Honey, Gellan Gum, and Hyaluronic Acid as Therapeutic Approaches for Skin Regeneration.

Background/Objectives: Chronic wounds pose a significant health concern, with their prevalence increasing due to various etiologies. The global aging population further contributes to this rise, placing a substantial burden on healthcare systems in developed countries. This work aimed to develop new therapeutic options in the form of creams and dressings based on honey, gellan gum, and hyaluronic acid for preventing and treating chronic wounds across all stages. Methods: To address this, after the formulations were developed, in vitro cytocompatibility was determined. To confirm biocompatibility, an ovine wound model was used: full-thickness excisional wounds were treated with three formulations, namely gellan gum and honey sponges (GG-HNY), gellan gum, honey and hyaluronic acid sponges (GG-HA-HNY) and a honey-based cream (cream FB002). Daily assessments, including visual evaluation and wound scoring, were conducted for 30 days. Following the study period, tissues were collected for histological analyses. Results: The macroscopic examination revealed that all therapeutic groups facilitated lesion closure. Lesion size reduction, granulation tissue disappearance, and scar tissue development were consistent across all groups, with the group receiving cream demonstrating an advanced stage of healing. All groups achieved substantial wound closure by day 30, with no significant differences. Histopathological analysis following ISO standards revealed that GG-HA-HNY had the lowest ISO score, indicating minimal reactivity and inflammation, which corroborated the cytocompatibility. Conclusions: Combining these insights with previous findings enhances our understanding of wound regeneration dynamics and contributes to refining therapeutic strategies for chronic wounds. The formulations were designed to balance therapeutic efficacy with cost-effectiveness, leveraging low-cost raw materials and straightforward production methods.