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      Honey-Based Templates in Wound Healing and Tissue Engineering

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          Abstract

          Over the past few decades, there has been a resurgence in the clinical use of honey as a topical wound treatment. A plethora of in vitro and in vivo evidence supports this resurgence, demonstrating that honey debrides wounds, kills bacteria, penetrates biofilm, lowers wound pH, reduces chronic inflammation, and promotes fibroblast infiltration, among other beneficial qualities. Given these results, it is clear that honey has a potential role in the field of tissue engineering and regeneration. Researchers have incorporated honey into tissue engineering templates, including electrospun meshes, cryogels, and hydrogels, with varying degrees of success. This review details the current state of the field, including challenges which have yet to be overcome, and makes recommendations for the direction of future research in order to develop effective tissue regeneration therapies.

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          Most cited references106

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          Defensins: antimicrobial peptides of innate immunity.

          Tomas Ganz (2003)
          The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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            Functional properties of honey, propolis, and royal jelly.

            Honey, propolis, and royal jelly, products originating in the beehive, are attractive ingredients for healthy foods. Honey has been used since ancient times as part of traditional medicine. Several aspects of this use indicate that it also has functions such as antibacterial, antioxidant, antitumor, anti-inflamatory, antibrowning, and antiviral. Propolis is a resinous substance produced by honeybees. This substance has been used in folk medicine since ancient times, due to its many biological properties to possess, such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects, among others. Royal jelly has been demonstrated to possess numerous functional properties such as antibacterial activity, anti-inflammatory activity, vasodilative and hypotensive activities, disinfectant action, antioxidant activity, antihypercholesterolemic activity, and antitumor activity. Biological activities of honey, propolis, and royal jelly are mainly attributed to the phenolic compounds such as flavonoids. Flavonoids have been reported to exhibit a wide range of biological activities, including antibacterial, antiviral, anti-inflammatory, antiallergic, and vasodilatory actions. In addition, flavonoids inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and the activity of enzyme systems including cyclo-oxygenase and lipoxygenase.
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              How honey kills bacteria.

              With the rise in prevalence of antibiotic-resistant bacteria, honey is increasingly valued for its antibacterial activity. To characterize all bactericidal factors in a medical-grade honey, we used a novel approach of successive neutralization of individual honey bactericidal factors. All bacteria tested, including Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli, ciprofloxacin-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium, were killed by 10-20% (v/v) honey, whereas > or = 40% (v/v) of a honey-equivalent sugar solution was required for similar activity. Honey accumulated up to 5.62 +/- 0.54 mM H(2)O(2) and contained 0.25 +/- 0.01 mM methylglyoxal (MGO). After enzymatic neutralization of these two compounds, honey retained substantial activity. Using B. subtilis for activity-guided isolation of the additional antimicrobial factors, we discovered bee defensin-1 in honey. After combined neutralization of H(2)O(2), MGO, and bee defensin-1, 20% honey had only minimal activity left, and subsequent adjustment of the pH of this honey from 3.3 to 7.0 reduced the activity to that of sugar alone. Activity against all other bacteria tested depended on sugar, H(2)O(2), MGO, and bee defensin-1. Thus, we fully characterized the antibacterial activity of medical-grade honey.
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                Author and article information

                Journal
                Bioengineering (Basel)
                Bioengineering (Basel)
                bioengineering
                Bioengineering
                MDPI
                2306-5354
                14 June 2018
                June 2018
                : 5
                : 2
                : 46
                Affiliations
                Department of Biomedical Engineering, University of Memphis, 3806 Norriswood Ave., Memphis, TN 38152, USA; bmndnbrk@ 123456memphis.edu
                Author notes
                [* ]Correspondence: glbowlin@ 123456memphis.edu ; Tel.: +1-(901)-678-2670
                Author information
                https://orcid.org/0000-0003-0917-8203
                Article
                bioengineering-05-00046
                10.3390/bioengineering5020046
                6027142
                29903998
                c2d4dc62-5cab-4b0a-88ed-4f3b4f2985f5
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 March 2018
                : 10 June 2018
                Categories
                Review

                tissue engineering,tissue regeneration,electrospinning,cryogel,hydrogel,manuka honey,chronic wound,inflammation

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