Hand-mixed and premixed antibiotic-loaded bone cement have similar homogeneity.
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ABSTRACT:
SUBMITTER: McLaren AC
PROVIDER: S-EPMC2690765 | biostudies-other | 2009 Jul
REPOSITORIES: biostudies-other
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Project description:New antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix. The antibiotic-loaded bone cement exhibited greater efficacy than currently used antibiotic-loaded bone cements against staphylococcal bone infections in rats. Potent and locally delivered antibiotic-eluting polymers may help address antimicrobial resistance.
| S-EPMC10101771 | biostudies-literature
Project description:Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.
| S-EPMC7390691 | biostudies-literature
Project description:Background and purposeThe purpose of this study was to investigate the effect of incorporating chitosan (Ch) and chitosan oligosaccharides (ChO) into the commercially premixed antibiotic-loaded bone cement (ALBC). We compare antibiotic release profiles, antibacterial activity, and mechanical properties among different ALBC formulations. The hypothesis was that increasing the amount of Ch and ChO in the cement mixture would increase the antibiotics released and bacterial control. ALBC mixed with Ch or ChO may create a greater effect due to its superior dissolving property.Materials and methodsThe bone cement samples used in this project were made from Copal® G+V composed of vancomycin and gentamicin. To prepare the Ch and the ChO mixed bone cement samples, different amounts of Ch and ChO were added to the polymethylmethacrylate matrix with three concentrations (1%, 5%, and 10%). Drug elution assay, antimicrobial assay, in vitro cytotoxicity, and mechanical properties were conducted.ResultsBone cement samples made from Copal® G+V alone or combined with Ch or ChO can release vancomycin and gentamicin into the phosphate-buffered saline. Mixing ChO into the bone cements can increase the amount of drug released more than Ch. ChO 10% gave the highest amount of antibiotics released. All samples showed good antibacterial properties with good biocompatibility in vitro. The microhardness values of the Ch and ChO groups increased significantly compared to the control group. In all groups tested, the microhardness of bone cements was reduced after the drug eluted out. However, this reduction of the Ch and ChO groups was in line with the control.InterpretationVarious attempts have been made to improve the ALBC efficacy. In our study, the best bone cement formulation was bone cement mixed with ChO (10%), which had the highest drug release profiles, was biocompatible, and contained antibacterial properties with acceptable mechanical properties. This phenomenon could result from the superior water solubility of the ChO. When ChO leaves the bone cement specimens, it generates pores that could act as a path that exposes the bone cement matrix to the surrounding medium, increasing antibiotic elution. From all above, ChO is a promising substance that could be added to ALBC in order to increase the drug elution rate. However, more in vitro and in vivo experiments are needed before being used in the clinic.
| S-EPMC9710798 | biostudies-literature
Project description:The purpose of this study was to investigate the effects of addition of antibiotics into cement powder on the shear properties of the cement-metal interface. The approach involved adding 800 mg of teicoplanin to 40 g bone cement powder in the t-800 group, 1,600 mg teicoplanin in the t-1,600 group, and no antibiotic in the control group. Industrially prepared bone cement containing 500 mg of gentamicin was used as group g-500. Each group consisted of ten samples. Cement-metal interfaces were produced using metal discs with porous surfaces (1 microm) and templates at the third minute. Shear stability of specimens was measured in a material testing machine. The ANOVA test was used for comparison between the mean shear results of each group. Results showed that mean shear stress to failure values were 12.28+/-3.35 MPa for the control group, 11.72+/-3.09 MPa for the t-800 group, 13.25+/-2.36 MPa for the t-1,600 group and 13.09+/-2.58 MPa for the g-500 group. No statistically significant differences were found between results of the groups. Results of the study have proven that addition of 1,600 mg of teicoplanin or 500 mg gentamycin in 40 g of bone cement does not decrease the shear strength at the cement-metal interface significantly on the day of application.
| S-EPMC2532260 | biostudies-other
Project description:PurposeAntibiotic-loaded bone cement (ALBC) was usually used to prevent periprosthetic joint infection (PJI) in primary total knee arthroplasty (PTKA), but whether to use ALBC or plain bone cement in PTKA remains unclear. We aimed to compare the occurrence rate of PJI using two different cements, and to investigate the efficacy of different antibiotic types and doses administered in preventing surgical site infection (SSI) with ALBC.MethodsThe availability of ALBC for preventing PJI was evaluated by using a systematic review and meta-analysis referring to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Existing articles until December 2021 involving PTKA patients with both ALBC and plain bone cement cohorts were scanned by searching "total knee arthroplasty", "antibiotic-loaded cement", "antibiotic prophylaxis", "antibiotic-impregnated cement" and "antibiotic-laden cement" in the database of PubMed/MEDLINE, Embase, Web of Science and the Cochrane Library. Subgroup analysis included the effectiveness of different antibiotic types and doses in preventing SSI with ALBC. The modified Jadad scale was employed to score the qualities of included articles.ResultsEleven quantitative studies were enrolled, including 34,159 knees undergoing PTKA. The meta-analysis results demonstrated that the use of prophylactic ALBC could significantly reduce the prevalence of deep incisional SSI after PTKA, whereas there was no significant reduction in the rate of superficial incisional SSI. Moreover, gentamicin-loaded cement was effective in preventing deep incisional SSI, and the use of high-dose ALBC significantly reduced the rate of deep incisional SSI after PTKA. Besides, no significant adverse reactions and complications were stated during the use of ALBC in PTKA.ConclusionThe preventive application of ALBC during PTKA could reduce the rates of deep PJI. Furthermore, bone cement containing gentamicin and high-dose ALBC could even better prevent deep infection after PTKA. However, the existing related articles are mostly single-center and retrospective studies, and further high-quality ones are needed for confirmation.
| S-EPMC9751532 | biostudies-literature
Project description:BackgroundPolymethylmethacrylate (PMMA) bone cement loaded with enoxaparin sodium (PMMA@ES) has been increasingly highlighted to affect the bone repair of bone defects, but the molecular mechanisms remain unclear. We addressed this issue by identifying possible molecular mechanisms of PMMA@ES involved in femoral defect regeneration based on bioinformatics analysis and network pharmacology analysis.MethodsThe upregulated genes affecting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were selected through bioinformatics analysis, followed by intersection with the genes of ES-induced differentiation of BMSCs identified by network pharmacology analysis. PMMA@ES was constructed. Rat primary BMSCs were isolated and cultured in vitro in the proliferation medium (PM) and osteogenic medium (OM) to measure alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and the expression of RUNX2 and OCN using gain- or loss-of-function experiments. A rat femoral bone defect model was constructed to detect the new bone formation in rats.ResultsATF2 may be a key gene in differentiating BMSCs into osteoblasts. In vitro cell assays showed that PMMA@ES promoted the osteogenic differentiation of BMSCs by increasing ALP activity, extracellular matrix mineralization, and RUNX2 and OCN expression in PM and OM. In addition, ATF2 activated the transcription of miR-335-5p to target ERK1/2 and downregulate the expression of ERK1/2. PMMA@ES induced femoral defect regeneration and the repair of femoral defects in rats by regulating the ATF2/miR-335-5p/ERK1/2 axis.ConclusionThe evidence provided by our study highlighted the ATF2-mediated mechanism of PMMA@ES in the facilitation of the osteogenic differentiation of BMSCs and femoral defect regeneration.
| S-EPMC10470168 | biostudies-literature
Project description:Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.
| S-EPMC8941180 | biostudies-literature
Project description:IntroductionThe current evidence on the efficacy of antibiotic-loaded bone cement (ALBC) in reducing the risk of periprosthetic joint infections (PJI) after primary joint reconstruction is insufficient. In several European countries, the use of ALBC is routine practice unlike in the USA where ALBC use is not approved in low-risk patients. Therefore, we designed a double-blinded pragmatic multicentre register-based randomised controlled non-inferiority trial to investigate the effects of ALBC compared with plain bone cement in primary total knee arthroplasty (TKA).Methods and analysisA minimum of 9,172 patients undergoing full-cemented primary TKA will be recruited and equally randomised into the ALBC group and the plain bone cement group. This trial will be conducted in Norwegian hospitals that routinely perform cemented primary TKA. The primary outcome will be risk of revision surgery due to PJI at 1-year of follow-up. Secondary outcomes will be: risk of revision due to any reason including aseptic loosening at 1, 6, 10 and 20 years of follow-up; patient-related outcome measures like function, pain, satisfaction and health-related quality of life at 1, 6 and 10 years of follow-up; risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions at 1, 6, 10 and 20 years of follow-up; cost-effectiveness of routine ALBC versus plain bone cement use in primary TKA. We will use 1:1 randomisation with random permuted blocks and stratify by participating hospitals to randomise patients to receive ALBC or plain bone cement. Inclusion, randomisation and follow-up will be through the Norwegian Arthroplasty Register.Ethics and disseminationThe trial was approved by the Western Norway Regional Committees on Medical and Health Research Ethics (reference number: 2019/751/REK vest) on 21 June 2019. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT04135170.
| S-EPMC7845702 | biostudies-literature
Project description:Metastatic and primary bone tumors are malignant tumors affecting the skeleton. Although the prognosis of patients with these tumors has improved with the development of effective chemotherapy, the challenges of local recurrence, subsequent osteolysis, degradation of bone strength and unresectable tumors persist. Local control of these tumors is therefore a key strategy to address these limitations. The third-generation bisphosphonate (BP), zoledronic acid (ZOL), has been demonstrated to reduce osteoclasts and exhibited potent antitumor effects in a number of malignancies. Hydroxyapatite (HA) and polymethyl methacrylate (PMMA) bone cement are used in orthopedic surgery as bone graft substitutes, for implant arthroplasty and bone strengthening, and as a sustained-release system for drugs such as antibiotics. At present, the antitumor effects of ZOL-loaded HA in vitro or in vivo or of ZOL-loaded bone cement in vivo have not been described. Therefore, the present study assessed the effects of ZOL-loaded HA and bone cement in malignant tumor cells. The two materials exerted strong antitumor effects against osteosarcoma, fibrosarcoma, synovial sarcoma, renal cancer, prostate cancer and lung cancer cells upon releasing ZOL. The antitumor effects of ZOL-loaded HA were less potent compared with those of ZOL-loaded bone cement, possibly as BPs exhibit higher affinity to HA. ZOL-loaded bone cement also exerted antitumor effects against pulmonary metastases and primary lesions, without exhibiting systemic toxicity in vivo. These results demonstrate that these materials may be beneficial for the treatment of malignant bone tumors, including metastatic bone tumors. In addition, as these materials are already in clinical use, such applications may be easily implemented.
| S-EPMC5529883 | biostudies-other
Project description: Not available
| S-EPMC10965272 | biostudies-literature