In Vivo Efficacy of a “Smart” Antimicrobial Implant Coating

Stavrakis, Alexandra I.; Zhu, Shaobo; Hegde, Vishal; Loftin, Amanda H.; Ashbaugh, Alyssa G.; Niska, Jared A.; Miller, Lloyd S.; Segura, Tatiana; Bernthal, Nicholas M.

doi:10.2106/jbjs.15.01273

Cited by 47 publications

(63 citation statements)

References 49 publications

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“…e synthesis of the PEG-PPS polymer was the same as previously described [19]. An orthopaedic-grade titanium Kirschner-wire (K-wire) (diameter 0.6 mm) underwent oxygen plasma treatment at 200 mTorr and 200 W for 15 min.…”

Section: Synthesis Of Peg-pps Block Copolymer Antibioticmentioning

confidence: 99%

“…Our objective in this study was to develop a bioabsorbable implant coating to deliver antibiotics locally via an intramedullary implant. Additionally, the polymer coating was designed to confer several specific unique benefits: (1) the coating polymerizes rapidly in a nonexothermic reaction, allowing incorporation of heat sensitive antibiotics and antimicrobials, (2) the coating can release antibiotics over a sustained period of time, and (3) the coating is completely biodegradable and has been demonstrated to not have a negative effect on osseointegration [19]. A mouse model of postarthroplasty infection using a bioluminescent strain of Staphylococcus aureus (S. aureus) has previously been established [20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model

Stavrakis

Zhu

Loftin

et al. 2019

BioMed Research International

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Introduction.Treatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes. Methods. In this study, a novel open fracture mouse model was developed using Staphylococcus aureus (S. aureus) and single-stage intramedullary fixation. e model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus. In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period. Results. We found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray. Conclusion. Vancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. is novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans.

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Section: Synthesis Of Peg-pps Block Copolymer Antibioticmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model

Stavrakis

Zhu

Loftin

et al. 2019

BioMed Research International

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“…Similarly, Stavrakis et al used in vivo BLI in the K‐wire mouse model of OIAI with an implant coating composed of poly(ethylene glycol)‐poly(propylene sulfide) that released either vancomycin or tigecycline. They reported that the local release from the coating of tigecycline was more effective than vancomycin in reducing the bacterial burden . In addition, they also used in vivo FLI with a near‐infrared dye incorporated into the coating to estimate the in vivo antibiotic release duration from the coating .…”

Section: Treatmentmentioning

confidence: 99%

“…47 Of note, the coating with combinatorial linezolid and rifampin release also prevented an MRSA (SAP231) infection in our rabbit model of OIAI. 35 Similarly, Stavrakis et al 48 used in vivo BLI in the K-wire mouse model of OIAI with an implant coating composed of poly(ethylene glycol)-poly(propylene sulfide) that released either vancomycin or tigecycline. They reported that the local release from the coating of tigecycline was more effective than vancomycin in reducing the bacterial burden.…”

Section: Pathogenesismentioning

confidence: 99%

“…48 In addition, they also used in vivo FLI with a near-infrared dye incorporated into the coating to estimate the in vivo antibiotic release duration from the coating. 48 Finally, Inzana et al 31 in a revision surgery OIAI model utilized in vivo BLI to determine that vancomycin-eluting cement had no additional therapeutic benefit compared with parenteral vancomycin administration. This study is particularly relevant because antibiotic-loaded bone cement is routinely used in the clinical practice of orthopaedic surgery.…”

Section: Pathogenesismentioning

confidence: 99%

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Preclinical Optical Imaging to Study Pathogenesis, Novel Therapeutics and Diagnostics Against Orthopaedic Infection

Thompson

Miller

2019

Journal Orthopaedic Research

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Preclinical in vivo optical imaging includes bioluminescence imaging (BLI) and fluorescence imaging (FLI), which provide noninvasive and longitudinal monitoring of biological processes in an in vivo context. In vivo BLI involves the detection of photons of light from bioluminescent bacteria engineered to naturally emit light in preclinical animal models of infection. Meanwhile, in vivo FLI involves the detection of photons of a longer emission wavelength of light after exposure of a fluorophore to a shorter excitation wavelength of light. In vivo FLI has been used in preclinical animal models to detect fluorescent‐labeled host proteins or cells (often in engineered fluorescent reporter mice) to understand host‐related processes, or to detect injectable near‐infrared fluorescent probes as a novel approach for diagnosing infection. This review describes the use of in vivo optical imaging in preclinical models of orthopaedic implant‐associated infection (OIAI), including (i) pathogenesis of the infectious course, (ii) monitoring efficacy of antimicrobial prophylaxis and therapy and (iii) evaluating novel near‐infrared fluorescent probes for diagnosing infection. Finally, we describe optoacoustic imaging and fluorescence image‐guided surgery, which are recent technologies that have the potential to translate to diagnosing and treating OIAI in humans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2269–2277, 2019

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Bioactive Glass‐Based Coatings: Concepts for Improving the Biocompatibility of Implantable Materials

Fletcher¹,

Alles²,

Keenan³

et al. 2022

Bioactive Glasses and Glass‐Ceramics

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In Vivo Efficacy of a “Smart” Antimicrobial Implant Coating

Abstract: PEG-PPS polymer provides a controlled, "smart" local delivery of antibiotics that could be used to prevent postoperative implant-related infections.

Cited by 47 publications

References 49 publications

Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model

Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model

Preclinical Optical Imaging to Study Pathogenesis, Novel Therapeutics and Diagnostics Against Orthopaedic Infection

Bioactive Glass‐Based Coatings: Concepts for Improving the Biocompatibility of Implantable Materials

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