MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.

dc.contributor.author

Bellot, Gregory Lucien

dc.contributor.author

Dong, Xiaoke

dc.contributor.author

Lahiri, Amitabha

dc.contributor.author

Sebastin, Sandeep Jacob

dc.contributor.author

Batinic-Haberle, Ines

dc.contributor.author

Pervaiz, Shazib

dc.contributor.author

Puhaindran, Mark Edward

dc.date.accessioned

2020-07-15T22:19:05Z

dc.date.available

2020-07-15T22:19:05Z

dc.date.issued

2019-01

dc.date.updated

2020-07-15T22:19:02Z

dc.description.abstract

Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.

dc.identifier

S2213-2317(18)30524-X

dc.identifier.issn

2213-2317

dc.identifier.issn

2213-2317

dc.identifier.uri

https://hdl.handle.net/10161/21189

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Redox biology

dc.relation.isversionof

10.1016/j.redox.2018.10.014

dc.subject

Animals

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Humans

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Rats

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Disease Models, Animal

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Metalloporphyrins

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Superoxide Dismutase

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Antioxidants

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Treatment Outcome

dc.subject

Combined Modality Therapy

dc.subject

Administration, Topical

dc.subject

Biomimetics

dc.subject

Wound Healing

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Enzyme Activation

dc.subject

Disease Management

dc.subject

Negative-Pressure Wound Therapy

dc.subject

Biological Mimicry

dc.title

MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.

dc.type

Journal article

pubs.begin-page

307

pubs.end-page

320

pubs.organisational-group

School of Medicine

pubs.organisational-group

Radiation Oncology

pubs.organisational-group

Duke

pubs.organisational-group

Clinical Science Departments

pubs.publication-status

Published

pubs.volume

20

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