à ngstrom-scale silver particle-infused hydrogels eliminate orthopedic implant infections and support fracture healing.

Orthopedic implant-associated infections pose a significant clinical challenge, often requiring surgical intervention along with systemic antibiotic treatments. To address this issue, we developed a novel approach using à ngstrom-scale silver particles (Agà Ps) with broad-spectrum antibacterial properties. Specifically, we formulated a polyethylene glycol hydrogel infused with Agà Ps (Gel-Agà Ps) designed for treating fracture fixation infections. This novel hydrogel formulation is injectable, ensuring precise adherence to both the exposed tissue and fracture surfaces, thereby allowing the direct targeted action of Agà Ps at the infection site. The Gel-Agà Ps significantly reduced the infection caused by Escherichia coli (a model pathogen of orthopedic implant infection) in a murine femoral fracture model. Moreover, the Gel-Agà Ps-treated infected fractures healed completely within 6 weeks, exhibiting bone formation and mechanical strength comparable to those of uninfected fractures. Further analysis revealed a significant downregulation of local inflammatory response as evidenced by a lower expression of inflammatory markers in Gel-Agà Ps-treated fractures compared to untreated infected controls. Furthermore, Gel-Agà Ps exhibited a unique ability to inhibit osteoclast differentiation, a critical factor in infection-induced bone degradation, without impacting osteoblast activity. In conclusion, Gel-Agà Ps exerted a dual therapeutic effect by eradicating bacterial infection and mitigating inflammation-induced osteoclast activity, thereby expediting infected fracture healing. This innovative approach is a promising therapeutic alternative to conventional antibiotic treatments, potentially transforming the treatment landscape for orthopedic implant-associated infections.