Reactive oxygen species scavenging with a biodegradable, thermally responsive hydrogel compatible with soft tissue injection

Zhu, Yang; Matsumura, Yasumoto; Murugesan, V.; Foley, Lesley M.; Hitchens, T. Kevin; Wagner, William R.

doi:10.1016/j.biomaterials.2018.05.044

Cited by 143 publications

(109 citation statements)

References 54 publications

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“…Therefore, future studies in this model could increase the oral drug dosage to achieve higher concentrations of active drug in the heart prior to assessing cardio-protection through the antioxidant and anti-inflammatory pathways we have assessed. This assertion is further supported by a novel study which has compared modes of delivery of a nitroxide either directly injected into the heart or delivered covalently bonded to a thermally responsive hydrogel which ensured drug longevity and prolonged drug scavenging properties [ 41 ]. The authors reported that the hydrogel conjugated nitroxide showed a decrease in IL-1b secretion, a decrease in apoptosis, and improved cardiac functioning measured as increased left ventricular end diastolic volume [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…This assertion is further supported by a novel study which has compared modes of delivery of a nitroxide either directly injected into the heart or delivered covalently bonded to a thermally responsive hydrogel which ensured drug longevity and prolonged drug scavenging properties [ 41 ]. The authors reported that the hydrogel conjugated nitroxide showed a decrease in IL-1b secretion, a decrease in apoptosis, and improved cardiac functioning measured as increased left ventricular end diastolic volume [ 41 ]. This suggests that a strategy to increase drug concentration and half-life results in an improved cardio-protection, and many studies are currently researching new ways to increase the potency of nitroxides in vivo through this mechanism [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

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Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

Kazzi

Shi

Vuong

et al. 2020

IJMS

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Reperfusion therapy increases survival post-acute myocardial infarction (AMI) while also stimulating secondary oxidant production and immune cell infiltration. Neutrophils accumulate within infarcted myocardium within 24 h post-AMI and release myeloperoxidase (MPO) that catalyses hypochlorous acid (HOCl) production while increasing oxidative stress and inflammation, thereby enhancing ventricular remodelling. Nitroxides inhibit MPO-mediated HOCl production, potentially ameliorating neutrophil-mediated damage. Aim: Assess the cardioprotective ability of nitroxide 4-methoxyTEMPO (4MetT) within the setting of AMI. Methods: Male Wistar rats were separated into 3 groups: SHAM, AMI/R, and AMI/R + 4MetT (15 mg/kg at surgery via oral gavage) and subjected to left descending coronary artery ligation for 30 min to generate an AMI, followed by reperfusion. One cohort of rats were sacrificed at 24 h post-reperfusion and another 28 days post-surgery (with 4MetT (15 mg/kg) administration twice daily). Results: 3-chlorotyrosine, a HOCl-specific damage marker, decreased within the heart of animals in the AMI/R + 4-MetT group 24 h post-AMI, indicating the drug inhibited MPO activity; however, there was no evident difference in either infarct size or myocardial scar size between the groups. Concurrently, MPO, NfκB, TNFα, and the oxidation marker malondialdehyde increased within the hearts, with 4-MetT only demonstrating a trend in decreasing MPO and TNF levels. Notably, 4MetT provided a significant improvement in cardiac function 28 days post-AMI, as assessed by echocardiography, indicating potential for 4-MetT as a treatment option, although the precise mechanism of action of the compound remains unclear.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

Kazzi

Shi

Vuong

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…[ 79 ] To circumvent the inflammatory damage of ROS, Wagner and co‐workers developed a thermally responsive injectable hydrogel with pendant 4‐amino‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl groups that incorporate recyclable nitroxide radical scavengers. [ 80 ] Application in an ischemia/reperfusion model reduced oxidative injury of localized inflammation. Success of these biointeractive approaches to control of the local environment through immobilized agents presents opportunity for the cell–biomaterial interface through biomimetic approaches.…”

Section: Material‐based Modulation Of Inflammatory Behaviormentioning

confidence: 99%

Advanced Strategies for Modulation of the Material–Macrophage Interface

Huyer

Pascual-Gil

Wang

et al. 2020

Adv Funct Materials

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Biomaterials are becoming increasingly crucial for healthcare solutions, with extensive use in the field of tissue engineering and drug delivery. After implantation, biomaterials trigger an immune response characterized by the recruitment of bone-marrow-derived proinflammatory macrophages that develop as the most abundant cell type surrounding the biomaterial. Chronic activation of this recruited macrophage population induces a foreign body reaction response and consequent biomaterial rejection. However, transition toward a proreparative phenotype is associated with biomaterial integration and tissue homeostasis restoration. In this review, the most relevant strategies that modulate biomaterial immune response are discussed, including mechanical properties, surface coatings, release of anti-inflammatory molecules and cytokines, antibacterial features, origin and inner moieties of biomaterials, and cell crosstalk. Moreover, the role of tissue resident macrophages, an embryo-derived macrophage population with a strong reparative potential, in promoting biomaterial tolerance will be reviewed. This provides new insights to better tune the reaction of the host immune system to implanted biomaterials in order to favor integration and increase the knowledge of macrophages as key players in tissue homeostasis.

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“…In addition to ROS-triggered drug release, polymers with ROS-responsive bonds in their backbones or side chains are capable of consuming the excessive ROS produced by the MI. This reduces injury to the cardiac tissue, and has the potential for preventing and treating cardiovascular disease [133][134][135]. Yao et al reported a biodegradable elastomeric polyurethanes (PUTK) with ROS-responsive properties, which they made fibrous patches from.…”

Section: Inflammatory-responsive Drug Releasementioning

confidence: 99%

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Askari

Seyfoori

Amereh

et al. 2020

Gels

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Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

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Reactive oxygen species scavenging with a biodegradable, thermally responsive hydrogel compatible with soft tissue injection

Cited by 143 publications

References 54 publications

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

Advanced Strategies for Modulation of the Material–Macrophage Interface

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

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