6-Gingerol microneedle promotes diabetic wound healing by regulating macrophage polarization

Diabetic wound-healing difficulties are common for patients with diabetes. Compared to normal wound healing processes, the hyperglycaemic environment in diabetic wounds increases the proportion of M1 macrophages significantly, thereby prolonging the inflammatory phase of wound healing. Consequently, treatment approaches targeting macrophages are gaining increasing attention in both research and clinical practice. 6-Gingerol (6-G), a natural compound derived from ginger, is recognized for its anti-inflammatory, anti-tumour, and antioxidant properties. However, its application in diabetic wound treatment has been limited by poor water solubility and low bioavailability. In this study, we developed a hydrogel microneedle system (6-G@MN) combining 6-G with polyethylene glycol, hyaluronic acid, and gelatin. Our results demonstrated that 6-G@MN effectively promotes angiogenesis and collagen deposition in diabetic wounds while rebalancing macrophage populations in diabetic mice. Additionally, 6-G was shown to inhibit lipopolysaccharide-induced M1 macrophage polarization in vitro and to activate the AMPK/mTOR signalling pathway. In conclusion, we developed 6-G@MN as a novel therapeutic approach that integrates the advantages of the traditional Chinese medicine component 6-G with modern microneedle technology. By targeting macrophage polarization, the system can offer a promising strategy for improving the healing of diabetic wounds.