Evaluation of Effectiveness of Honey-Based Alginate Hydrogel on Wound Healing in Rat Model

Introduction Wound healing exhibits a dynamic physiological process initiated and influenced by a lot of agents. The process can be divided into four stages: haemostasis, inflammation, proliferation, and finally remodeling [1]. Honey has long been used for treating wounds and other skin conditions [2-6], attributed to its antibacterial, anti-inflammatory, and antioxidant properties [7]. Honey is composed of sugars including mainly about 40% fructose, 30% glucose, and 10% maltose with other compounds such as oligosaccharides, minerals, carbohydrates, enzymes, and phytochemicals such as flavonoids, and ferulic and caffeic acids [8]. The specific composition depends on the flowers available to the bees that produce the honey [9, 10]. Antibacterial activity of honey is because of its high osmolarity, pH, H2O2 production, and presence of other phytochemical components that originate from the nectar of plant [11]. There are several reports on the antibacterial activities of honey against a large number of microorganisms that result in acceleration of wound healing process [11–13]. Antioxidant activity of honey arises from its phytochemical component which protects cells from the damage caused by free radicals thus decreasing the inflammation process [14]. The free radical scavenging activities of honey is mainly due to the contents of flavonoids and phenolic acids [15]. Bangroo et al., [16] have shown previously that the usage of honey can enhance the thickness of the granulation tissue and the area of re-epithelization, and Suguna et al., [17] have demonstrated that honey can enhance collagen metabolism during wound healing. Subramanian [18] exhibited that honey was superior to sulfadiazine in producing early subsidence of acute inflammatory changes, better control of infection and quicker wound healing. Several authors have reported on hydrogel technologies providing products suitable for biomedical application especially in wound management [19–21]. Hydrogels appear to be optimal media to increase wound healing due to its features including moist wound healing, good fluid absorbance as well as having high water retention capacity [19]. Thus, developing hydrogel-based wound dressings from a wide range of biomaterials as well as biologically active substances including chitin, chitosan, alginate, and sea cucumber is in the spotlight [22–25]. Various dressings and gels containing honey are now available [26, 27], but in the current study, the dressing derived from honey and alginate hydrogel was introduced as a novel dressing that have reservoir capacities for the sustained delivery of honey. The development of a sustained release system would substantially increase the utility of incorporated honey in tissue repair and thus facilitate healing and we was therefore undertaken to assess its wound-healing activity in rat model, using topically applied gel formulations. Materials and Methods Honey formulations For topical at a concentration of 70% were made. Animals A total of 20 male wistar rats (weight 180–200 g) were used in the current study. The animals were acclimatized to the laboratory conditions for one week prior to the onset of the experiment. The rats were individually caged, fed with commercial rat chow, and allowed water ad libitum. Alginate hydrogel and honey have a notably effect on wound healing process, therefore assessment of combined impact of those are essential. In this study, the effect of honey-based alginate hydrogel, alginate hydrogel and commercial alginate dressings in recovery of wound in a rat model was studied. In this study, 20Wistar rats were divided into four groups of five. One wound of 1×1 cm square was marked using a template and the skin, on either side of the vertebral column between the ears, excised. One of the rats in each group was euthanized on the 4th, 7th, 14th, and 21th days and skin samples were taken for histopathological analysis. Findings showed that the average total time of wound healing in group of treated with honey-based alginate hydrogel dressing was the best treatment as opposed to the other groups. With respect to all information obtained of the study we found that the honey-based alginate hydrogel is much convenient for wound dressing and treatment of surface wounds. Therefore, outcomes of the treatment make our dressing highly promising as an alternative wound healing system for the treatment of wounds and certainly opening new path for future research and development.