The ROS-responsive FA@Ni@HA hydrogel promotes infected wound healing in DIO mice through endogenous antimicrobial peptides and macrophage recruitment

In infected wounds, adipocytes play a crucial role in resisting infection. Studies have demonstrated that a lack of adipocytes can reduce the recruitment of macrophages. When wounds are infected, dermal fibroblasts (dFBs) differentiate into adipocytes and produce antimicrobial peptides (AMPs) to combat bacteria. However, in obesity mice, mature adipocytes hinder the adipogenic differentiation of dFBs and the production of AMPs. It is unclear whether promoting lipolysis can restore the function of AMPs secretion. Nickel ion (Ni2+) is known for promoting vascular regeneration and has been widely used in tissue regeneration. Therefore, the ROS-responsive ferulic acid (FA)@Ni@HA hydrogel was developed to promote infected wound healing. FA released from the hydrogel can promote the lipolysis of adipocytes to alleviate the inhibition of mature adipocytes on AMPs secretion from dFBs and enhance macrophage recruitment. Additionally, the loaded Ni2+ can stimulate local blood vessel formation, working in conjunction with FA to promote the healing of infected wounds. The results suggest that the use of FA@Ni@HA hydrogel expedites the repair of infected wounds, offering a promising strategy for wound healing.