Inducible nitric oxide releasing poly-(ethylene glycol)-fibrinogen adhesive hydrogels for tissue regeneration

2013 ◽  
Vol 1569 ◽  
pp. 39-44 ◽  
Author(s):  
Margaret Brunette ◽  
Hal Holmes ◽  
Michael G. Lancina ◽  
Weilue He ◽  
Bruce P. Lee ◽  
...  

ABSTRACTNitric oxide (NO) release can promote healthy tissue regeneration. A PEG-fibrinogen adhesive hydrogel that would allow for inducible NO release was created with mechanical properties that could be tailored to specific applications and tissue types. PEG (4-arm)-fibrinogen hydrogels of varying ratios were derivatized with S-nitroso-N-acetyl-D, L-penicillamine (SNAP)-thiolactone to create an active NO donor material. Controlled release from gels was established using light as the activating source, although temperature, pH, and external mechanical loading are also means to induce active NO release. Gels with varying ratios of fibrinogen to PEG were made, derivatized, and tested. Gels below a ratio of 1.5:1 (fibrinogen:PEG) did not gel, while at ratio of 1.5:1 gelation occurs and NO release can be induced. Interestingly, the release from 1.5:1 gels was significantly lower compared to 2:1 and 3:1 gel formulations. Rheometric data show that lower ratio gels are more elastic than viscous. Derivatized gels exhibited linear elastic moduli, behaving more like other more synthetic hydrogels. Swelling data indicates that as the ratio of fibrinogen to PEG increases the swelling ratio decreases, likely due to the hydrophobic nature of the NO donor. Cells remain viable on both derivatized and non-derivatized gels.

2011 ◽  
Vol 340 ◽  
pp. 363-368 ◽  
Author(s):  
Xiao Qing Zou ◽  
Yong Lan Ding ◽  
Sheng Ming Peng ◽  
Chang Ping Hu ◽  
Han Wu Deng ◽  
...  

Angiogenesis, the development of new capillaries from pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate to form functional vessels. Endothelial dysfunction and decreased nitric oxide bioavailability may underscore the impairment of angiogenesis. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to therapeutic angiogenesis. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited promotion of endothelial migration and tubulogenesis in vitro as well as stimulation angiogenesis in vivo.Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4 and enhanced VEGF secretion and VEGF mRNA expression of endothelial cells. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for angiogenesis deficiency due to ischemic diseases.


2020 ◽  
Vol 11 (1) ◽  
pp. 186-194 ◽  
Author(s):  
Yutian Duan ◽  
Yong Wang ◽  
Xiaohu Li ◽  
Guozhen Zhang ◽  
Guoying Zhang ◽  
...  

Nitric oxide-releasing amphiphiles are successfully synthesized through direct polymerization and are engineered as photoresponsive polymersomes for biomedical applications.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1445
Author(s):  
Daniel C. Wang ◽  
Justin R. Clark ◽  
Richard Lee ◽  
Adam H. Nelson ◽  
Anthony W. Maresso ◽  
...  

Nitric oxide (NO) is a highly reactive gas molecule, exhibiting antimicrobial properties. Because of its reactive nature, it is challenging to store and deliver NO efficiently as a therapeutic agent. The objective of this study was to develop NO-releasing polymeric fibers (NO-fibers), as an effective delivery platform for NO. NO-fibers were fabricated with biopolymer solutions of polyvinyl pyrrolidone (PVP) and ethylcellulose (EC), and derivatives of N-diazeniumdiolate (NONOate) as NO donor molecules, using an electrospinning system. We evaluated in vitro NO release kinetics, along with antimicrobial effects and cytotoxicity in microorganisms and human cell culture models. We also studied the long-term stability of NONOates in NO-fibers over 12 months. We demonstrated that the NO-fibers could release NO over 24 h, and showed inhibition of the growth of Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA), without causing cytotoxicity in human cells. NO-fibers were able to store NONOates for over 12 months at room temperature. This study presents the development of NO-fibers, and the feasibility of NO-fibers to efficiently store and deliver NO, which can be further developed as a bandage.


2015 ◽  
Vol 6 (44) ◽  
pp. 7737-7748 ◽  
Author(s):  
Tengjiao Wang ◽  
André J. van der Vlies ◽  
Hiroshi Uyama ◽  
Urara Hasegawa

Polymeric nitric oxide (NO) donors were prepared by the conjugation of the azide-containing furoxans and poly(ethylene glycol) having an alkyne end groupviathe copper-catalyzed Huisgen cycloaddition.


2016 ◽  
Vol 4 (3) ◽  
pp. 422-430 ◽  
Author(s):  
Alex R. Ketchum ◽  
Michael P. Kappler ◽  
Jianfeng Wu ◽  
Chuanwu Xi ◽  
Mark E. Meyerhoff

Silicone rubber catheters impregnated with S-nitroso-tert-dodecylmercaptan demonstrate long term NO release, minimal leaching, considerable antimicrobial activity, and reasonable storage stability.


2005 ◽  
Vol 390 (2) ◽  
pp. 625-631 ◽  
Author(s):  
Antonius C. F. Gorren ◽  
Michael Russwurm ◽  
Alexander Kollau ◽  
Doris Koesling ◽  
Kurt Schmidt ◽  
...  

GTN (nitroglycerin; glycerol trinitrate) causes dilation of blood vessels via activation of nitric oxide (NO)-sensitive sGC (soluble guanylate cyclase), a heterodimeric haem protein that catalyses the conversion of GTP into cGMP. Activation of sGC by GTN requires enzymatic or non-enzymatic bioactivation of the nitrate. Based on insufficient NO release and lack of spectroscopic evidence for formation of NO–sGC, the cysteine (Cys)-dependent activation of sGC by GTN was proposed to occur in an NO-independent manner. This extraordinary claim is questioned by the present findings. First, the effect of GTN/Cys was blocked by the NO scavenger oxyhaemoglobin, the superoxide-generating compound flavin mononucleotide and the haem-site sGC inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Secondly, at equi-effective concentrations, GTN/Cys and the NO donor 2,2-diethyl-1-nitroso-oxyhydrazine released identical amounts of NO. Finally, at sufficiently high rates of NO release, activation of sGC by GTN/Cys was accompanied by a shift of the Soret band from 431 to 399 nm, indicating formation of NO–sGC. In the absence of Cys, GTN caused haem oxidation, apparent as a shift of the Soret band to 392 nm, which was accompanied by inactivation of the NO-stimulated enzyme. These results suggest that the effect of GTN/Cys is the result of an activation/inactivation equilibrium that is controlled by the rate of NO release and haem oxidation.


2017 ◽  
Vol 5 (7) ◽  
pp. 1265-1278 ◽  
Author(s):  
Yaqi Wo ◽  
Li-Chong Xu ◽  
Zi Li ◽  
Adam J. Matzger ◽  
Mark E. Meyerhoff ◽  
...  

SNAP-impregnated textured polymer films having up to 38 day NO-release were shown to have synergistic effects in inhibiting bacterial adhesion.


2000 ◽  
Vol 92 (6) ◽  
pp. 1677-1684 ◽  
Author(s):  
Ingeborg D. Welters ◽  
Axel Menzebach ◽  
Yannick Goumon ◽  
Patrick Cadet ◽  
Thilo Menges ◽  
...  

Background The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils. Methods The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used. Results Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release. Conclusion Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.


2017 ◽  
Vol 15 (13) ◽  
pp. 2791-2796 ◽  
Author(s):  
Hana Okuno ◽  
Naoya Ieda ◽  
Yuji Hotta ◽  
Mitsuyasu Kawaguchi ◽  
Kazunori Kimura ◽  
...  

A novel yellowish-green-light-controllable NO donor, NO-Rosa, was synthesized. With NO-Rosa, NO release in cells and NO-induced vasodilation were photocontrolled.


Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 22
Author(s):  
Nurhasni Hasan ◽  
Juho Lee ◽  
Hye-Jin Ahn ◽  
Wook Ryol Hwang ◽  
Muhammad Akbar Bahar ◽  
...  

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.


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