The effect of fish oil components and manuka honey in models of issues faced in chronic wound treatment

Chronic wounds are becoming an increasing burden on healthcare services as they have extended healing times and are susceptible to infection, with many failing to heal which can lead to amputation. Due to the additional rise in incidence of antimicrobial resistance and emergence of difficult to treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. This work considers how marine based fatty acids (including their metabolites) and manuka honey can act as antimicrobials, as well as how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.

The antimicrobial abilities of the treatments were assessed using developed standardised methods to find their inhibitory, bactericidal and antibiofilm concentrations. Manuka honey was found to be a broad-spectrum treatment, and the high methylglyoxal sample was superior in bactericidal and antibiofilm testing. Docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) were both effective against Gram positive and negative pathogens, but not some drug resistant strains or pathogens protected by a capsule. E. coli was inhibited by all resolvins tested.

A fibroblast scratch wound model was used to measure the effect of the treatments on dermal fibroblasts. The re-coverage of the scratched area was measured together with the level of interleukin-6 due to its association with scar tissue production. High concentrations of all cellular sub-toxic treatments caused impediment to wound healing when compared to an untreated control, though some treatments achieved equivalence to controls within 24 hours of treatment exposure. Production of interleukin-6 was measured with an ELISA, with DHA inhibiting cytokine release and EPA having no significant effect. Manuka honey showed a positive correlation in IL-6 production that increased as the concentration of the honey increased, although the response was not linked to the concentration of MGO.

The work suggests that DHA, EPA, and manuka honey are all worthy of further investigation as potential treatments for wound healing within a clinical setting. They have shown through this work and others to be potent antimicrobials also capable of biofilm eradication, and such treatments are needed due to the rise in antimicrobial resistance. Although scratch recoverage was not improved, the results suggest that the single cell type wound model is not representative of existing in vivo results, particularly in the case of Manuka honey. All proposed treatments require more detailed testing and identification of mechanisms of action.