Invitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

Handa, Hitesh; Brisbois, Elizabeth J.; Major, Terry C.; Refahiyat, Lahdan; Amoako, Kagya A.; Annich, Gail M.; Bartlett, Robert H.; Meyerhoff, Mark E.

doi:10.1039/c3tb20277a

Cited by 59 publications

(99 citation statements)

References 46 publications

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“…Gaseous nitric oxide treatments and NO releasing materials have been used topically and shown to increase dermal blood flow, increase reepithelialization and angiogenesis, and accelerate wound repair; however, some of these studies have been conducted with uninfected wounds [41-45]. Previous studies have shown NO can be released from polymer films doped with diazeniumdiolate dibutylhexanediamine (DBHD/N 2 O 2 ), which releases NO through proton or thermal driven mechanisms [46-49]. However, the loss of NO from DBHD/N 2 O 2 creates free lipophilic amine species within the polymer that react with water, thereby increasing the pH within the polymer phase and effectively turning off the NO release.…”

Section: Introductionmentioning

confidence: 99%

“…However, the loss of NO from DBHD/N 2 O 2 creates free lipophilic amine species within the polymer that react with water, thereby increasing the pH within the polymer phase and effectively turning off the NO release. In a recent report, poly(lactic-co-glycolic) acid was used as an additive to promote and prolong the NO release from poly(vinyl chloride) films doped with DBHD/N 2 O 2 [49, 50]. The ester linkages of the PLGA will hydrolyze in the presence of water, producing lactic and glycolic acids that can act as proton sources to promote the NO release from DBHD/N 2 O 2 -doped polymers.…”

Section: Introductionmentioning

confidence: 99%

“…Lactate has been shown to enhance angiogenesis and accelerate wound healing [51], so any lactic acid monomers that leach from the NO releasing patches may also prove beneficial. Previous work with DBHD/N 2 O 2 -based films have primarily utilized hydrophobic polymers (e.g., PVC) as the base polymer [46, 49]. In this study, we compared the effects of the base polymer, in terms of their water uptake property, on the NO release from polymer films doped with DBHD/N 2 O 2 and PLGA.…”

Section: Introductionmentioning

confidence: 99%

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Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Brisbois

Bayliss

et al. 2014

Acta Biomaterialia

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Nitric oxide (NO) has many biological roles (e.g., antimicrobial agent, promoter of angiogenesis, prevention of platelet activation, etc.) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2 ± 0.7 wt %) and Tecophillic SP-60D-20 (22.5 ± 1.1 wt%)) were doped with 25 wt% DBHD/N2O2 and 10 wt% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (~4 log reduction). The NO release patches are also able to reduce the TGF-β levels, in comparison to controls, which can enhance reepithelialization, decrease scarring, and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Brisbois

Bayliss

et al. 2014

Acta Biomaterialia

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“…23 This data is consistent with previously reported animal data, where it was shown that NO release is not compromised due to blood exposure. 31,33 The hemocompatibility of these catheters likely could be further improved by exploring methods to increase the NO flux from the SNAP/E2As polymer, perhaps by adding polymeric additives that increase the degree of water uptake by the E2As polymer.…”

Section: Evaluation Of Thrombus Formation and Bacterial Adhesion On Cmentioning

confidence: 99%

“…24,[27][28][29] NO-releasing polymers have been shown to preserve platelet count and reduced thrombus formation when tested in a 4 h rabbit model of extracorporeal circulation (ECC) thrombogenicity. [30][31][32][33][34] I-nitrosothiol-modified xerogels were shown to significantly reduce adhesion of platelets and bacteria (Pseudomonas aeruginosa) when tested in vitro. 35,36 Diazeniomdiolate-doped poly(lactic-co-glycolic acid)-based films exhibited antibiofilm properties against both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria when tested using a drip-flow bioreactor over a 7 d period.…”

Section: Introductionmentioning

confidence: 99%

Reduction in thrombosis and bacterial adhesion with 7 day implantation of S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As catheters in sheep

et al. 2015

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Thrombosis and infection are two common problems associated with blood-contacting medical devices such as catheters. Nitric oxide (NO) is known to be a potent antimicrobial agent as well as an inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5~4×10 −10 mol cm −2 min −1 that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, NO-releasing catheters were fabricated by incorporating S-nitroso-N-acetylpenicillamine (SNAP) in the Elast-eon E2As polymer. The SNAP/E2As catheters release physiological levels of NO for up to 20 d, as measured by chemiluminescence. Furthermore, SNAP is stable in the E2As polymer, retaining 89% of the initial SNAP after ethylene oxide (EO) sterilization. The SNAP/E2As and E2As control catheters were implanted in sheep veins for 7 d to examine the effect on thrombosis and bacterial adhesion. The SNAP/E2As catheters reduced the thrombus area when compared to the control (1.56 ± 0.76 and 5.06 ± 1.44 cm 2 , respectively). A 90% reduction in bacterial adhesion was also observed for the SNAP/E2As catheters as compared to the controls. The results suggest that the SNAP/E2As polymer has the potential to improve the hemocompatibility and bactericidal activity of intravascular catheters, as well as other blood-contacting medical devices (e.g., vascular grafts, extracorporeal circuits).

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Multi‐Modal, Surface‐Focused Anticoagulation Using Poly‐2‐methoxyethylacrylate Polymer Grafts and Surface Nitric Oxide Release

Gupta

Amoako

Suhaib

et al. 2014

Adv Materials Inter

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and platelet activation on the surfaces of these devices lead to clot formation. This, in turn, causes device failure and thromboembolic complications. The most common solution to this problem is systemic anticoagulation, but this leads to bleeding complications that can also contribute to patient morbidity and mortality. [ 1-3 ] Anticoagulation that is limited only upon device surfaces could remedy these shortcomings. Two methods of surface focused anticoagulation have demonstrated some promise in reducing coagulation: surface coatings designed to limit nonspecifi c protein adsorption and anti-platelet surface NO release. Surface coatings only reduce coagulation in the device and thus have no systemic anticoagulant effect. Various commercial anti-thrombogenic coatings have shown better preservation of platelet counts than the uncoated control surface [ 4,5 ] during short-term applications. However, these surface coatings have not yet proven suffi cient to allow the elimination of systemic anticoagulation or long-term use of high surface area artifi cial organs without signifi cant decrease in systemic platelet concentration. [ 6,7 ] Nitric oxide is released from biomaterials into fl owing blood, [ 8-12 ] but has a short half-life of 2-5 seconds [ 8 ] in blood prior to being scavenged. Thus, its systemic effects are minor, and it has been examined as a means to focus anticoagulation at biomaterials' surfaces rather than systemically. Several means of supplying surface NO fl ux have been tested. They include NO release from a stored pool in the biomaterial, NO generation from endogenous sources in blood, and NO delivery via the gas fl ow in artifi cial lungs. [ 9-12 ] Early studies examining the latter approach were largely unsuccessful. These studies did not quantify surface NO fl ux, and it was likely insuffi cient. [ 13 ] More recent studies with proven, endothelial levels of NO fl ux (>2 × 10 −10 mol/min/cm 2) have been successful, reducing platelet adhesion in tubing and catheters by approximately 40%, [ 9,10 ] and markedly reducing coagulation and increasing longevity in artifi cial lungs. [ 12 ] Although positive, these studies were all for a period of 4 hours. Longer-term effectiveness in these settings is unknown. Additionally, use of NO in high surface area artifi cial organs could lead to excessive generation of methemoglobin in the blood, limiting the possible fl ux rates, and anticoagulation. In this study, we hypothesize that the combination of antiadsorptive coatings and surface NO fl ux will lead to more This study examines platelet adhesion on surfaces that combine coatings to limit protein adsorption along with "anti-platelet" nitric oxide (NO) release. Uncoated and poly-2-methoxyethylacrylate (PMEA) coated, gas permeable polypropylene (PP) membranes were placed in a bioreactor to separate plasma and gas fl ows. Nitrogen with 100/500/1000 ppm of NO was supplied to the gas side as a proof of concept. On the plasma side, platelet rich plasma (PRP, 1 × 108 cell/mL) was recirculated at low (60)/high ...

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Invitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

Cited by 59 publications

References 46 publications

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Reduction in thrombosis and bacterial adhesion with 7 day implantation of S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As catheters in sheep

Multi‐Modal, Surface‐Focused Anticoagulation Using Poly‐2‐methoxyethylacrylate Polymer Grafts and Surface Nitric Oxide Release

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