Related Experiment Video
Updated: Dec 4, 2025
Animal Model of Implant-Associated Infections in Mice
Published on: June 27, 2025
Antibacterial effect of a copper-containing titanium alloy against implant-associated infection induced by
Yifu Zhuang1, Ling Ren2, Shuyuan Zhang2
1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Implant-associated infection (IAI) induced by methicillin-resistant Staphylococcus aureus (MRSA) is a devastating complication in the orthopedic clinic. Traditional implant materials, such as Ti6Al4V, are vulnerable to microbial infection. In this study, we fabricated a copper (Cu)-containing titanium alloy (Ti6Al4V-Cu) for the prevention and treatment of MRSA-induced IAI. The material characteristics, antibacterial activity, and biocompatibility of Ti6Al4V-Cu were systematically investigated and compared with those of Ti6Al4V. Ti6Al4V-Cu provided stable and continuous Cu2+ release, at a rate of 0.106 mg/cm2/d. Its antibacterial performance against MRSA in vitro was confirmed by plate counting analysis, crystal violet staining, and scanning electron microscopic observations. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that Ti6Al4V-Cu suppressed biofilm formation, virulence, and antibiotic-resistance of MRSA. The in vivo anti-MRSA effect was investigated in a rat IAI model. Implants were contaminated with MRSA solution, implanted into the femur, and left for 6 weeks. Severe IAI developed in the Ti6Al4V group, with increased radiological score (9.6 ± 1.3) and high histological score (10.1 ± 1.9). However, no sign of infection was found in the Ti6Al4V-Cu group, as indicated by decreased radiological score (1.3 ± 0.4) and low histological score (2.3 ± 0.5). In addition, Ti6Al4V-Cu had favorable biocompatibility both in vitro and in vivo. In summary, Ti6Al4V-Cu is a promising implant material to protect against MRSA-induced IAI.
Insights
A novel copper-containing titanium alloy (Ti6Al4V-Cu) effectively prevents and treats methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infections. This advanced material shows excellent antibacterial activity and biocompatibility, offering a promising solution for orthopedic implants.
Area of Science:
- Biomaterials Science
- Orthopedic Surgery
- Infectious Diseases
Background:
- Implant-associated infections (IAI) caused by methicillin-resistant Staphylococcus aureus (MRSA) are a significant clinical challenge.
- Conventional titanium alloys like Ti6Al4V are susceptible to microbial colonization and infection.
- Effective strategies are needed to prevent and treat MRSA-induced IAI in orthopedic procedures.
Purpose of the Study:
- To develop and evaluate a novel copper (Cu)-containing titanium alloy (Ti6Al4V-Cu) for preventing and treating MRSA-induced IAI.
- To assess the material characteristics, antibacterial efficacy, and biocompatibility of Ti6Al4V-Cu compared to Ti6Al4V.
- To investigate the in vitro and in vivo performance of Ti6Al4V-Cu against MRSA.
Main Methods:
- Fabrication of Ti6Al4V-Cu alloy and characterization of its properties, including Cu2+ release rate.
- In vitro assessment of antibacterial activity against MRSA using plate counting, crystal violet staining, and scanning electron microscopy.
- Evaluation of MRSA biofilm formation, virulence, and antibiotic resistance using RT-qPCR.
- In vivo study using a rat femur IAI model, assessing radiological and histological scores after 6 weeks.
Main Results:
- Ti6Al4V-Cu demonstrated stable and continuous Cu2+ release (0.106 mg/cm2/d).
- Significant in vitro antibacterial activity against MRSA, inhibiting biofilm formation, virulence, and antibiotic resistance.
- In vivo, Ti6Al4V-Cu implants showed no signs of infection (radiological score 1.3 ± 0.4, histological score 2.3 ± 0.5).
- Ti6Al4V implants in the control group developed severe IAI (radiological score 9.6 ± 1.3, histological score 10.1 ± 1.9).
- Ti6Al4V-Cu exhibited favorable biocompatibility in both in vitro and in vivo evaluations.
Conclusions:
- Ti6Al4V-Cu alloy possesses potent antibacterial properties against MRSA.
- The material effectively prevents and treats MRSA-induced implant-associated infections in a preclinical model.
- Ti6Al4V-Cu represents a promising biomaterial for orthopedic implants to combat MRSA infections.
