Antibiotic-free antimicrobial poly (methyl methacrylate) bone cements: A state-of-the-art review

Navarro-López D.E., Garcia-Varela R., Ceballos-Sanchez O., Sanchez-Martinez A., Sanchez-Ante G., Corona-Romero K., Buentello-Montoya D.A., Elías-Zuñiga A., López-Mena E.R.

Nanostructured Zn 1-x Yb x O (0.0 ≤ x ≤ 0.1) powders were prepared by the solution method using polyvinyl alcohol (PVA) and sucrose. The effect of the ytterbium doping content on the structural, morphological, optical and antimicrobial properties was analyzed. X-ray diffraction (XRD) analysis revealed that the hexagonal wurtzite structure was retained, and no secondary phases due to doping were observed. The crystallite size was under 20 nm for all the Zn 1-x Yb x O (0.0 ≤ x ≤ 0.1) powders. The optical band gap was calculated, and the results revealed that this value increased with the ytterbium content, and the E g values varied from 3.06 to 3.10 eV. The surface chemistry of the powders was analyzed using X-ray photoelectron spectroscopy (XPS), and the results confirmed the oxidation state of ytterbium as 3+ for all the samples. Zn 1-x Yb x O (0.0 ≤ x ≤ 0.1) nanoparticles were tested as antimicrobial agents against Staphylococcus aureus and Escherichia coli , resulting in a potential antimicrobial effect at most of the tested concentrations. These results were used in an artificial neural network (ANN). The results showed that it is possible to generate a model capable of forecasting the absorbance with good precision (error of 1–2%). • Synthesis of ZnO and Yb-doped ZnO nanoparticles via polymerization-solution method • The ZnO and Yb-doped ZnO nanoparticles were characterized extensively. • ZnO and Yb-doped ZnO nanoparticles show effective antimicrobial activity against Staphylococcus aureus and Escherichia coli. • ANN was trained and tested with lab data. The model generated can predict absorbance with 1–2% error.

Mensah L.M., Love B.J.

A number of clinical studies have highlighted the success of antibiotics formulated at concentrations between 0 and 6% w /w into bone cements to address localized infections. Separately, some commercial manufacturers have produced gentamycin-infused bone cement mixtures as a countermeasure to infection. The anecdotal evidence suggests that antibiotic infused cements can help eradicate or delay the onset of infections. Quantifying the functionality of that response is more challenging. We have surveyed the literature to identify studies in which controlled drug release or mechanical behavioral assessments have been conducted on drug-infused cements. The focus here is on vancomycin (VAN) in part due to its higher potency relative to gentamycin and its more common usage for staph infections. Takeaways from the limited pool of research studies indicate that large fractions (>99%) of the infused vancomycin remain sequestered in the cement and aren't bioavailable after solidification. Antibiotic fluence ranged from 1 to 283 μg/cm 2 hr. The initial strength of the various antibiotic loaded samples as produced were 52–96 MPa. Simulated exposures in a fluid environment by submersion reduced the antibiotic loaded strengths between 3 and 29%. Some strength measurements were noted below the ASTM F451 standard for acrylic bone cement although drug releasing spacers likely have different requirements. The glassy behavior of the cured cement led to both vancomycin and gentamicin having low permeability and a burst response. Smaller drug molecules and more gel-like immobilization matrices with lower glass transition temperatures offer higher potential for larger and more comprehensive drug bioavailability. • ALBCs release antibiotic as a small but clinically effective burst dose. • More loading is linked with higher dose and weaker cement strength. • Future antibiotic release systems will use both diffusion and burst release schemes.

Kharat Z., Sadri M., Kabiri M.

One of the most substantial complications in orthopedic surgeries is implant associated infection. While the implant interface can be a permissive surface for bacterial colonization, an appropriate coating on the implant can effectively hinder biofilm formation. To this aim, henna and thyme extract loaded into a chitosan (CS)/polyethylene oxide (PEO) based nanofibrous hydrogel. CS/PEO/henna and CS/PEO/thymus extract nanofibers were fabricated via two-nozzle electrospinning. The proper weight ratio of CS/PEO/herbal extract was optimized. The appropriate ratio of CS/PEO and the most suitable extract concentrations was obtained to be 7/3 (v/v) and 1 % (v/v), respectively. Contact angle measurements showed an appropriate degree of hydrophilicity in all groups including herbal loaded electrospun nanosheets. Tensile strength measurements showed that inclusion of henna and thymus made minor changes in tensile strength and strain of herbal loaded nanofiber, compared to control CS/PEO fibers. Then antibacterial tests were performed and the fibers either by themselves or when used as coating on orthopedic screws exhibited a good inhibition zone against both gram negative and gram positive bacteria. The coatings showed no adverse effect on the red blood cells in leading to hemolysis. Cytocompatibility assay indicated that the prepared nanofibrous hydrogel coating was absolutely biocompatible as tested with fibroblast cells. The results of this study indicated that our henna and thyme extracts loaded CS/PEO coatings can be used in various medical fields such as wound dressing and implantation coating to prevent bacterial adhesion, growth and generally, infection.

Wekwejt M., Chen S., Kaczmarek-Szczepańska B., Nadolska M., Łukowicz K., Pałubicka A., Michno A., Osyczka A.M., Michálek M., Zieliński A.

Nanosilver-loaded PMMA bone cement doped with bioactive glasses is a novel cement developed as a replacement for conventional cements.

Hasan M., Altaf M., Zafar A., Hassan S.G., Ali Z., Mustafa G., Munawar T., Saif M.S., Tariq T., Iqbal F., Khan M.W., Mahmood A., Mahmood N., Shu X.

Despite of broad range application, the cost effective, highly stable and reproduceable synthesis of ZnO is needed, especially which can make it biosafe as well. Here, a unique bioinspired synthesis of ZnO nanoflowers (NFs) has been introduced using Withania coagulans extract as reducing agent. Different molar concentrations were assessed to counter the effect of structural, morphological, antibacterial activity and high efficiency of algae harvesting. The UV-spectroscopy authenticates the synthesis of ZnO NFs having Wurtzite hexagonal structure with the size in the range of 360–550 nm. While surface analysis revealed the presence of stabilizing agent like phenolic, amine, etc. on surface of ZnO NFs. These perineum ZnO NFs exhibited a stronger antibacterial with Gram-positive bacteria Staphylococcus aureus as compare to Gram-negative bacteria Pseudomonas aeruginosa and greater harvesting efficiency up to 94% on the account of greater surface area and unique surface chemistry, thus leading a new horizon of more efficient and effective applications for ethanol production. • Bioinspired synthesis of ZnO nanoflowers (NFs) via W coagulans • ZnO NFs of size ranging between 360-550 nm. • ZnO NFs exhibited a stronger antibacterial with Gram-positive S . aureus as compare to Gram-negative P . aeruginosa • ZnO NFs showed harvesting efficiency up to 94% on the account of greater surface area

Scheper H., Wubbolts J.M., Verhagen J.A., de Visser A.W., van der Wal R.J., Visser L.G., de Boer M.G., Nibbering P.H.

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.

Zhang X., Zhang Z., Shu Q., Xu C., Zheng Q., Guo Z., Wang C., Hao Z., Liu X., Wang G., Yan W., Chen H., Lu C.

Singh B.P., Ghosh S., Chauhan A.

Antimicrobial resistance is a major health issue inducing the inefficiency of antimicrobial drugs. Indeed, pathogenic microorganisms become resistant when frequently exposed to antimicrobial drugs. In particular, when bacteria are attached to a surface and expand as a biofilm, they become more resistant to antimicrobials because single or multiple bacterial species are embedded in a slimy extracellular polymeric substance that acts like a shield. Biofilms often contaminate medical devices and food industrial equipment, thus leading to infections and food spoilage. Here, we review the basics of biofilm development from a planktonic bacterium; signaling in biofilm and relationship with antimicrobial resistance; biofilm control and destruction strategies using quorum sensing inhibitors, ultrasound, acidic electrolyzed water, and enzymatic and combination killing; and emerging approaches, such as bacteriophage-mediated disruption and antimicrobial peptides to control bacterial biofilms.

Seyler T.M., Moore C., Kim H., Ramachandran S., Agris P.F.

Combating single and multi-drug-resistant infections in the form of biofilms is an immediate challenge. The challenge is to discover innovative targets and develop novel chemistries that combat biofilms and drug-resistant organisms, and thwart emergence of future resistant strains. An ideal novel target would control multiple genes, and can be inhibited by a single compound. We previously demonstrated success against Staphylococcus aureus biofilms by targeting the tRNA-dependent regulated T-box genes, not present in the human host. Present in Gram-positive bacteria, T-box genes attenuate transcription with a riboswitch-like element that regulates the expression of aminoacyl-tRNA synthetases and amino acid metabolism genes required for cell viability. PKZ18, the parent of a family of compounds selected in silico from 305,000 molecules, inhibits the function of the conserved T-box regulatory element and thus blocks growth of antibiotic-resistant S. aureus in biofilms. The PKZ18 analog PKZ18-22 was 10-fold more potent than vancomycin in inhibiting growth of S. aureus in biofilms. In addition, PKZ18-22 has a synergistic effect with existing antibiotics, e.g., gentamicin and rifampin. PKZ18-22 inhibits the T-box regulatory mechanism, halts the transcription of vital genes, and results in cell death. These effects are independent of the growth state, planktonic or biofilm, of the bacteria, and could inhibit emergent strains.

Mendili M., Essghaier B., Seaward M.R., Khadhri A.

Since lichens have been recognised as a potential natural source of bioactive substances, the aim of this study was to investigate the antimicrobial, lysozyme and antifungal effects of methanol, acetone and quencher extracts from four lichens: Diploschistes ocellatus, Flavoparmelia caperata, Squamarina cartilaginea and Xanthoria parietina. The results showed that the tested extracts had antimicrobial activity against Gram-positive and Gram-negative bacteria and anti-candida, and inhibit the spore germination of tested fungi. The different extracts varied in their effect as determined by the diameter of the inhibition zone, the highest values being observed with the methanol and acetone extracts (29.5 and 27.5 mm, respectively) for S. cartilaginea against Enterococcus faecalis. For powdered material (quencher), F. caperata showed the highest inhibition diameter (25.5 mm) against Staphylococcus aureus. The Minimum Inhibitory Concentration (MIC) values varied from 125 to 2000 μg mL−1. Methanol extracts of S. cartilaginea were more active against Enterobacter cloacae (MIC 125 µg mL−1) and Staphylococcus aureus (MIC 125 µg mL−1), and also affected lysozyme activity against Staphylococcus aureus, as well as the morphology of fungal hyphae. This study demonstrated that the investigated species are a potential source of bioactive compounds which are potentially important antimicrobial agents.

Farhan-Alanie M.M., Burnand H.G., Whitehouse M.R.

Aims This study aimed to compare the effect of antibiotic-loaded bone cement (ALBC) versus plain bone cement (PBC) on revision rates for periprosthetic joint infection (PJI) and all-cause revisions following primary elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods MEDLINE, Embase, Web of Science, and Cochrane databases were systematically searched for studies comparing ALBC versus PBC, reporting on revision rates for PJI or all-cause revision following primary elective THA or TKA. A random-effects meta-analysis was performed. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42018107691). Results Nine studies and one registry report were identified, enabling the inclusion of 371,977 THA and 671,246 TKA. Pooled analysis for THA demonstrated ALBC was protective against revision for PJI compared with PBC (relative risk (RR) 0.66, 95% confidence interval (CI) 0.56 to 0.77; p < 0.001), however, no differences were seen for all-cause revision rate (RR 0.62, 95% CI 0.35 to 1.09; p = 0.100). For TKA, there were no significant differences in revision rates for PJI or all causes between ALBC and PBC (RR 0.92, 95% CI 0.59 to 1.45; p = 0.730, and RR 0.73, 95% CI 0.53 to 1.02; p = 0.060, respectively). Conclusion ALBC demonstrated a protective effect against revision for PJI compared with PBC in THA with no difference in all-cause revisions. No differences in revision rates for PJI and all-cause revision between ALBC and PBC for TKA were observed. Cite this article: Bone Joint J 2021;103-B(1):7–15.

Li R., Li X., Ni M., Zheng Q., Zhang G., Chen J.

Hip aspirations used to detect a periprosthetic joint infection (PJI) are usually performed under fluoroscopy or ultrasound. The aim of this study was to evaluate the results of simply using anatomic landmarks for aspiration and detecting PJI without the use of any complicated technologies. The authors retrospectively reviewed a total of 186 consecutive hip aspirations performed between April 2015 and December 2018. All patients were suspected to have infections after total hip arthroplasty. The procedures were performed with the patients in the supine position. The authors aimed to aspirate at the neck of the prosthesis. They located the y-axis of the puncture point approximately 2 to 3 cm lateral to the pulse of the femoral artery in the region of the inguinal ligament. The x-axis was estimated by using the pubic symphysis or greater trochanter according to an anteroposterior radiograph of the hip joint. The aspiration failure rate, incidence of complications, and culture results were recorded. The overall aspiration failure rate was 3.8% (7 of 186). No obvious complications related to aspiration were observed. The saline lavage and reaspiration rate was 45.3% (81 of 179) due to dry taps. The sensitivity, specificity, positive predictive value, and negative predictive value of the remaining 169 patients with definite diagnoses were 0.781 (95% CI, 0.678-0.860), 0.939 (95% CI, 0.857-0.977), 0.931 (95% CI, 0.841-0.975), and 0.802 (95% CI, 0.706-0.874), respectively. Anatomic landmark-guided hip aspiration was a convenient method that could provide satisfactory detection of PJI. [Orthopedics. 2021;44(1):e85-e90.].

McNally M., Sousa R., Wouthuyzen-Bakker M., Chen A.F., Soriano A., Vogely H.C., Clauss M., Higuera C.A., Trebše R.

Aims The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. Conclusion The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25.

Huang Q., Xu S., Ouyang Z., Yang Y., Liu Y.

Mimicking the hierarchical structure of nacre in artificial materials is a promising approach to obtain high mechanical performance. In this work, nacre-inspired lamella-structured Ti-Ta composites were fabricated by successive spark plasma sintering, mechanical processing and annealing. The specimen sintered at 1200 °C and then hot rolled with 60% height reduction exhibited multi-scale lamellar microstructure. At micro-scale, the composite was composed of alternate Ti-enriched and Ta-enriched micro-bands. At nano-scale, highly-ordered lamellar structures consisted of Ti-enriched and Ta-enriched nano-lamellae were found near Ti/Ta micro-bands. The biomimetic-structured Ti-Ta composite possessed appropriate combination of strength (1030 MPa ultimate tensile strength) and ductility (10.2% elongation), which is much stronger than pure Ti and comparably strong as Ti-6Al-4 V. Moreover, the biomimetic-structured Ti-Ta composite possessed low modulus (80.6 GPa). In vitro cell culture experiment revealed that the biomimetic-structured Ti-Ta composite was cytocompatible, evidenced by the well-spread morphology and favorable growth of human bone mesenchymal stem cells (hBMSCs) on material surface. A rat femoral fracture model was employed to evaluate the therapeutic performance of biomimetic-structured Ti-Ta composite implant on fracture healing compared to that of pure Ti. In vivo results showed that the composite implant enhanced fracture healing in rats. Together, the findings obtained in the current work suggest that mimicking the hierarchical structure of nacre in Ti-Ta composite is an effective way for material strengthening. Moreover, the biomimetic-structured Ti-Ta composite with high strength, good ductility, low modulus and favorable biocompatibility is promising for load-bearing applications in orthopedic and dental area. • Biomimetic-structured Ti Ta composite was prepared by spark plasma sintering and hot rolling. • Ti Ta composite exhibited nacre-inspired lamella-structure at both micro- and nano-scale. • Ti Ta composite promoted bone fracture healing in rats compare to Ti.

Villa J.M., Pannu T.S., Theeb I., Buttaro M.A., Oñativia J.I., Carbo L., Rienzi D.H., Fregeiro J.I., Kornilov N.N., Bozhkova S.A., Sandiford N.A., Piuzzi N.S., Higuera C.A., Kendoff D.O.

AbstractBackground There is scarce literature describing pathogens responsible for periprosthetic joint infections (PJIs) around the world. Therefore, we sought to describe periprosthetic joint infection causative organisms, rates of resistant organisms, and polymicrobial infections at 7 large institutions located in North/South America and Europe. Methods We performed a retrospective study of 654 periprosthetic hip (n = 361) and knee (n = 293) infections (January 2006 to October 2019) identified at Cleveland Clinic Ohio/Florida in the United States (US) (n = 159), Hospital Italiano de Buenos Aires in Argentina (n = 99), Hospital Asociación Española in Uruguay (n = 130), Guy's and St Thomas' Hospital in the United Kingdom (UK) (n = 103), HELIOS Klinikum in Germany (n = 59), and Vreden Institute for Orthopedics in St. Petersburg, Russia (n = 104). Analyses were performed for the entire cohort, knees, and hips. Alpha was set at 0.05. Results Overall, the most frequent organisms identified were Staphylococcus aureus (24.8%) and Staphylococcus epidermidis (21.7%). The incidence of organisms resistant to at least one antibiotic was 58% and there was a significant difference between hips (62.3%) and knees (52.6%) (P = .014). Rates of resistant organisms among countries were 37.7% (US), 66.7% (Argentina), 71.5% (Uruguay), 40.8% (UK), 62.7% (Germany), and 77.9% (Russia) (P < .001). The overall incidence of polymicrobial infections was 9.3% and the rates across nations were 9.4% in the US, 11.1% in Argentina, 4.6% in Uruguay, 4.9% in UK, 11.9% in Germany, and 16.3% in Russia (P = .026). Conclusion In the evaluated institutions, S aureus and S epidermidis accounted for almost 50% of all infections. The US and the UK had the lowest incidence of resistant organisms while Germany and Russia had the highest. The UK and Uruguay had the lowest rates of polymicrobial infections.

Fan M., Ren Y., Zhu Y., Zhang H., Li S., Liu C., Lv H., Chu L., Hou Z., Zhang Y., Pan H., Cui X., Chen W.

Minasov B.S., Yakupov R.R., Akbashev V.N., Bilyalov A.R., Minasov T.B., Valeev M.M., Mavlyutov T.R., Karimov K.K., Berdin A.R.

Introduction The advancement of surgery is set against a backdrop of continuous development and surgical innovations have transformed the way clinical care is delivered. Revision surgery might be required to  address complications of primary arthroplasty. The first stage of revision arthroplasty would involve removal of  an  implant and placement of an antibiotic-impregnated cement spacer to maintain the joint space and stability, prevent soft tissue retraction, provide local antibiotic release and preserve bone tissue for revision implantation at the final stage of revision. Custom-made articulating spacers are a promising tool for optimizing the first stage of revision arthroplasty.The objective was to summarize the current data and present comprehensive information about spacers used in two-stage revision arthroplasty including manufacturing techniques, physical and chemical properties, clinical applications, the possibility of customization within the first stage of revision arthroplasty, current and promising directions for research.Material and methods The original literature search was conducted on key resources including Scientific Electronic Library (www.elibrary.ru), the National Library of Medicine (www.pubmed.org), the Cochraine Library (www.cochranelibrary.com) between 2018 and 2023 using search words and phrases: total arthroplasty, complications, revision arthroplasty, articulating spacer, periprosthetic joint infection, additive manufacturing, 3D printing.Results A comparative analysis of factory supplied, home-made, dynamic and static spacer models showed that the choice of articulating spacers for revision arthroplasty of major joints is of great relevance. Advantages of factory-made spacers include standardized range of sizes, the reliability and availability for medical institutions. They are characterized by limited use in repair of severe bone defects.Discussion Custom-made articulating spacers enable specific tailoring to accommodate individual defects. Despite high expectations from custom-made spacers, development of optimal technologies for rapid prototyping is essential. Investments in research and development in this area have the potential to create innovative solutions that can significantly improve the results of revision arthroplasty.Conclusion The paper explores the importance of systemization of knowledge about spacers and the role of new research in improving the design and functionality. Progress in the field of materials science, additive technologies and a personalized approach to spacer manufacturing can expand possibilities of  revision arthroplasty and the effectiveness. Personalized approaches and improved methods of local drug delivery that provide controlled release of antibiotics can improve the results of treatment of periprosthetic joint infections.

Katsaros I., Echeverri E., Engqvist H., Persson C., Xia W.

Injectable poly (methyl methacrylate) (PMMA) bone cements are widely used in orthopaedics to stabilize fractures and for implant fixation. However, bacterial attachment to bone cements leads to significant complications that can create a need for implant revision. Common attempts at reducing bacterial attachment are through the addition of antibiotics or antibacterial nanometals to the bone cements. However, clinical data is inconclusive on the effectiveness of antibiotic-loaded bone cements and a negative osteoblastic response has been reported for certain additive concentrations. There is therefore a need for an additive that can positively affect osteoblastic behaviour while inhibiting bacterial attachment. Silicon nitride (Si3N4) could be such an additive, with initial studies showing promise in achieving antipathogenic properties. The aim of this study was hence to investigate the possibility of creating a bone cement that can support osteoblast growth while reducing bacterial attachment by introducing silicon nitride powders into an injectable PMMA cement. To this end, commercially available bone cements were doped with 5%, 10% and 20% weight/weight (w/w) of Si3N4. Their mechanical properties were examined through compression testing and their radiopacity was evaluated through fluoroscopy imaging. The samples that fulfilled compressive strength requirements had their biological properties tested using Staphylococcus epidermidis bacteria for antibacterial properties and MC3T3-E1 preosteoblasts for the examination of cytotoxicity. Bone cements that were doped with up to 20% w/w Si3N4 were radiopaque (only 13% reduction in optical density compared to radiopaque controls) and retained their compressive strength (85.35 ± 2.1 MPa compared to 83.4 ± 1.9 MPa for the commercial cements), while significantly reducing bacterial attachment by more than 90% compared to commercial cements and achieving a similar level of preosteoblast metabolic activity. This study supports further evaluation of Si3N4 as an additive to injectable bone cements as a way to create mechanically stable, radiopaque, bacteriostatic bone cements that could improve osteointegration.

Kan Y., Guo R., Xu Y., Han L., Bu W., Han L., Chu J.

Abstract Objective The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). Methods Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. Results The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). Conclusion In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

Gao Z., Kan Y., Xie Y., Guo R., Li C., Asilebieke A., Xu Y., Chu J.

Antibiotic-loaded bone cements are widely used in orthopedic surgery. However, they present issues such as a short antibiotic release time and antibiotic resistance. These challenges necessitate the development of novel antibacterial bone cements. Non-leaching bone cement containing antibacterial motifs represents a promising advancement in this direction. Antibacterial motifs are incorporated into the cement either covalently or non-covalently, and while they will not be released, they will still exhibit surface antibacterial activity. This review comprehensively examines the structure and antimicrobial activity of prevalent non-leaching antimicrobial bone cements. Additionally, it delves into the characteristics of current methods employed for detecting surface antimicrobial activity. Finally, the future research direction of non-leaching antibacterial bone cement is discussed, with a specific focus on innovative antibacterial motifs, the mechanisms underlying non-leaching antibacterial properties, and the potential synergies achievable by combining non-leaching antibacterial bone cement with traditional antibiotics.

Velnar T., Bosnjak R., Gradisnik L.

Background: Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations. Methods: The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed. Results: All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection. Conclusions: Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects.