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&...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 usingÅngstrom-scale silver particles(AgAPs)with broad-spectrum antibacterial properties.Specifically,we formulated a polyethylene glycol hydrogel infused with AgAPs(Gel-AgAPs)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 AgAPs at the infection site.The Gel-AgAPs significantly reduced the infection caused by Escherichia coli(a model pathogen of orthopedic implant infection)in a murine femoral fracture model.Moreover,the Gel-AgAPs-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-AgAPs-treated fractures compared to untreated infected controls.Furthermore,Gel-AgAPs exhibited a unique ability to inhibit osteoclast differentiation,a critical factor in infection-induced bone degradation,without impacting osteoblast activity.In conclusion,Gel-AgAPs 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.展开更多
基金supported by the National Natural Science Foundation of China(Grant no.:82125023 and 82072504 to HX and grant no.:82272562 to ZW)the Science and Technology Innovation Program of Hunan Province(Grant no.:2023RC3075 to ZW)the Hunan Province Natural Science Foundation of China(Grant no.:2023JJ20096 to ZW and grant no.:2023JJ30872 to WD).
文摘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 usingÅngstrom-scale silver particles(AgAPs)with broad-spectrum antibacterial properties.Specifically,we formulated a polyethylene glycol hydrogel infused with AgAPs(Gel-AgAPs)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 AgAPs at the infection site.The Gel-AgAPs significantly reduced the infection caused by Escherichia coli(a model pathogen of orthopedic implant infection)in a murine femoral fracture model.Moreover,the Gel-AgAPs-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-AgAPs-treated fractures compared to untreated infected controls.Furthermore,Gel-AgAPs exhibited a unique ability to inhibit osteoclast differentiation,a critical factor in infection-induced bone degradation,without impacting osteoblast activity.In conclusion,Gel-AgAPs 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.
