Cathodic voltage-controlled electrical stimulation of titanium implants as treatment for methicillin-resistant Staphylococcus aureus periprosthetic infections

Ehrensberger, Mark T.; Tobias, Menachem; Nodzo, Scott R.; Hansen, Lisa A.; Luke-Marshall, Nicole R.; Cole, Ross; Wild, Linda; Campagnari, Anthony A.

doi:10.1016/j.biomaterials.2014.11.013

Cited by 71 publications

(103 citation statements)

References 48 publications

(37 reference statements)

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“…Using a previously developed rodent MRSA IAI model [11,19], this study sought to evaluate the antimicrobial and histological effects of treatment with vancomycin alone (VANCO), one treatment of CVCES combined with vancomycin (VANCO + 1STIM), and two treatments of CVCES combined with vancomycin (VANCO + 2STIM). In addition, a group that received no treatment served as controls (CONT).…”

Section: Methodsmentioning

confidence: 99%

“…A standard procedure previously described was used to surgically place the implant [11,19]. In brief, after successful induction of anesthesia using ketamine, xylazine, and acepromazine, the ventral periaxillary area was shaved, sterilized with chlorhexidine and alcohol, and injected with local anesthetic (bupivacaine and lidocaine mix) and analgesic (buprenorphine) subcutaneously.…”

Section: Surgical Implantation and Infectionmentioning

confidence: 99%

“…Although bacterial reduction was substantial using this novel methodology, no animals were completely infectionfree at the endpoints of these previous studies [11,19]. Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with a prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels.…”

Section: Introductionmentioning

confidence: 99%

“…As a result of difficulties treating bacterial biofilms and the rise in drug-resistant bacteria, alternative therapeutic strategies must be investigated. Cathodic voltage-controlled electrical stimulation (CVCES) of titanium (Ti) implants has recently been shown to be a promising treatment against methicillin-resistant Staphylococcus aureus (MRSA) IAIs in both in vitro and in vivo studies [11,19]. We recently reported results using a rodent model of MRSA IAI showing a 99.8% reduction in the implant bacterial burden when treated with CVCES of À1.8 V versus Ag/AgCl for 1 hour in combination with a 1-week course of antibiotics [19].…”

Section: Introductionmentioning

confidence: 99%

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Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Nodzo

Tobias

Ahn

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels.Questions/purposes (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Methods Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/ kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (À1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (À1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. Results The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 9 10 4 , range = 4.0 9 10 3 À8.0 9 10 5 CFU/mL; difference of medians = À5.6 9 10 4 ; p \ 0.001) and VANCO (median = 4.9 9 10 3 , range = 9.0 9 10 2 À2.1 9 10 4 CFU/mL; difference of medians = À4.9 9 10 3 ; p \ 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 9 10 2 , range = 0-9.4 9 10 2 CFU/ mL; difference of medians = À1.3 9 10 2 ; p \ 0.001) but was not different from VANCO (median = 0, range = 0-1.3 9 10 2 CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 9 10 1 CFU/mL) and bone CFU (median = 0, range = 0-2.0 9 10 1 CFU/mL) that were not different from the VANCO + 1STIM treatment ...

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Section: Methodsmentioning

confidence: 99%

Section: Surgical Implantation and Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Nodzo

Tobias

Ahn

et al. 2016

Clinical Orthopaedics &Amp; Related Research

Self Cite

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“…Application of electric current has been shown in vitro to have a direct adverse effect on bacterial biofilms, reducing the number of viable bacteria in a time-dependent and dose-dependent manner [3]. Animal models of implant-associated infections have confirmed the action of electric current against biofilm cells [4,5]. Application of electric current exhibits a synergistic effect with antibiotic administration in vitro, which has been called the bioelectric effect [2].…”

mentioning

confidence: 99%

CORR Insights®: Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Zalavras

2016

Clinical Orthopaedics &Amp; Related Research

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Electrically Stimulated Dental Implants Triggers Soft‐Tissue Integration and Bactericidal Functions

Jayasree,

Cartmell,

Ivanovski

et al. 2024

Adv Funct Materials

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Modulating cellular functions at the dental implant‐tissue interface to augment integration and prevent bacterial ingress is crucial for achieving early stability and long‐term implant success. Nano‐engineering strategies, such as anodized titanium implants with titania (TiO2) nanotubes/nanopores, are emerging as a promising dental implant surface modification approach to enhance integration and prevent infection. Achieving on‐demand therapy through electrical stimulation therapy (EST, supply of voltage/current to local tissue) may be advantageous but has not been explored for dental implants. Further, anodized implants with TiO2 nanotubes/nanopores represent a semi‐conducting modification that can impede EST effectiveness. In this pioneering study, TiO2 nanopores are converted into conducting Ti nanopores to perform EST to achieve superior soft‐tissue integration and antibacterial efficacy. In‐depth surface characterizations are followed by assays investigating the effect of EST on cultured human salivary biofilm and gingival fibroblasts. Significant bactericidal efficacy is demonstrated for EST (1.5 V for 5 min per day) using Ti nanopores. Further, EST enhanced fibroblast proliferation and collagen secretion. In summary, EST applied to Ti nanoporous implants promotes soft‐tissue healing and antibacterial functions and is proposed as a next‐generation approach in implant dentistry to achieve on‐demand therapy.

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Cathodic voltage-controlled electrical stimulation of titanium implants as treatment for methicillin-resistant Staphylococcus aureus periprosthetic infections

Cited by 71 publications

References 48 publications

Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

CORR Insights®: Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Electrically Stimulated Dental Implants Triggers Soft‐Tissue Integration and Bactericidal Functions

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