Honey is used in wound dressing for diabetic ulcer treatment because it has various features such as antibacterial, anti-inflammatory, antioxidant, and autolytic debridement.

One of the diabetes mellitus complications is the problem of wounds, namely ulceration, infection, and gangrene. A diabetic ulcer is the most common cause of hospitalization in diabetic patients. The principles of diabetic ulcer treatment are debridement, decreasing the burden, and controlling the infection. One part of the debridement process is wound treatment by wound dressing.

Amputation rates that are not related to trauma in diabetes are 50-70%, and most are due to diabetic ulcers. Treatment of diabetic ulcers, education of patients and their families, and comprehensive control are expected to reduce amputation rates.

Some topical regimens used as wound dressing are wet-to-dry dressing (using regular clean gauze and saline liquid), topical antibiotics (example: metronidazole gel), tulle dressing, polyurethane coating, hydrogel dressing, hydrocolloid dressing, alginate dressing, honey-containing dressing, topical enzymes, and mechanical equipment.

Honey is considered a primary wound dressing in:

1. Dry necrotic wound. Honey functions to remove non-viable tissue.
2. Wounds that have a slough, brownish-yellow to black, and have a low exudate to dry.

These recommendations must be readjusted with clinical decisions and local protocols that apply.

Features found in honey related to healing diabetic ulcers include:

a. Acidity (pH 3.2 - 4.5).
Honey can prevent the formation of biofilm layers and together with the sugar content, can help macrophages to kill germs. Besides, the honey acidity creates environmental conditions that increase the release of oxygen from hemoglobin. It will stimulate wound healing through the granulation process and can reduce protease activity for increased fibroblast activity.

b. Osmotic effect.
Honey is hyperosmolar who creates an environment that is not conducive for germs to grow. The liquid will be attracted to the wound area and can then form a protective layer against cross-contamination. Lymph fluid can also be drawn and stimulate autolytic debridement. It should be noted if honey is mixed with exudates from the wound, it will reduce the effects of hyperosmolar.

c. Hydrogen peroxide (H2O2)
Hydrogen Peroxide is a result of the glucose oxidase enzyme activity. In low concentrations, it can stimulate fibroblasts, epithelial cells, angiogenesis in vivo. Hydrogen peroxide with neutrophils together can kill bacteria. 

d. Nitric oxide (NO)
NO is needed during the proliferative stage of the wound healing process. In addition, the final product from NO also has the potential to help wound healing.

Antibacterial Activity

The antibacterial activity of honey has a broad spectrum against gram-positive, gram-negative, aerobic and anaerobic bacteria, but is less effective against fungi. Also, some experts say honey is effective against bacteria that have antibiotic resistance such as MRSA (Methicillin-resistant Staphylococcus aureus), VRE (Vancomycin-resistant Enterococci), pseudomonas, Acinetobacter baumanii, and Stenotrophomonas maltophilia. The provision of honey in high concentrations by clinical indications can avoid bacterial resistance to the antibacterial effect of honey.

Biofilm Inhibiting Activity

Biofilms can be found in many chronic wounds and make wound healing difficult. Honey active substances can penetrate the biofilm matrix that has been formed. Also, honey can kill bacteria that have the potential to form biofilms.

Debridement Activity

In chronic infections, there is an increase in proteases. It will reduce levels of growth factors and extracellular matrix components that inhibit the wound healing process. Protease requires alkaline conditions to work optimally. As mentioned before, honey can reduce the activity of proteases because it has a low pH feature. The osmotic effect of honey can also attract lymph fluid to the injured area and make it damp. Therefore it can stimulate autolytic debridement.

Anti-inflammatory and Antioxidant effects

The anti-inflammatory effect on honey is probably caused by the inactivation of reactive oxygen species (ROS) and the sugar contained in honey provides macrophages as fuel to produce H2O2 and energy. Plant phenolics in honey also have antioxidant effects that can remove free radicals. These processes can cut the chronic inflammatory cycle.

Selection of Honey for Diabetic Ulcers

The selection an effective honey types for diabetic ulcers is a challenge because of the difference in the composition of each honey. There are commercial wound dressing products that contain honey, but their effects may vary from manufacturer to producer. Types of honey that have been proven to provide benefits for diabetic ulcers include:

a. Manuka honey is pure monofloral honey from bees in manuka plants (Leptospermum scoparium) are widely found in Australia and New Zealand.
In a study (n = 63) comparing wound dressing using manuka honey with conventional dressing (moist gauze with normal saline), the recovery time was faster in the honey group (31 ± 4 days versus 43 ± 3 days, p <0.05). The combination of using the manuka honey method and the conventional method reduced the number of toe amputations (due to complications) compared to the conventional method alone (9.7% versus 34.6%; p <0.05).

b. In a study in Malaysia, they compared unsterile honey ( which is sold commercially for food), with iodine povidone and normal saline (as control) in Wagener-II diabetic foot sores. They found the healing time in the honey group was 14.4 days (7-26 days), and the control group was 15.4 days (9-36 days). This difference was not statistically significant, but in the honey group, other benefits were found, namely decreased edema and odor in wounds.

The frequency of dressing the wound with honey is once a day in 9 of 11 studies that stated the success of the management of diabetic ulcers. Bandages can be changed more often if there are many exudates and can be done less often if the number of drainage decreases (4 - 7 days). In hard wounds, it can be done with honey compress melted with normal saline in a ratio of 1: 3.

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