., 10, 7241
  7. Taite, 2007, J. Biomed. Mater. Res., Part B, 84, 108
  8. Vaughn, 1998, Am. J. Physiol., 274, 2163
  9. Lundberg, 2008, Crit. Care Med., 7, 156
  10. Aravindakumar, 2009, Adv. Phys. Chem., 2009
  11. Holmes, 2000, J. Chem. Soc., Trans. 2, 1639
  12. de Oliveira, 2016, Basic Clin. Pharmacol. Toxicol.
  13. Borthwick, 1980, J. Lab. Clin. Med., 95, 575
  14. Parameshvara, 1967, Br. J. Ind. Med., 24, 73
  15. Jones, 1978, Res. Commun. Chem. Pathol. Pharmacol., 22, 581
  16. Rothrock, 2005, Society, 127, 9362
  17. Storm, 2014, J. Biomed. Mater. Res., Part A, 1
  18. Wan, 2008, J. Mater. Sci. Mater. Med., 20, 321, 10.1007/s10856-008-3511-5 · DOI · Paper page
  19. Vumma, 2015, J. Antibiot., 1
  20. McMullin, 2005, Respir. Care, 50, 1451

Cited by

Sorted by citations

Related

Authors
Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E.
Affiliations
University of Michigan (US)
Corresponding author
Meyerhoff, Mark E.
ORCID
Venue
Biomaterials Science
Publisher
Royal Society of Chemistry (RSC)
Published
2016
Volume
4
Issue
8
Pages
1161-1183
ISSN
  • 2047-4830 (ISSN-L)
  • 2047-4849
DOI
10.1039/c6bm00271d
PMC
PMC4955746
OpenAlex
W2398868795
Semantic Scholar
4709b163ca2d816057af6a9d78682cae0491b0cc
Cited by
251
References
299
Citations by year
2026: 14 · 2025: 14 · 2024: 19 · 2023: 30 · 2022: 34 · 2021: 30 · 2020: 30 · 2019: 30 · 2018: 30 · 2017: 16 · 2016: 3
FWCI
1.47
Type
journal article
Language
en
Open access
Locations
  • Biomaterials Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (HL-119403, HL-128337)
Topics
  • Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
Keywords
nitric oxide, antimicrobial polymers, antithrombotic materials, antibacterial materials, biomedical devices, thrombus formation, bacterial infection, nitric oxide donors, N-diazeniumdiolates, NONOates, S-nitrosothiols, platelet activation, bacterial adhesion
MeSH terms
Animals, Anti-Bacterial Agents, Azo Compounds, Bacterial Adhesion, Fibrinolytic Agents, Humans, Nitric Oxide, Polymers, Thrombosis, Platelet Activation, Nitric Oxide Donors, Coated Materials, Biocompatible, S-Nitrosothiols, Biofouling

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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