Introduction
Using honey to facilitate wound healing in surgical dressings dates back to years ago [1]. A wide variety of microorganisms may colonize the burn wound and initiate a systemic infection [2]. Unlike antibiotics, honey has properties that make it difficult for bacteria to change and adapt to honey; hence, bacteria do not become resistant to honey [3]. Stimulation of the inflammatory response by honey administration causes the production of growth factors responsible for angiogenesis and fibroblast proliferation, which accelerates the wound healing [4]. Honey also reduces scar and tissue contracture [5]. Honey is antioxidant and bacteriostatic effects. It has anti-inflammatory properties and can debride the wound [6]. One of the methods of fixing the skin graft is the use of a stapler, but this method increases the risk of hematoma, and patients experience more pain. Stapler is more expensive than honey and increases the days of hospitalization and puts a financial burden on the patient [7]. This study aims to compare the effects of using medical honey and staplers for skin graft fixation in patients with burn wounds in the north of Iran.

Methods
In this non-blinded randomized clinical trial, the study population consisted of all patients with deep second- and third-degree burns who needed a skin graft and burned less than 40% of total body surface area, whose graft was performed in a single stage and hospitalized in a hospital for burn injuries in Rasht, Iran. Patients were divided into two groups of honey and stapler. The exclusion criteria were the patient’s death and lack of access to the patient for any reason. Demographic information was extracted from patients’ medical records. For all patients, the variables of graft rejection, displacement of grafted skin, graft contracture, number of hospitalization days after the grafting, edema, hematoma, itching, pain, and infection after grafting were investigated and recorded. A minimum sample size of 40 was determined for each group, 80 in total. The block randomization method was used for allocation of patients. All patients received routine and standard burn treatments, and if antibiotics were needed, the same antibiotic was used in both groups. In the first group, honey was used to attach the skin graft to the underlying tissue. The primary outcome was the effectiveness of honey and stapler in fixating the skin graft, through observation, according to the burn expert’s opinion. The secondary outcomes were displacement of grafted skin and graft contracture, confirmed infection, hematoma, edema, rejection of graft based on the color change, photography, and expert’s opinions; pain level using the visual analogue scale, the degree of itching using the 5D pruritus scale, and length of hospitalization after grafting.

Results
Of 80 patients, 34(42.5%) were male. The mean age of the patients was 39.29±15.42 years in total, 40.60±18.86 years in the honey group, and 37.98±11.05 years in the stapler group. This difference between the two groups was not statistically significant (P=0.450). The mean burn percentage was 33.38%±10.70 in the honey group and 35.08%±9.14 in the stapler group; this difference was insignificant (P=0.447). There was no graft rejection in any groups, and skin grafting was successful in both groups. The mean number of hospitalization days after grafting was 8.5±1.89 days in the honey group and 11.23±4.79 days in the stapler group, which was significantly different (P=0.034). The mean displacement of grafted skin was 6.35±3.24 mm in the honey group and 5.6±2.37 mm in the stapler group, but the difference was not significant (P=0.242). The mean amount of graft contracture was 3.95±2.33 mm in the honey group and 2.98±1.57 mm in the stapler group, where the amount of contracture in stapler group was significantly lower (P=0.031). The results of comparing the mean pain intensity between the two groups in different time points showed that the mean pain intensity was lower in the honey group at all time points. Also, the mean severity of itching in the honey group was lower than in the stapler group at all time points. The percentage of infection, edema, and hematoma were lower in the honey group.

Conclusion 
The results obtained in this research indicate that the use of medicinal honey in the treatment of burn wounds has been able to reduce adverse effects such as pain, itching, edema, hematoma and infection. In addition, the results show that the patients with burn wounds who were treated with the medical honey method were discharged from the hospital and recovered faster than the patients who were treated with the stapler method. Skin shrinkage was more in the method of using honey, and to solve this problem, you can use the method of overlapping the graft with the surrounding skin. Also, the use of medical honey to connect the graft to the underlying tissue was efficient as a routine treatment. In general, it can be stated that the use of treatment based on medical honey can improve the complications of burn wounds treatment in patients, and besides being more affordable and safer, it also reduces the duration of treatment.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Research Ethics Committee of Guilan University of Medical Sciences (Code: IR.GUMS.REC.1400.304), and registered at Iranian Registry of Clinical Trials (IRCT) (Code: IRCT20210524051384N2). All patients received routine treatment. Their information was kept confidential. Informed consent was obtained from them; they were free to leave the study at any time and If needed, the results of the study would be available to them.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions
Conceptualization, study design, financial resources, administration and supervision: Nematollah Ahangar and Mohammadreza Mobayen; Data acquisition, analysis and interpretation of data: Nematollah Ahangar, Mohammadreza Mobayen, Alale Jarrahi, Mohammad Ebrahim Ghaffari and Mojdeh Esmailzadeh; Statistical analysis: Mohammad Ebrahim Ghaffari and Mojdeh Esmailzadeh. Writing the original draft: Nematollah Ahangar, Parissa Bagheri Toolaroud and Amirhossein Pourebrahimi; Critical review of the manuscript for important intellectual content: Nematollah Ahangar and Mohammadreza Mobayen, Amirhossein Pourebrahimi, Mohammad Ebrahim Ghaffari and Parissa Bagheri Toolaroud.

Conflicts of interest
The author declared no conflict of interest.


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