Investigation of minocycline and hyaluronic acid combined with ultrasound therapy in a Staphylococcus aureus-infected rat wound model

This study aimed to examine the effects of minocycline (MINO) and hyaluronic acid (HA) on wound healing in rats. MINO/HA was combined with ultrasound therapy for treating wounds infected with <i>Staphylococcus aureus</i>. Cutaneous wounds in 40 female Wistar rats were infected with <i>S. aureus</i> and then randomly divided into four groups: infected-wounded skin treated with sterile saline solution (control group), treated with ultrasound (ultrasound group), treated by a mixture of MINO and HA (MINO+HA group) and treated with a mixture of MINO and HA combined with ultrasound (MINO+HA+ultrasound group). General observations of the wound healing were photographed. After three treatments, bacterial counts were obtained to determine antibacterial efficacy and wound healing was assessed by histological analysis and evaluation of inflammatory cytokine levels (TNF-<i>α</i> and IL-1<i>β</i>) by immunohistochemistry. Compared with the control group, both the MINO+HA group and the MINO+HA+ultrasound group achieved a significant wound square reduction of 43.7% and 54.9 %, respectively (<i>P</i><0.001). A small number of inflammatory cells, organization of collagen fibres and maturation of granulation tissue were observed in the histological evaluation of the MINO+HA+ultrasound group. The expression levels of TNF-<i>α</i> and IL-1<i>β</i> in the MINO+HA+ultrasound group were decreased compared to both the control group and the MINO+HA group (<i>P</i><0.001). These findings revealed the possibility of using a mixture of MINO and HA combined with ultrasound to minimize inflammation and promote tissue regeneration during the treatment of wound infections.