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RESEARCH ARTICLE
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Ångstrom-scale silver particle-infused hydrogels eliminate orthopedic implant infections and support fracture healing

Wei Du1,2,3,4# Jiang-Shan Gong1,2# Xia Chen1,2,4,5 Yang Wu1,2 Yu Yang1,2 Sheng Zhu1,2,4 Yu Zhang1 Bei Chen1 Yi-Wei Liu1,2 Ze-Hui He1,2 Zhe Guan1,2 Yan Zhang2,6* Zhen-Xing Wang1,2,4* Hui Xie1,2,4*
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1 Department of Orthopaedics, Movement System Injury and Repair Research Centre, Xiangya Hospital, Central South University, Changsha, Hunan, China
2 Hunan Key Laboratory of Angmedicine, Changsha, Hunan, China
3 Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, Hunan, China
4 National Clinical Research Centre for Geriatric Disorders (Xiangya Hospital), Changsha, Hunan, China
5 Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, China
6 State Key Laboratory of Powder Metallurgy Central South University, Changsha, Hunan, China
Submitted: 8 December 2024 | Revised: 15 January 2025 | Accepted: 28 February 2025 | Published: 25 March 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Abstract

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 Ångstrom-scale silver particles (AgÅPs) with broad-spectrum antibacterial properties. Specifically, we formulated a polyethylene glycol hydrogel infused with AgÅPs (Gel-AgÅPs) 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 AgÅPs at the infection site. The Gel-AgÅPs significantly reduced the infection caused by Escherichia coli (a model pathogen of orthopedic implant infection) in a murine femoral fracture model. Moreover, the Gel-AgÅPs-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-AgÅPs-treated fractures compared to untreated infected controls. Furthermore, Gel-AgÅPs exhibited a unique ability to inhibit osteoclast differentiation, a critical factor in infection-induced bone degradation, without impacting osteoblast activity. In conclusion, Gel-AgÅPs 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.

Keywords
Ångstrom-scale silver particles
antibacterial
fracture healing
orthopedic implant infections
polyethylene glycol hydrogel
Funding
This work was 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), and the Hunan Province Natural Science Foundation of China (Grant no.: 2023JJ20096 to ZW and grant no.: 2023JJ30872 to WD).
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Conflict of interest
The authors declare no conflicts of interest.
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