Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur. Fresh suspensions of Aims
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Aims. This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI
Aims. The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, 9,110 (66.9%) HAs and 4,502 (33.1%) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared with uncemented fixated prosthesis (p = 0.013). In patients with THA no statistical difference between cemented and uncemented prosthesis was registered, however after one year 2.4% of infections were detected in uncemented and 2.1% in cemented THA. In the subpopulation of HA after one year, 1.9% of infections were registered in cemented and 2.8% in uncemented HA. BMI (p = 0.001) and Elixhauser Comorbidity Index (p < 0.003) were identified as risk factors of periprosthetic joint infection (PJI), while in THA cemented prosthesis also demonstrated an increased risk within the first 30 days (hazard ratio (HR) = 2.73; p = 0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was statistically significantly reduced in patients treated by antibiotic-loaded cemented HA. Particularly for patients with multiple risk factors for the
Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance
Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection
Aims. Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods. Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI
Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting. Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Aims
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This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated. A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively.Aims
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Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the For the haematogenous infection, Aims
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The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20).Aims
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Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.Aims
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To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI). A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001).Aims
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This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Aims
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This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not.Aims
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We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.Aims
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The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.Aims
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To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Aims
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Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods.
99mTc-UBI29-41-Cy5 specificity for Aims
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Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem. Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references.Aims
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Objectives. Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability. Methods. Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy. Results. Hla-producing mutants caused substantial chondrocyte death compared with the toxin-deficient control (Hla-Hlb-Hlg-), whilst mutants producing Hlb and Hlg in the absence of Hla induced minimal chondrocyte death. Coronal studies established that Hla-induced chondrocyte death started in the superficial zone of cartilage and spread to deeper layers, whereas Hlb and Hlg toxins were without significant effect. Conclusion. This study identified Hla as a highly potent S. aureus toxin that caused rapid chondrocyte death in bovine cartilage, with other toxins or metabolic products produced by the bacteria playing a minor role. The identification of Hla in mediating chondrocyte death may assist in the
Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on
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Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells. Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks.Aims
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CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Aims
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This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy.Aims
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Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 106 or 43.0 (SD 8.4) x 105 colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 106 or 72.0 (SD 4.2) x 105 CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting.Aims
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The aim of this study was to assess the clinical application of, and optimize the variables used in, the BACH classification of long-bone osteomyelitis. A total of 30 clinicians from a variety of specialities classified 20 anonymized cases of long-bone osteomyelitis using BACH. Cases were derived from patients who presented to specialist centres in the United Kingdom between October 2016 and April 2017. Accuracy and Fleiss’ kappa (Fκ) were calculated for each variable. Bone involvement (B-variable) was assessed further by nine clinicians who classified ten additional cases of long bone osteomyelitis using a 3D clinical imaging package. Thresholds for defining multidrug-resistant (MDR) isolates were optimized using results from a further analysis of 253 long bone osteomyelitis cases.Objectives
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Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing.Objectives
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Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.Objectives
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Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI. A search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Aims
Materials and Methods
Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.
The purpose of this study was to examine the bactericidal efficacy of hydrogen peroxide (H2O2) on The effect of H2O2 was assessed by testing bactericidal effect, time course analysis, growth inhibition, and minimum bactericidal concentration. To assess the bactericidal effect, bacteria were treated for 30 minutes with 0%, 1%, 3%, 4%, 6%, 8%, or 10% H2O2 in saline or water and compared with 3% topical H2O2 solution. For time course analysis, bacteria were treated with water or saline (controls), 3% H2O2 in water, 3% H2O2 in saline, or 3% topical solution for 5, 10, 15, 20, and 30 minutes. Results were analyzed with a two-way analysis of variance (ANOVA) (p < 0.05).Objectives
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As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.Objectives
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Nasal carriers of Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of Objectives
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In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits. The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.Objective
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