Manuka Honey Reduces NETosis on an Electrospun Template Within a Therapeutic Window.

Benjamin A Minden-Birkenmaier,Marko Z Radic,Richard A Smith,Marie Van Der Merwe,Gary L Bowlin

doi:10.3390/polym12061430

Benjamin A Minden-Birkenmaier, Marko Z Radic + Show 3 more

Open Access

https://doi.org/10.3390/polym12061430

Copy DOI

Abstract

Manuka honey, a topical wound treatment used to eradicate bacteria, resolve inflammation, and promote wound healing, is a focus in the tissue engineering community as a tissue template additive. However, its effect on neutrophil extracellular trap formation (NETosis) on a tissue engineering template has yet to be examined. As NETosis has been implicated in chronic inflammation and fibrosis, the reduction in this response within the wound environment is of interest. In this study, Manuka honey was incorporated into electrospun templates with large (1.7–2.2 µm) and small (0.25–0.5 µm) diameter fibers at concentrations of 0.1%, 1%, and 10%. Template pore sizes and honey release profiles were quantified, and the effect on the NETosis response of seeded human neutrophils was examined through fluorescence imaging and myeloperoxidase (MPO) analysis. The incorporation of 0.1% and 1% Manuka honey decreased NETosis on the template surface at both 3 and 6 h, while 10% honey exacerbated the NETosis response. Additionally, 0.1% and 1% Manuka honey reduced the MMP-9 release of the neutrophils at both timepoints. These data indicate a therapeutic window for Manuka honey incorporation into tissue engineering templates for the reduction in NETosis. Future in vivo experimentation should be conducted to translate these results to a physiological wound environment.

Highlights

The implantation of a biomaterial tissue engineering template into the body initiates an orchestrated series of events which have important ramifications on the ultimate success or failure of that template.Immediately, proteins in the pooled blood around the template begin to adsorb to its surface, altering its properties [1]
As honey neutrophils are oneon ofneutrophil the first inflammatory typesofto with an implanted material, one of the first inflammatory cell types to interact with an implanted material, and the NETosis and the NETosis response is an important predictor of the degree of fibrosis surrounding this material, response is an important predictor of the degree of fibrosis surrounding this material, assessing this assessing this response is crucial to predicting the success or failure of honey-laden tissue engineering response is crucial to predicting the success or failure of honey-laden tissue engineering templates
The degree of neutrophil NETosis on a tissue engineering template is predictive of the degree of fibrosis it will encounter in vivo, and its success or failure to integrate with the surrounding tissue and induce regeneration

Summary

Introduction

The implantation of a biomaterial tissue engineering template into the body initiates an orchestrated series of events which have important ramifications on the ultimate success or failure of that template.Immediately, proteins in the pooled blood around the template begin to adsorb to its surface, altering its properties [1]. As the first-responders, these cells play a key role in the preconditioning of the template surface and surrounding microenvironment that influences the ultimate fate of the tissue engineering template In addition to their roles as a phagocyte and a producer of cyto/chemokines, neutrophils have the ability to eject a mixture of DNA and bactericidal granular components to create neutrophil extracellular traps (NETs) during a cell death process known as NETosis [4]. The intracellular responses to these signals increase the production of intracellular reactive oxygen species, which activate an enzyme known as PAD4 to citrullinate histone H3 [5] Citrullination of these histones causes the chromatin to decondense, which leads to the collapse of the nuclear membrane, adsorption of granular components by the chromatin, rupture of the plasma membrane, and NET release. It is of interest to develop methods of regulating NETosis on the surface of these tissue engineering templates to improve tissue-template integration and subsequent tissue regeneration

Methods

Results

Discussion

Conclusion