Staged Low-Frequency Ultrasound Synergized with Composite Hydrogel to Achieve "Rapid Antimicrobial-Ordered Regeneration" of Infected Wounds.

Abstract

Bacterial-infectious wounds present a significant threat to global health due to an altered microenvironment that promotes drug-resistant bacterial persistence. Given the limitations of traditional dressings, static drug release mechanisms, and singular antibacterial action, along with the issue of drug resistance exacerbated by the overuse of antibiotics, a dual dynamic cross-linked network composite hydrogel (CSGA-Cip) is developed to overcome these challenges. The hydrogel forms a dynamic adaptive network through Schiff base bonds and Ag─S coordination bonds, endowing it with injectable and self-healing properties. Notably, a staged low-frequency ultrasound intervention strategy is employed to achieve a cascade treatment of antibacterial ordered regeneration. During acute infection (0-3 days), continuous low-frequency ultrasound facilitates the rapid release of silver ions (Ag⁺) and ciprofloxacin (Cip), synergizing with glutathione (GSH) to establish multiple antibacterial barriers. In the repair stage (3-9 days), pulsed low-frequency ultrasound activated cell migration and angiogenesis signaling pathways to guide tissue regeneration. Animal studies have confirmed that this strategy significantly enhances infectious wound healing, promotes orderly collagen deposition, and stimulates angiogenesis, thereby providing an innovative paradigm for the treatment of infectious wounds.