Abstract
The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag+), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag+ can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics. In addition, due to the slow-release properties of Rhein hydrogel, continuous effective concentration of Ag+ at the wound site can be ensured. The assembly of Ag+ and Rhein makes the hydrogel system with enhanced mechanical stability. More importantly, it is found that Rhein effectively promotes skin tissue regeneration and wound healing by reprogramming M1 macrophages into M2 macrophages. Further mechanism studies show that Rhein realizes its powerful anti-inflammatory activity through NRF2/HO-1 activation and NF-κB inhibition. Thus, the hydrogel system combines the excellent antibacterial properties of Ag+ with the excellent anti-inflammatory and tissue regeneration ability of Rhein, providing a new strategy for wound management with dual roles.