Silver carboxylate-TiO2/polydimethyl siloxane is a safe and effective antimicrobial with significant wound care potential.

Introduction: With the rise in antibiotic resistance, new methodologies are needed to combat musculoskeletal infections. Silver is an antimicrobial that can be synthesized in different forms, but its pharmacokinetics are difficult to control. This study details the antibacterial efficacy and cellular cytotoxicity of a formulation consisting of silver carboxylate (AgCar) released through a titanium dioxide/polydimethylsiloxane matrix with a predictable release profile on Pseudomonas aeruginosa, Acinetobacterium baumannii, and human-derived primary osteoblasts. Methods: Through an Institutional Animal Care and Use Committee and IRB-approved protocol, AgCar was applied to live Yucatan porcine skin and histologically analyzed for skin penetration. Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) was used to measure elution of AgCar. Dose-response curves were generated through optical density to assess potency. Finally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to quantify the cellular cytotoxicity of the novel formulation. The results were subject to statistical analysis using analysis of variance and post hoc Tukey tests. Results: The silver carboxylate coating demonstrated deep penetration into the epithelium at the level of the deep pilosebaceous glands in animal models. GFAAS testing demonstrated the extended elution profile of silver carboxylate over 96 hours, while 100% silver with no titanium dioxide-polydimethylsiloxane matrix fully eluted within 48 hours. 10x silver carboxylate demonstrated superior antimicrobial activity to antibiotics and other silver formulations and showed minimal cytotoxicity compared with other silver formulations. Discussion/Clinical Relevance: Current antimicrobial therapies in wound care and surgical antisepsis, such as chlorhexidine gluconate, have pitfalls including poor skin penetration and short duration of efficacy. The broad antimicrobial activity, extended elution, and deep skin penetration of this AgCar formulation show great promise for surgical site infection and wound care treatment. Novel technology to fight the growing threat of microbial resistance should be at the forefront of orthopaedic surgical site infection prevention and treatment.

Mechanically stable rifampin antibiotic cement inhibits Pseudomonas aeruginosa biofilm surface growth.

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. The null hypothesis tests if rifampin use in polymethyl methacrylate (PMMA) cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0, 30, 50, 100, 150, or 200 mg of rifampin into a standard 40 g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipopolysaccharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30 and 50 mg, showed no statistically different mechanical characteristics from control PMMA (p > 0.05). The 100-mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to the control at 12 and 24 h. The ability of PMMA with 100 mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 h makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100 mg of rifampin shows promise in the treatment and prevention of periprosthetic joint infection for total knee and total hip arthroplasty.

Comparison of periprosthetic joint infection rates in the direct anterior approach and non-anterior approaches to primary total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Periprosthetic joint infection is a serious complication and devastating mode of failure of total hip arthroplasty. Various surgical approaches exist for total hip arthroplasty, including the increasingly popularised direct anterior approach. There is no clear consensus on which approach is least associated with periprosthetic joint infection. The objective of this meta-analysis was to compare the rate of periprosthetic joint infection between surgical approaches to primary total hip arthroplasty for osteoarthritis. METHODS: A search of 3 electronic databases (PubMed/MEDLINE, Embase, and Cochrane Library) was conducted for relevant studies up to June 2020 with a defined list of inclusion and exclusion criteria. Randomised controlled trials and longitudinal studies reporting periprosthetic joint infection rates after primary total hip arthroplasty for osteoarthritis were included based on surgical approach. Data extraction was completed, and a meta-analysis was then performed using OpenMeta[Analyst] software. RESULTS: A total of 24,407 hips were included for meta-analysis with an overall PJI incidence of 0.57%. The incidence rate for periprosthetic joint infection was 0.77% in the direct anterior approach group and 0.44% in the non-anterior approach group. The use of an anterior approach for a total hip arthroplasty was associated with an increased risk for periprosthetic joint infection (odds ratio = 1.404; 95% confidence interval, 0.711-2.771; p = 0.03). CONCLUSIONS: The direct anterior approach to total hip arthroplasty may be associated with a significantly increased risk for periprosthetic joint infection compared to non-anterior approaches, even though the overall rate was still small. This should be considered by orthopedic surgeons when choosing the surgical approach.

Silver Carboxylate-Eluting Titanium-Dioxide Polydimethylsiloxane Coating Inhibits Multi-Drug-Resistant Acinetobacterium baumannii and Vancomycin-Resistant Enterococcus faecalis Adherence and Proliferation on Orthopedic Trauma Fixation and Spinal Fusion Materials.

Background: Vancomycin-resistant Enterococcus faecalis and multi-drug-resistant (MDR) Acinetobacter baumannii are rising contributors to spinal fusion and fracture-associated infections (FAI), respectively. These MDR bacteria can form protective biofilms, complicating traditional antibiotic treatment. This study explores the effects of the antibiotic-independent antimicrobial silver carboxylate (AgCar)-doped coating on the adherence sand proliferation of these pathogens on orthopedic implant materials utilized in spinal fusion and orthopedic trauma fixation. Methods: Multi-drug-resistant Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis were inoculated on five common implant materials: cobalt chromium, titanium, titanium alloy, polyether ether ketone, and stainless steel. Dose response curves were generated to assess antimicrobial potency. Scanning electron microscopy and confocal laser scanning microscopy were utilized to characterize and quantify growth and adherence on each material. Results: The optimal AgCar concentration was a 95% titanium dioxide (TiO2)-5% polydimethylsiloxane (PDMS) matrix combined with 10 × silver carboxylate, which inhibited bacterial proliferation by 89.40% (p = 0.001) for MDR Acinetobacter baumannii and 84.02% (p = 0.001) for vancomycin-resistant Enterococcus faecalis compared with uncoated implants. A 95% TiO2-5% PDMS matrix combined with 10 × AgCar was equally effective at inhibiting bacterial proliferation across all implant materials for MDR Acinetobacter baumannii (p = 0.19) and vancomycin-resistant Enterococcus faecalis (p = 0.07). A 95% TiO2-5% PDMS matrix with 10 × AgCar is effective at decreasing bacterial adherence of both MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis on implant materials. Conclusions: Application of this antibiotic-independent coating for surgery in which these implant materials might be used may prevent adherence, biofilm formation, spinal infections, and FAI by MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis.

Silver as an Antibiotic-Independent Antimicrobial: Review of Current Formulations and Clinical Relevance.

Background: The increase of multi-drug-resistant organisms has revived the use of silver as an alternative antibiotic-independent antimicrobial. Although silver's multimodal mechanism of action provides low risk for bacterial resistance, high local and uncontrolled concentrations have shown toxicity. This has resulted in efforts to develop novel silver formulations that are safer and more predictable in their application. Optimization of silver as an antimicrobial is crucial given the growing resistance profile against antibiotics. This article reviews formulations of silver used as antimicrobials, focusing on the mechanisms of action, potential for toxicity, and clinical applications. Methods: A search of four electronic databases (PubMed, Embase, MEDLINE, and Cochrane Library) was conducted for relevant studies up to January 2022. Searches were conducted for the following types of silver: ionic, nanoparticles, colloidal, silver nitrate, silver sulfadiazine, silver oxide, silver carboxylate, and AQUACEL® (ConvaTec, Berkshire, UK). Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. Results: A review of the antimicrobial activity and uses of ionic silver, silver nanoparticles, colloidal silver, silver nitrate, silver sulfadiazine, silver oxide, Aquacel, and silver carboxylate was conducted. The mechanisms of action, clinical uses, and potential for toxicity were studied, and general trends between earlier and more advanced formulations noted. Conclusions: Early forms of silver have more limited utility because of their uncontrolled release of silver ions and potential for systemic toxicity. Multiple new formulations show promise; however, there is a need for more prospective in vivo studies to validate the clinical potential of these formulations.

Synergistic Effects of Silver Carboxylate and Chlorhexidine Gluconate for Wound Care and Prevention of Surgical Site Infections by Cutibacterium acnes and Methicillin-Resistant Staphylococcus aureus.

Background: This study presents the effectiveness of a combined silver carboxylate (AgCar) and chlorohexidine gluconate (AgCar:CHG) chemistry assessed against two commonly encountered nosocomial pathogens, Methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes, within the context of surgical antisepsis and wound care. Methods: Through an Institutional Review Board- and Institutional Animal Care and Use Committee (IACUC)-approved protocol, AgCar:CHG was applied to live Yucatan porcine skin and visualized by fast red and green staining to assess level of skin penetration. Dose response curves for Cutibacterium acnes and MRSA were generated to determine the optimal therapeutic ratio of AgCar to CHG. Coatings were applied to two different clinically available sutures and antimicrobial efficacy was evaluated at 24-hour intervals using Kirby-Bauer (KB) assays. Graphite furnace atomic absorption spectroscopy was used to measure AgCar elution from sutures over time. Results: Synergistic application of AgCar:CHG demonstrated deep pilosebaceous gland penetration on Yucatan pig skin. The therapeutic concentration range of AgCar was determined to be between 120 × -150 × and 30 × -60 × dopage for MRSA and Cutibacterium acnes, respectively. A 1:1 therapeutic ratio of AgCar to CHG was found to have 100% bactericidal activity against both pathogens. Sutures coated with AgCar:CHG showed sustained antimicrobial activity against MRSA and Cutibacterium acnes, and were significantly more efficacious than antimicrobial sutures over the three- to four-day period (p < 0.01). Conclusions: This AgCar:CHG chemistry demonstrates deep skin penetration, extended elution, and broad-spectrum antimicrobial activity compared with commercially available options. This chemistry shows promise as an additional tool for the prophylaxis of surgical site infections.

Silver carboxylate-doped titanium dioxide-polydimethylsiloxane coating decreases Cutibacterium acnes adherence and biofilm formation on polyether ether ketone.

BACKGROUND CONTEXT: Cutibacterium acnes (C. acnes) is a gram-positive facultative anaerobe found in the deep sebaceous follicles of the skin on the shoulder and back. C. acnes has been increasingly recognized as a pathogen in spinal surgical site infection (SSI) especially in the presence of instrumentation. PURPOSE: This study assesses whether a silver carboxylate-doped titanium dioxide-polydimethylsiloxane (TiO2-PDMS) coating can decrease C. acnes adherence and biofilm formation on PEEK and four other commonly used spinal implant materials, stainless steel, cobalt chromium, titanium, and titanium alloy. STUDY DESIGN: We compared the adherence of C. acnes over 24 hours between uncoated, 95:5 TiO2 to PDMS ratio with 10× silver carboxylate coating and a 100% silver carboxylate coating on each implant material, which were uniformly saw cut and sterilized. Implants were then subjected to scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). METHODS: Samples were coated using 95:5 TiO2-PDMS 10× silver carboxylate, 100% silver carboxylate, or left uncoated. C. acnes was applied onto the samples and allowed to adhere for periods of 4, 8, 12, 16, or 20 hours. Nonadherent bacteria were then washed from the samples. These samples were then allowed to continue incubating for a total of 24 hours. SEM and confocal laser scanning microscope were used to visualize all samples for the presence of biofilm and quantification of C. acnes adherence at each time point. RESULTS: The 95:5 TiO2-PDMS 10× silver carboxylate coating was able to significantly decrease C. acnes adherence on PEEK after 8, 12, 16, and 20 hours of adherence. No statistical difference was found between the 95:5 TiO2-PDMS 10× silver carboxylate coating and the 100% silver carboxylate positive control. We previously observed extensive C. acnes biofilm formation on uncoated PEEK, but none on PEEK coated with either the 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating . Furthermore, no biofilm formation was observed on stainless steel, cobalt chromium, titanium, and titanium alloy coated with 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating. CONCLUSION: A 95:5 TiO2-PDMS 10× silver carboxylate coating decreases C. acnes adhesion and prevents biofilm formation on PEEK and other common orthopedic implant materials. CLINICAL SIGNIFICANCE: A 95:5 TiO2-PDMS 10× silver carboxylate coating may help decrease spinal SSI due to C. acnes, especially in procedures with instrumentation.

In vitro visualization and quantitative characterization of Pseudomonas aeruginosa biofilm growth dynamics on polyether ether ketone.

Prevention and treatment of orthopedic device-related infection (ODRI) is complicated by the formation of bacterial biofilms. Biofilm formation involves dynamic production of macromolecules that contribute to the structure of the biofilm over time. Limitations to clinically relevant and translational biofilm visualization and measurement hamper advances in this area of research. In this paper, we present a multimodal methodology for improved characterization of Pseudomonas aeruginosa grown on polyether ether ketone (PEEK) as a model for ODRI. PEEK discs were inoculated with P. aeruginosa, incubated for 4-48 h time intervals, and fixed with 10% neutral-buffered formalin. Samples were stained with fluorescent dyes to measure biofilm components, imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), and quantified. We were able to visualize and quantify P. aeruginosa biofilm growth on PEEK implants over 48 h. Based on imaging data, we propose a generalized growth cycle that can inform orthopedic diagnostic and treatment for this pathogen on PEEK. These results demonstrate the potential of using a combined CLSM and SEM approach for determining biofilm structure, composition, post-adherence development on orthopedic materials. This model may be used for quantitative biofilm analysis for other pathogens and other materials of orthopedic relevance for translational study of ODRI.

Silver Carboxylate as an Antibiotic-Independent Antimicrobial: A Review of Current Formulations, in vitro Efficacy, and Clinical Relevance.

The increasing prevalence of multi-drug resistant pathogens has led to a renewed focus on the use of silver as an antibiotic-independent antimicrobial. Unfortunately, the use of many silver formulations may be limited by an uncontrolled release of silver with the potential for significant cytotoxic effects. Silver carboxylate (AgCar) has emerged as an alternative formulation of silver with the potential to mitigate these concerns while still displaying significant bactericidal activity. This article reviews the efficacy of silver carboxylate formulations as a promising novel antibiotic-independent antimicrobial. This study was conducted through a search of five electronic databases (PubMed, Embase, MEDLINE, Cochrane Library, and Web of Science) for relevant studies up to September 2022. Searches were conducted for types of "silver carboxylate" formulations. Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. A review of the antimicrobial activity and cytotoxicity of silver carboxylate was compiled based on this search. Current body of data suggests that silver carboxylate shows promise as an emerging antibiotic-independent antimicrobial, with significant bactericidal effects while minimizing cytotoxicity. Silver carboxylate addresses several of the limitations of more primitive formulations, including controlled dosing and fewer negative effects on eukaryotic cell lines. These factors are concentration-dependent and largely rely on the vehicle system used to deliver it. Although several silver carboxylate-based formulations like titanium dioxide/polydimethylsiloxane (TiO2/PDMS) matrix-eluting AgCar have shown promising results in vitro, and could potentially be utilized independently or in conjunction with current and future antimicrobial therapies, there is a need for further in vivo studies to validate their overall safety and efficacy profile.

Review of Pre-Operative Skin Preparation Options Based on Surgical Site in Orthopedic Surgery.

Background: Surgical site infections (SSIs) are a primary contributor to surgical morbidity and mortality, causing a substantial financial burden on the healthcare system. Specifically, Cutibacterium acnes contributes greatly to infections in the shoulder and spine regions. Prevention of infection is crucial to improve patient outcomes and reduce costs. This article reviews current surgical skin preparation solutions, the unique distribution of organisms at common orthopedic surgical sites, and recommends solutions based on surgical location. Methods: A search of electronic databases (PubMed, MEDLINE, and Embase) was conducted for relevant literature until December 2020. Sources were compiled based on title and abstract, then full texts were read for possible inclusion. This review summarizes the most recent publications in the field of SSIs and preparation solutions. Results: The mechanism and efficacy of alcohol-, iodine-, and chlorhexidine-based preparations were reviewed, along with experimental preparations. This article identifies common colonization patterns for the shoulder, elbow, hip, knee, spine, foot, and ankle, and discusses recommendations for preparations based on current evidence. Recommendations: For shoulder and elbow operations, we recommend ChloraPrep™ (CareFusion, BD, El Paso, TX), DuraPrep™ (3M Health Care, St. Paul, MN), or Betadine® applied with 4 × 4 gauze sponge, three-day pre-operative benzyl peroxide, and application of 3% hydrogen peroxide before skin preparation. For the hip and knee, we recommend application of 2% chlorhexidine gluconate (CHG) cloth the night before and morning of surgery and either DuraPrep or iodine-alcohol skin prep prior to surgery. For spine surgeries, we recommended ChloraPrep. For foot and ankle, our recommendations are: ChloraPrep or DuraPrep, submersion of foot in 70% ethanol/10% isopropyl alcohol for five minutes prior to procedure, application with a bristled brush, and a second vigorous scrub with 4 × 4 soaked gauze. Conclusions: The current surgical skin preparations have both benefits and drawbacks. We recommend that orthopedic surgeons choose a skin preparation based on surgical site and prevalence of unique skin flora there.

Wound Irrigation in Orthopedic Open Fractures: A Review.

Background: Management of open fractures remains a major clinical challenge because of the higher energy involved in the injury, the greater local trauma, tissue necrosis, and extensive contamination. Even though early surgical debridement was thought to be critical, limited available operative techniques have minimized surgery in favor of early antibiotic administration. No clear agreement on the surgical approach, debridement, or irrigation technique exists. Surgeons continue to argue about the use of various fluids, the appropriate pressure of irrigation, antiseptics, and other factors. The current work reviews the available data and summarizes the capabilities of modern orthopedic irrigation solutions. Methods: To delineate available research on the topic, the PubMed database was queried for the most common techniques, fluid variables, and chemical adjuvants utilized in current open fracture and wound irrigation methodologies. Modes of delivery, volume, pressure, temperature, timing, solution type, and additives are evaluated in the context of known outcomes to determine which solutions may be preferable. Results: Various methods have been described with their own advantages as well as limitations. Particular solutions may apply to specific clinical scenarios, presence of implants, and degree of tissue contamination. Desired irrigation solutions are isotonic, non-toxic, non-hemolytic, transparent, sterilizable, efficient in removing debris and pathogens, as well as affordable; however, no current irrigant achieves all these desired characteristics. Conclusions: Despite being crucial for the healing of open fractures, there is no clear gold standard for irrigation. Although there are some novel irrigation solutions, there has been a paucity of research on finding new, safer, and more effective irrigation solutions that will promote wound healing and reduce infection.

Analysis of growth and biofilm formation of bacterial pathogens on frequently used spinal implant materials.

STUDY DESIGN: A microscopy-based investigation of the permissive factors leading towards bacterial adherence on commonly utilized spinal implants. OBJECTIVE: The adherence and subsequent colonization and biofilm formation of bacteria on orthopaedic implants represents one of the most serious problems facing orthopaedic surgeons. Once a biofilm is formed, surgeons may have to resort to implant removal, a strategy that may cause substantial patient morbidity and lead to additional cost to the healthcare system. This problem has been further compounded by the rise of antibiotic-resistant strains of bacterial pathogens. In this study, two commonly encountered bacterial pathogens in surgical site infections (SSI) were characterized for adherence pattern, density, and propagation on five commonly used spinal implant materials via scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results show that bacterial adherence is largely dependent on the microtopographical features observed on the surface of the materials tested. METHODS: Five commonly utilized spinal implant materials were inoculated with two of the most common nosocomial pathogens and visualized via scanning electron microscopy and confocal laser scanning microscopy. RESULTS: Analysis of 90 spinal implant pieces showed that even though no material showed the ability to prevent adherence of both pathogens tested, the presence of surface imperfections and rougher microtopography was found to harbor the most bacterial presence. CONCLUSION: Our data suggests that implants materials with uniform surface and minimal imperfections may reduce the ability of bacterial to adhere to implants. LEVEL OF EVIDENCE: Level I evidence: "Investigation of a diagnostic test".

Current Clinical Methods for Detection of Peri-Prosthetic Joint Infection.

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients.

Commonly Encountered Skin Biome-Derived Pathogens after Orthopedic Surgery.

Background: Normal skin microbiota influence susceptibility to surgical infections. The distribution of skin bacteria differs by anatomic site, and given the right conditions, almost any of these bacteria can become an opportunistic pathogen. Methods: This paper provides a thorough review of the most commonly encountered bacteria in various regions of the body and their isolation from operative incisions at those locations. These data may be useful in optimizing targeted antibiotic therapy for surgical site infections and provide a better understanding of the skin biome distribution at specific surgical sites. Conclusion: Typical skin-borne flora, surgical site infections, orthopedic infections by body part, and drug-resistant pathogens are reviewed.

Antimicrobial technology in orthopedic and spinal implants.

Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions.

Silver doped titanium oxide-PDMS hybrid coating inhibits Staphylococcus aureus and Staphylococcus epidermidis growth on PEEK.

Bacterial infection remains one of the most serious issues affecting the successful installation and retention of orthopedic implants. Many bacteria develop resistance to current antibiotics, which complicates or prevents traditional antibiotic-dependent eradication therapy. In this study, a hybrid coating of titanium dioxide and polydimethylsiloxane (PDMS) was synthesized to regulate the release of silver. The coatings were benefited from the antimicrobial activity of silver ion, the biocompatibility of titanium dioxide, and the flexibility of the polymer. Three studied silver doped coatings with different titanium dioxide-PDMS ratios effectively inhibited the attachment and growth of Staphylococcus aureus and Staphylococcus epidermidis in a dose-dependent manner. The coatings were successfully applied on the discs of polyether ether ketone (PEEK), a common spinal implant material and antibacterial property of these coatings was assessed via Kirby Bauer assay. More importantly, these selected coatings completely inhibited biofilm formation. The release study demonstrated that the release rate of silver from the coating depended on doping levels and also the ratios of titanium dioxide and PDMS. This result is crucial for designing coatings with desired silver release rate on PEEK materials for antimicrobial applications.