Enzyme mimetic microgel coating for endogenous nitric oxide mediated inhibition of platelet activation

Hosseinnejad, Aisa; Fischer, Thorsten; Jain, Puja; Berne, Christian; Jakob, Felix; Schwaneberg, Ulrich; Rossaint, Rolf; Singh, Smriti

doi:10.1016/j.jcis.2021.05.143

Cited by 15 publications

(12 citation statements)

References 49 publications

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“…Nitric oxide-releasing microgels (NOrel-MGs) were synthesized using N-(2-hydroxypropyl)methacrylamide (HPMA) as a monomer and diselenide-bearing N,N'-bis(methacryloyl)selenocystamine (BMASC) and N,N'-methylenebis(acrylamide) (MBAA) as crosslinkers. The synthesis of HPMA, BMASC and NOrel-MGs was reported in our previous work [29]. Briefly, the microgels were fabricated in an inverse miniemulsion through freeradical emulsion polymerization.…”

Section: Microgel Synthesis and Coatingmentioning

confidence: 99%

“…The recombinant LCI was produced as a fusion protein with a functional block consisting of an enhanced green fluorescent protein (eGFP), bearing the free cysteines fused to the N-terminus of LCI [43]. This facilitated the fluorescent detection of the anchor peptide on the eGFP-LCI-treated surface (Scheme 3a) and covalent attachment of the microgels through the interaction between the eGFP-thiols and the microgel-oxirane moieties introduced by GMA to the microgel structure (Scheme 3b) [29].…”

Section: Norel Microgel Coatingmentioning

confidence: 99%

“…The obtained active species mimics the GPx-like enzymatic function and facilitates the decomposition of the endogenous NO-donors leading to NO-release. To maintain the catalytic cycle, GSH with the generated selenenyl sulfide (RSe-SG) intermediate reproduces the active species of selenol/selenolate [29,[46][47][48] (Figure S3).…”

Section: Mechanism Of Endogenous No-releasementioning

confidence: 99%

“…An enzyme mimetic non-fouling microgel coating for endogenous NO release was recently developed by this group [29]. The microgels with a highly hydrophilic base are incorporated with diselenide crosslinks [30,31].…”

Section: Introductionmentioning

confidence: 99%

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Endogenous Nitric Oxide-Releasing Microgel Coating Prevents Clot Formation on Oxygenator Fibers Exposed to In Vitro Blood Flow

et al. 2022

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Background: Clot formation on foreign surfaces of extracorporeal membrane oxygenation systems is a frequent event. Herein, we show an approach that mimics the enzymatic process of endogenous nitric oxide (NO) release on the oxygenator membrane via a biomimetic, non-fouling microgel coating to spatiotemporally inhibit the platelet (PLT) activation and improve antithrombotic properties. This study aims to evaluate the potential of this biomimetic coating towards NO-mediated PLT inhibition and thereby the reduction of clot formation under flow conditions. Methods: Microgel-coated (NOrel) or bare (Control) poly(4-methyl pentene) (PMP) fibers were inserted into a test channel and exposed to a short-term continuous flow of human blood. The analysis included high-resolution PLT count, pooled PLT activation via β-Thromboglobulin (β-TG) and the visualization of remnants and clots on the fibers using scanning electron microscopy (SEM). Results: In the Control group, PLT count was significantly decreased, and β-TG concentration was significantly elevated in comparison to the NOrel group. Macroscopic and microscopic visualization showed dense layers of stable clots on the bare PMP fibers, in contrast to minimal deposition of fibrin networks on the coated fibers. Conclusion: Endogenously NO-releasing microgel coating inhibits the PLT activation and reduces the clot formation on PMP fibers under dynamic flow.

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Section: Microgel Synthesis and Coatingmentioning

confidence: 99%

Section: Norel Microgel Coatingmentioning

confidence: 99%

Section: Mechanism Of Endogenous No-releasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endogenous Nitric Oxide-Releasing Microgel Coating Prevents Clot Formation on Oxygenator Fibers Exposed to In Vitro Blood Flow

et al. 2022

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“…6,7 The examples discussed above highlight the imperative need to further modify the surface properties of such biomaterials, in particular for advanced blood compatibility. Ways to achieve this focus on rendering the surface hydrophilic (passive approach) and on endowing the surface with active molecules, which inhibit the coagulative response [8][9][10] and eventually even promote re-endothelization (active approach). 11 In order to combine both approaches, an ideal surface modification should consist of a biocompatible hydrogel, to which peptides and proteins do not bind by unspecific adsorption, which, however, can be equipped with specific biofunctional elements like cellspecific ligands, or cytokines and drugs which help to generate a functional natural interface with tissue or blood.…”

Section: Introductionmentioning

confidence: 99%

A facile method for grafting functional hydrogel films on PTFE, PVDF, and TPX polymers

et al. 2022

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NIR Light‐Fuse Drug‐Free Photothermal Armor‐Piercing Microcapsule for Femoral Vein Thrombosis Therapy

Yang,

Qian,

Yuan

et al. 2024

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Acute thrombosis and its complications are leading global causes of disability and death. Existing thrombolytic drugs, such as alteplase and urokinase (UK), carry a significant bleeding risk during clinical treatments. Thus, the development of a novel thrombolysis strategy is of utmost urgency. Based on the previous work, the hollow structure of microcapsules (MC) is fabricated. Subsequently, armor‐piercing MC, known as Fucoidan/S‐Nitrosoglutathione/Melanin@MC (FGM@MC) is obtained, using a layer‐by‐layer (LBL) self‐assembly method. Utilizing near‐infrared (NIR) light as a trigger, the FGM@MC demonstrated photothermal thrombolysis at the site of thrombus due to its stable and outstanding photothermal properties. Simultaneously, photothermal stimulation leads to the release of a significant amount of nitric oxide from the FGM@MC, resulting in cavitation effects for mechanical thrombolysis. In vivo experiments confirmed the stable release of nitric oxide under NIR light irradiation. Treatment of femoral vein thrombosis in rats revealed that the thrombolytic effectiveness of FGM@MC+NIR (53.71%) is comparable to that of UK (59.70%). Notably, FGM@MC does not interfere with the coagulation function of rats and exhibits a favorable safety profile. In conclusion, this study demonstrates that the drug‐free armor‐piercing microcapsule has significant potential in the treatment of thrombosis, offering a safe and effective alternative to traditional thrombolytic therapies.

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Enzyme mimetic microgel coating for endogenous nitric oxide mediated inhibition of platelet activation

Cited by 15 publications

References 49 publications

Endogenous Nitric Oxide-Releasing Microgel Coating Prevents Clot Formation on Oxygenator Fibers Exposed to In Vitro Blood Flow

Endogenous Nitric Oxide-Releasing Microgel Coating Prevents Clot Formation on Oxygenator Fibers Exposed to In Vitro Blood Flow

A facile method for grafting functional hydrogel films on PTFE, PVDF, and TPX polymers

NIR Light‐Fuse Drug‐Free Photothermal Armor‐Piercing Microcapsule for Femoral Vein Thrombosis Therapy

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