Honey-Based Templates in Wound Healing and Tissue Engineering

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.

Keywords: Inflammation; Manuka honey; chronic wound; cryogel; electrospinning; hydrogel; tissue engineering; tissue regeneration.

Figure 1

Honeys induce monocyte inflammation response. IL-6, IL-1, and TNF release from peripheral blood monocytes over 18 h in the presence of artificial honey (syrup control), Manuka honey, Pasture honey, and Jelly Bush honey. “*” indicates statistical significance (p < 0.001, analyzed by ANOVA with a Tukey pair-wise comparison). Reproduced with permission from Tonks et al., Cytokine; published by Elsevier, 2003.

Figure 2

Undiluted honey damages cilia. (Top) SEM of saline-exposed chinchilla cochlea, in which normal inner and outer hair cells are observed. (Bottom) SEM of honey-exposed chinchilla cochlea in which the inner and outer hair cells have been damaged. Reproduced with permission from Aron et al., Otolaryngology—Head & Neck Surgery; published by BMC, 2012.

Figure 3

Honey induces fibroblast infiltration. (A) Representative images of H and E-stained honey templates and water controls after 28 days of fibroblast culture. (B) Cellular infiltration depth of the furthest 60 cells on each image. Reproduced with permission from Minden-Birkenmaier et al., Journal of Engineered Fibers and Fabrics; published by INDA, 2015.

Figure 4

Honey increases fiber diameter. SEM images and histograms of fiber diameters of silk/PEO nanofibrous matrices spun with (a,a’) no Manukah honey; (b,b’) 10% w/v Manuka honey; (c,c’) 30% w/v Manuka honey; (d,d’) 50% w/v Manuka honey; and (e,e’) 70% w/v Manuka honey. Reproduced with permission from Yang et al., Materials & Design; published by Elsevier, 2017.

Figure 5

Honey hydrogel induces wound closure. Wound closure rates in rabbit wounds that were untreated, treated with a commercial wound ointment (MEBO), or treated with a honey-infused chitosan/gelatin hydrogel (HS) at 4, 8, or 12 days after beginning of treatment. “**” indicates statistical significance at p < 0.005, “*” indicates statistical significance at p < 0.01. Reproduced with permission from Wang et al., Carbohydrate Polymers, published by Elsevier, 2012.

Figure 6

Honey reduces inflammatory cytokine expression. mRNA expression of (a) IL-1α, (b) IL-1β, and (c) IL-6 in a rat burn wound model treated with a control hydrogel, a commercial Opsite film dressing, the honey hydrogel, or non-treated (-Ve) control, normalized to β-actin. Reproduced with permission from Zohdi et al., Evidence-based Complementary and Alternative Medicine; published by Hindawi, 2012.