Investigation of wound healing effect of hyaluronic acid/pullulan gel formulations

The wound healing process is initiated after skin damage occurs with external factors such as physical, chemical, thermal, biological and so on. Wound healing normally occurs through well-established, overlapping steps called hemostasis, inflammation, proliferation, and remodeling. However, prolonging the healing process and progression of an acute wound to a chronic wound are undesirable situations that can negatively affect this process, and often cause the development of scar tissue. Various wound care products are available on the market to accelerate and support the wound healing process, targeting both acute and chronic wounds. Although, hydrogels stands out among these products, the requirements of cross-linking natural or synthetic polymers or synthesizing graft copolymers make the development and characterization of this systems more complex. However, gel type formulations can carry advantages of hydrogels in wound healing applications, which can easily be prepared from the physical mixtures of components. This study aimed to develop non-crosslinked gel formulations based on binary physical mixtures of hyaluronic acid and pullulan. A Design of Experiments (DOE) matrix was carried out to reach optimum gel formulations, by using the results obtained by Texture Profile Analysis. After optimizing the gel formulations, the differential scanning calorimetry and rheological studies were performed. After characterizations studies, 4 formulations containing 2% hyaluronic acid and pullulan with various concentrations at 0, 2, 5, and 8% (F1, F2, F3, and F4, respectively) were examined in circular excision wound model in mice. F3 and F4 exhibited more pronunced effect on the investigated wound model compared to the other groups according to the wound area measurements and histopathological study. These results were attributed mainly to the potential wound healing effect of pullulan, and partly to the structural regulatory role and space filling effect hyaluronic acid. This study clearly demonstrate the possible use of pullulan based gels as wound-healing agents.