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Inverardi N, Serafim MF, Sekar A, Fujino K, Ferreira M, Marzouca A, Nagler E, Muratoglu OK, Oral E. Wear-resistant antibacterial UHMWPE-based implant materials obtained by radiation crosslinking. Biomater Sci 2025; 13:2422-2434. [PMID: 40131351 DOI: 10.1039/d4bm01663g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
The crosslinking of ultrahigh molecular weight polyethylenes (UHMWPEs) by irradiation has been employed for decades to enhance the wear resistance of these materials when used as a load-bearing implant component for joint arthroplasty. This surgical procedure can restore the mobility of patients affected by severe arthritis by the implantation of an artificial joint made of an articulating pair and a bearing component. While the surgery is usually successful, one of the most severe complications is peri-prosthetic joint infection (PJI), which can be extremely difficult to treat and eradicate. The use of UHMWPEs as a platform for the local delivery of antibiotics in addition to their structural function could be extremely beneficial for the improvement in the outcome of PJIs. In this study, we investigated whether irradiation can be used to sterilize and crosslink antibiotic-loaded UHMWPEs, and its effect on the drug eluting and antibacterial properties of these materials. We found that the antibiotics gentamicin sulfate and vancomycin hydrochloride were stable in irradiated UHMWPEs and did not hinder crosslinking of the UHMWPE matrix. Effective crosslinking led to optimal wear resistance, which was comparable to that of clinically available UHMWPEs. Sustained drug release was observed for an extended duration (up to six months) and both the drug eluents and eluted material surfaces showed antibacterial activity against Staphylococcus aureus, the most common causative bacterium for PJIs.
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Affiliation(s)
- Nicoletta Inverardi
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02114, USA
| | - Maria F Serafim
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | - Amita Sekar
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02114, USA
| | - Keita Fujino
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | - Matheus Ferreira
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | - Anthony Marzouca
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | - Emma Nagler
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | - Orhun K Muratoglu
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02114, USA
| | - Ebru Oral
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02114, USA
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Cao Y, Tang P, Chai H, Ma W, Lin B, Zhu Y, Abdirahman A, Xiao W, Zhang J, Li Y, Liu S, Wen T. The application of antibiotic-loaded bone cement in preventing periprosthetic joint infection: an umbrella review. J Orthop Traumatol 2025; 26:23. [PMID: 40249535 PMCID: PMC12008095 DOI: 10.1186/s10195-025-00839-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 03/22/2025] [Indexed: 04/19/2025] Open
Abstract
OBJECTIVES The purpose of this study was to provide thorough, understandable and precise evidence for the clinical use of antibiotic-loaded bone cement (ALBC) in preventing periprosthetic joint infection (PJI). METHODS We evaluated the effectiveness of ALBC in preventing PJI by conducting an umbrella review of existing meta-analysis. Four databases, PubMed/MEDLINE, Cochrane Library, Embase and Web of Science, were searched until May 2024. Two reviewers were reviewers for literature screening, and data were extracted independently. AMSTAR 2 guideline and GRADE were also used for quality evaluation. The clinical outcomes were evaluated for effectiveness by several indicators, including surface infection rate (SIR), deep infection rate (DIR), total infection rate (TIR), unadjusted/adjusted all-cause revision rate, and revision rate for PJI. RESULTS We synthesized the results of ten meta-analyses. Two meta-analyses had high AMSTAR 2 scores, two had moderate AMSTAR 2 ratings, three had critically low AMSTAR 2 scores, and the remaining meta-analyses had low AMSTAR 2 ratings. In terms of postoperative surgical site infection and revision rate, SIR (OR 1.50, 95% CI 1.14, 1.99, P = 0.004, I2 = 0%), unadjusted all-cause revision rate (RR 1.44, 95% CI 1.08, 1.90, P = 0.011, I2 = 91.8%) and adjusted all-cause revision rate (HR 1.21, 95% CI 1.12, 1.31, P < 0.001, I2 = 0%) in ALBC group were significantly higher than those in non-antibiotic-loaded bone cement (NALBC) group. ALBC group was significantly lower than NALBC group in DIR (OR 0.53, 95% CI 0.39, 0.70, P < 0.0001, I2 = 57%), (RR 0.506, 95% CI 0.341, 0.751, P = 0.001, I2 = 0%) and revision for PJI (RR 0.721, 95% CI 0.628, 0.828, P = 0, I2 = 53%). There was no statistical difference in total infection rate (TIR) between the ALBC group and the NALBC group (OR 0.81, 95% CI 0.51, 1.28, P = 0.37, I2 = 73%). CONCLUSIONS On the basis of the results of our analysis, we do not believe that ALBC is more effective than NALBC in preventing PJI after primary total joint arthroplasty (PTJA). No statistically significant difference was found on TIR between the two groups, although it was lower in the ALBC group. In addition, the DIR and revision for PJI are significantly lower in the ALBC group, but the results are of low quality, which calls for high-quality and large-sample studies in the future.
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Affiliation(s)
- Yangbin Cao
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Peiyuan Tang
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hua Chai
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Wenbo Ma
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Bin Lin
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Ying Zhu
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Ahmed Abdirahman
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Wenfeng Xiao
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jun Zhang
- The First People's Hospital of Changde City, Changde Hospital, Xiangya Medical College, Central South University, Changsha, 415000, China
| | - Yusheng Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Shuguang Liu
- Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Ting Wen
- Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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Lin YC, Chang CH, Hu CC, Liang YC, Hsieh PH, Lee SH, Lin SH. Safety of vancomycin-loaded cement spacers for treating gram-positive periprosthetic joint infections in two-stage resection arthroplasty among patients with renal insufficiency. BMC Musculoskelet Disord 2025; 26:65. [PMID: 39827138 PMCID: PMC11742531 DOI: 10.1186/s12891-025-08324-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND The standard treatment for periprosthetic joint infections (PJI) typically involves a two-stage resection arthroplasty using antibiotic-loaded bone cement (ALBC) spacers. This study hypothesizes that there is no significant correlation between antibiotic levels in blood and synovial fluid and the patient's kidney function, and that the success rates of staged resection arthroplasty are comparable between groups, specifically targeting gram-positive bacterial infections. METHODS This retrospective review included patients treated from 2017 to 2022 with two-stage arthroplasty using vancomycin-loaded ALBC spacers, selectively targeting gram-positive infections. Patients with non-gram-positive infections or those with allergies or treatments affecting serum antibiotic levels were excluded. The study assessed comorbidities, renal function, specifics of the spacers, and vancomycin concentrations in joint fluid and blood. RESULTS Among 62 PJI cases analyzed (22 hips and 40 knees), 34 patients (54.8%) had renal insufficiency (RI), associated with significantly lower albumin (2.64 g/dL vs. 3.43 g/dL, p < 0.05) and estimated glomerular filtration rate (eGFR) (58.17 mL/min/1.73 m² vs. 121.74 mL/min/1.73 m², p < 0.05). No significant differences were found in comorbidities, antibiotic regimen, or the weight of the ALBC spacers between the groups (p > 0.05). Both groups exhibited high vancomycin levels in joint fluid, with peak blood vancomycin levels inversely correlated with eGFR (coefficient - 3.612, 95% CI -8.543 to -2.753, p < 0.001). RI patients displayed higher peak blood vancomycin levels (1.23-5.43 mg/L) but remained below toxicity thresholds. The infection-free interval, aseptic revision rates, and bacterial profiles specific to gram-positive species showed no significant differences between the groups. CONCLUSION Systemic absorption of vancomycin from ALBC spacers was evident in patients with RI and inversely correlated with eGFR, yet remained well below toxic thresholds across all patients. These findings suggest that the use of vancomycin-loaded ALBC spacers appears to be safe for managing gram-positive infections in patients with varying renal function. Additionally, renal insufficiency did not adversely affect the infection-free interval, aseptic revision rates, or bacterial diversity. LEVEL OF EVIDENCE III.
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Affiliation(s)
- Yu-Chih Lin
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 1001 University Road, Hsinchu City, 300, Taiwan
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University (CGU), 259 Wen-Hwa 1st Road, Kweishan, Taoyuan City, Taiwan
| | - Chih-Hsiang Chang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University (CGU), 259 Wen-Hwa 1st Road, Kweishan, Taoyuan City, Taiwan
| | - Chih-Chien Hu
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University (CGU), 259 Wen-Hwa 1st Road, Kweishan, Taoyuan City, Taiwan
| | - Yung-Chieh Liang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
| | - Pang-Hsin Hsieh
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University (CGU), 259 Wen-Hwa 1st Road, Kweishan, Taoyuan City, Taiwan
| | - Sheng-Hsun Lee
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan.
- Bone and Joint Research Center, Chang Gung Memorial Hospital (CGMH), No. 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan.
- College of Medicine, Chang Gung University (CGU), 259 Wen-Hwa 1st Road, Kweishan, Taoyuan City, Taiwan.
| | - Sheng-Hsuan Lin
- Institute of Statistics, National Yang Ming Chiao Tung University, 1001 University Road, Hsinchu City, 300, Taiwan.
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Coleman HJ, Yang Q, Robert A, Padgette H, Funke HH, Catalano CE, Randolph TW. Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release. J Pharm Sci 2024; 113:3238-3245. [PMID: 39173744 DOI: 10.1016/j.xphs.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 08/24/2024]
Abstract
Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.
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Affiliation(s)
- Holly J Coleman
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO, 80303, USA
| | - Qin Yang
- Department of Pharmaceutical Chemistry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Amanda Robert
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO, 80303, USA
| | - Hannah Padgette
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO, 80303, USA
| | - Hans H Funke
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO, 80303, USA
| | - Carlos E Catalano
- Department of Pharmaceutical Chemistry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Theodore W Randolph
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO, 80303, USA.
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Seesala VS, Sheikh L, Basu B, Mukherjee S. Mechanical and Bioactive Properties of PMMA Bone Cement: A Review. ACS Biomater Sci Eng 2024; 10:5939-5959. [PMID: 39240690 DOI: 10.1021/acsbiomaterials.4c00779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2024]
Abstract
Over the past few decades, poly(methyl methacrylate) (PMMA) based bone cement has been clinically used extensively in orthopedics for arthroplasty and kyphoplasty, due to its biocompatibility and excellent primary fixation to the host bone. In this focused review, we discuss the use of various fillers and secondary chemical moieties to improve the bioactivity and the physicochemical properties. The viscosity of the PMMA blend formulations and working time are crucial to achieving intimate contact with the osseous tissue, which is highly sensitive to organic or inorganic fillers. Hydroxyapatite as a reinforcement resulted in compromised mechanical properties of the modified cement. The possible mechanisms of the additive- or filler-dependent strengthening or weakening of the PMMA blend are critically reviewed. The addition of layered double hydroxides with surface functionalization appears to be a promising approach to enhance the bonding of filler with the PMMA matrix. Such an approach consequently improves the mechanical properties, owing to enhanced dispersion as well as contributions from crack bridging. Finally, the use of emerging alternatives, such as nanoparticles, and the use of natural biomolecules were highlighted to improve bioactivity and antibacterial properties.
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Affiliation(s)
- Venkata Sundeep Seesala
- Advanced Materials and Characterization Group, Research and Development Division, Tata Steel Ltd, Jamshedpur 831001, India
| | - Lubna Sheikh
- Advanced Materials and Characterization Group, Research and Development Division, Tata Steel Ltd, Jamshedpur 831001, India
| | - Bikramjit Basu
- Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bengaluru 560012, India
| | - Subrata Mukherjee
- Advanced Materials and Characterization Group, Research and Development Division, Tata Steel Ltd, Jamshedpur 831001, India
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Babu PJ, Tirkey A, Paul AA, Kristollari K, Barman J, Panda K, Sinha N, Babu BR, Marks RS. Advances in nano silver-based biomaterials and their biomedical applications. ENGINEERED REGENERATION 2024; 5:326-341. [DOI: 10.1016/j.engreg.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Egger V, Dammerer D, Degenhart G, Pallua JD, Schmölz W, Thaler M, Kühn KD, Nogler M, Putzer D. Does the Addition of Low-Dose Antibiotics Compromise the Mechanical Properties of Polymethylmethacrylate (PMMA)? Polymers (Basel) 2024; 16:2378. [PMID: 39204597 PMCID: PMC11359730 DOI: 10.3390/polym16162378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024] Open
Abstract
The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement (BC) in medium- and high-viscosity versions were compared to unloaded BC using a vacuum mixing system. As an additional control group, manual mixed unloaded BC was used. In a uniaxial compression test, ultimate compressive strength, compressive yield strength, and compression modulus of elasticity, as well as ultimate and yield strain, were determined according to ISO 5833-2022 guidelines. All groups exceeded the minimum compressive strength (70 MPa) specified in the ISO 5833 guidelines. Both ALBC groups showed a similar ultimate compressive and yield strength to the unloaded BC. The results showed that vacuum mixing increased the compression strength of BC. ALBC showed similar compressive strength to their non-antibiotic counterparts when vacuum mixing was performed. Added low-dose gentamicin acted as a plasticizer on bone cement. From a biomechanical point of view, the usage of gentamicin-based ALBC formulations is viable.
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Affiliation(s)
- Valentina Egger
- Department of Orthopaedic and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (V.E.); (J.D.P.); (M.N.)
| | - Dietmar Dammerer
- Department for Orthopaedics and Traumatology, University Hospital Krems, 3500 Krems an der Donau, Austria;
- Department for Orthopedics and Traumatology, Karl Landsteiner University of Health Sciences, 3500 Krems an der Donau, Austria
| | - Gerald Degenhart
- Department for Radiology, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - Johannes D. Pallua
- Department of Orthopaedic and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (V.E.); (J.D.P.); (M.N.)
| | - Werner Schmölz
- Department of Orthopaedic and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (V.E.); (J.D.P.); (M.N.)
| | - Martin Thaler
- Helios Klinikum, Arthroplasty Center Munich West, 81241 Munich, Germany;
- Center of Orthopaedics, Trauma Surgery and Rehabilitation Medicine, University of Greifswald, 17489 Greifswald, Germany
| | - Klaus-Dieter Kühn
- Department for Orthopaedics and Traumatology, Medical University Graz, 8036 Graz, Austria;
| | - Michael Nogler
- Department of Orthopaedic and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (V.E.); (J.D.P.); (M.N.)
| | - David Putzer
- Department of Orthopaedic and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (V.E.); (J.D.P.); (M.N.)
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Naoum S, Koutserimpas C, Pantekidis I, Giovanoulis V, Veizi E, Piagkou M, Ioannou P, Samonis G, Domouchtsidou A, Tsantes AG, Papadopoulos DV. Antimicrobial Regimens in Cement Spacers for Periprosthetic Joint Infections: A Critical Review. Antibiotics (Basel) 2024; 13:772. [PMID: 39200072 PMCID: PMC11351621 DOI: 10.3390/antibiotics13080772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/11/2024] [Accepted: 08/13/2024] [Indexed: 09/01/2024] Open
Abstract
Antibiotic-loaded cement spacers (ALCSs) are essential for treating periprosthetic joint infections (PJIs) by providing mechanical support and local antibiotic delivery. The purpose of this review is to comprehensively examine the various types of spacers utilised in the management of periprosthetic joint infections (PJIs), including both static and articulating variants and to analyse the fundamental principles underlying spacer use, their clinical benefits, the selection and administration of antimicrobial agents, appropriate dosages, and potential adverse effects. Articulating spacers, which allow joint mobility, often yield better outcomes than static ones. Spacer pharmacokinetics are vital for maintaining therapeutic antibiotic levels, influenced by cement porosity, mixing techniques, and the contact area. Antibiotic choice depends on heat stability, solubility, and impact on cement's mechanical properties. Mechanical properties are crucial, as spacers must withstand physical stresses, with antibiotics potentially affecting these properties. Complications, such as tissue damage and systemic toxicity, are discussed, along with mitigation strategies. Future advancements include surface modifications and novel carriers to enhance biofilm management and infection control.
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Affiliation(s)
- Symeon Naoum
- Department of Trauma and Orthopaedics, Royal Berkshire Hospital, Reading RG1 5AN, UK;
| | - Christos Koutserimpas
- Orthopaedic Surgery and Sports Medicine Department, Croix-Rousse Hospital, University Hospital, 69317 Lyon, France
- Department of Anatomy, School of Medicine, Faculty of Health Sciences, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 11527 Athens, Greece;
| | - Ioannis Pantekidis
- Department of Trauma and Orthopaedics, Guy’s and St. Thomas’ NHS Foundation Trust, London SE1 7EH, UK
| | - Vasileios Giovanoulis
- Department of Orthopaedic Surgery, Hôpital Henri Mondor, AP-HP, Université Paris Est Créteil (UPEC), 94010 Creteil, France;
| | - Enejd Veizi
- Department of Orthopedics and Traumatology, Yıldırım Beyazıt University, Ankara City Hospital, Ankara 2367, Turkey;
| | - Maria Piagkou
- Department of Anatomy, School of Medicine, Faculty of Health Sciences, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 11527 Athens, Greece;
| | - Petros Ioannou
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.S.)
| | - George Samonis
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.S.)
- First Department of Medical Oncology, Metropolitan Hospital of Neon Faliron, 18547 Athens, Greece
| | - Aglaia Domouchtsidou
- Microbiology Department, “Saint Savvas” Oncology Hospital, 11522 Athens, Greece; (A.D.); (A.G.T.)
| | - Andreas G. Tsantes
- Microbiology Department, “Saint Savvas” Oncology Hospital, 11522 Athens, Greece; (A.D.); (A.G.T.)
- Laboratory of Hematology and Blood Bank Unit, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Dimitrios V. Papadopoulos
- 2nd Academic Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 14233 Athens, Greece;
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Lekkala S, Inverardi N, Yuh J, Wannomae KK, Tierney P, Sekar A, Muratoglu OK, Oral E. Antibiotic-Loaded Ultrahigh Molecular Weight Polyethylenes. Macromol Biosci 2024; 24:e2300389. [PMID: 38095273 PMCID: PMC11018474 DOI: 10.1002/mabi.202300389] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 11/20/2023] [Indexed: 01/09/2024]
Abstract
The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci.
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Affiliation(s)
- Sashank Lekkala
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Nicoletta Inverardi
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02114, USA
| | - Jean Yuh
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Keith K. Wannomae
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Peyton Tierney
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Amita Sekar
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02114, USA
| | - Orhun K. Muratoglu
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02114, USA
| | - Ebru Oral
- Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02114, USA
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10
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Sharma C, Verma M, Abidi SMS, Shukla AK, Acharya A. Functional fluorescent nanomaterials for the detection, diagnosis and control of bacterial infection and biofilm formation: Insight towards mechanistic aspects and advanced applications. Colloids Surf B Biointerfaces 2023; 232:113583. [PMID: 37844474 DOI: 10.1016/j.colsurfb.2023.113583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/20/2023] [Accepted: 10/06/2023] [Indexed: 10/18/2023]
Abstract
Infectious diseases resulting from the high pathogenic potential of several bacteria possesses a major threat to human health and safety. Traditional methods used for screening of these microorganisms face major issues with respect to detection time, selectivity and specificity which may delay treatment for critically ill patients past the optimal time. Thus, a convincing and essential need exists to upgrade the existing methodologies for the fast detection of bacteria. In this context, increasing number of newly emerging nanomaterials (NMs) have been discovered for their effective use and applications in the area of diagnosis in bacterial infections. Recently, functional fluorescent nanomaterials (FNMs) are extensively explored in the field of biomedical research, particularly in developing new diagnostic tools, nanosensors, specific imaging modalities and targeted drug delivery systems for bacterial infection. It is interesting to note that organic fluorophores and fluorescent proteins have played vital role for imaging and sensing technologies for long, however, off lately fluorescent nanomaterials are increasingly replacing these due to the latter's unprecedented fluorescence brightness, stability in the biological environment, high quantum yield along with high sensitivity due to enhanced surface property etc. Again, taking advantage of their photo-excitation property, these can also be used for either photothermal and photodynamic therapy to eradicate bacterial infection and biofilm formation. Here, in this review, we have paid particular attention on summarizing literature reports on FNMs which includes studies detailing fluorescence-based bacterial detection methodologies, antibacterial and antibiofilm applications of the same. It is expected that the present review will attract the attention of the researchers working in this field to develop new engineered FNMs for the comprehensive diagnosis and treatment of bacterial infection and biofilm formation.
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Affiliation(s)
- Chandni Sharma
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Mohini Verma
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Syed M S Abidi
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Ashish K Shukla
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Amitabha Acharya
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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11
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Chen N. Embedded 3D printing and pressurized thermo-curing of PMMA for medical implants. J Mech Behav Biomed Mater 2023; 146:106083. [PMID: 37678106 DOI: 10.1016/j.jmbbm.2023.106083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/15/2023] [Accepted: 08/20/2023] [Indexed: 09/09/2023]
Abstract
Poly (methyl methacrylate) (PMMA) is a synthetic polymer commonly used for medical implants in cranioplasty and orthopedic surgery owing to its excellent mechanical properties, optical transparency, and minimal inflammatory responses. Recently, the development of 3D printing opens new avenues in the fabrication of patient-specific PMMA implants for personalized medicine. However, challenges are confronted when adapting medical-grade PMMA to the 3D printing process due to its dynamic viscosity and nonself-supporting characteristics before cured. In addition, the intrinsically exothermic polymerization of MMA brings about bubble generation issues that reduce its mechanical performance harshly. Therefore, in this study, an embedded 3D printing methodology followed by pressurized thermo-curing is proposed and developed: a granular alginate microgel is designed for serving as a supporting matrix when jamming formed between the granules to structurally support the extruded precursor filaments of PMMA-MMA ink during both 3D printing and post-curing; moreover, the autoclave reactor enclosing the alginate matrix and as-sculpted PMMA structures is utilized to generate temperature-dependent pressure, which serves for suppressing the bubbles and solidifying the polymerized MMA during the post-curing process. The 3D printed PMMA is comparably matchable to traditional PMMA castings in terms of their microstructures, density, thermal properties, mechanical performance and biocompatibility. In the future, the proposed embedded 3D printing platform combined with the special post-curing method has great potential for a customized and cost-effective fabrication of patient-specific, complex and functional PMMA implants.
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Affiliation(s)
- Na Chen
- Xi'an Children's Hospital, Xi'an, Shaanxi, China.
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12
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Sharma P, Baghel A. Outcome of intramedullary nail coated with antibiotic-impregnated cement in chronic osteomyelitis. Ann Afr Med 2023; 22:434-439. [PMID: 38358142 PMCID: PMC10775937 DOI: 10.4103/aam.aam_185_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 02/16/2024] Open
Abstract
Introduction Chronic osteomyelitis (Chr OM) may result as a sequel of acute hematogenous infection or following open fractures or orthopedic surgeries. Among various osteoarticular infections, Chr OM is one of the most challenging in terms of treatment. In the present study, we evaluate the outcome of antibiotic cement-coated nails in the treatment of chronic pyogenic osteomyelitis and also discuss the future innovations in field of antibiotic-compatible biomaterials for coating the implants. Materials and Methods Twelve cases of Chr OM (5 hematogenous and 7 exogenous following trauma or surgery) were operated by intramedullary nail coated with antibiotic-impregnated bone cement from September 2018 to January 2021. All the cases had bacteriological confirmation of infection by deep curettage and its subsequent culture sensitivity. K nail was used in 10 cases and elastic stable intramedullary nails were used in 2 cases. Results Out of 12 cases, 8 were male and 4 were female. The average duration of follow-up was 13 months. Infection was controlled in all the cases (two cases required repeat antibiotic-coated nailing), and there was no incidence of relapse in any case. The control of infection was assessed by clinical assessment and laboratory parameters. Conclusion Antibiotic cement-coated nails are an effective method in local control of infection in Chr OM without any systemic side effect.
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Affiliation(s)
- Pulak Sharma
- Department of Orthopaedics, Apex Trauma Center, SGPGI, Lucknow, Uttar Pradesh, India
| | - Anurag Baghel
- Department of Orthopaedics, Apex Trauma Center, SGPGI, Lucknow, Uttar Pradesh, India
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13
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Hollyer I, Ivanov D, Kappagoda S, Lowenberg DW, Goodman SB, Amanatullah DF. Selecting a high-dose antibiotic-laden cement knee spacer. J Orthop Res 2023; 41:1383-1396. [PMID: 37127938 DOI: 10.1002/jor.25570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 04/17/2023] [Indexed: 05/03/2023]
Abstract
Prosthetic joint infection [PJI] after total knee arthroplasty (TKA) remains a common and challenging problem for joint replacement surgeons and patients. Once the diagnosis of PJI has been made, patient goals and characteristics as well as the infection timeline dictate treatment. Most commonly, this involves a two-stage procedure with the removal of all implants, debridement, and placement of a static or dynamic antibiotic spacer. Static spacers are commonly indicated for older, less healthy patients that would benefit from soft tissue rest after initial debridement. Mobile spacers are typically used in younger, healthier patients to improve quality of life and reduce soft-tissue contractures during antibiotic spacer treatment. Spacers are highly customizable with regard to antibiotic choice, cement variety, and spacer design, each with reported advantages, drawbacks, and indications that will be covered in this article. While no spacer is superior to any other, the modern arthroplasty surgeon must be familiar with the available modalities to optimize treatment for each patient. Here we propose a treatment algorithm to assist surgeons in deciding on treatment for PJI after TKA.
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Affiliation(s)
- Ian Hollyer
- Department of Orthopaedic Surgery, Stanford University, Redwood City, California, USA
| | - David Ivanov
- Department of Orthopaedic Surgery, Stanford University, Redwood City, California, USA
| | - Shanthi Kappagoda
- Division of Infectious Diseases and Geographic Medicine, Stanford Univeristy, Stanford, California, USA
| | - David W Lowenberg
- Department of Orthopaedic Surgery, Stanford University, Redwood City, California, USA
| | - Stuart B Goodman
- Department of Orthopaedic Surgery, Stanford University, Redwood City, California, USA
| | - Derek F Amanatullah
- Department of Orthopaedic Surgery, Stanford University, Redwood City, California, USA
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14
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Zhu K, Han S, Zhang Z, Wang C, Cui B, Chen Z. Efficacy of Antibiotic Cement in Preserving Endoplants After Infection With Plate Exposure. Surg Infect (Larchmt) 2023. [PMID: 37126412 DOI: 10.1089/sur.2022.382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023] Open
Abstract
Background: To study the feasibility and efficacy of antibiotic cement in preserving endoplants after infection in patients with early tibial plateau fracture on plate exposure. Patients and Methods: A retrospective analysis of 23 patients treated for post-operative infection with plate exposure after tibial plateau fracture between 2017 and 2021. They were divided into the observation group (10 patients) and the control group (13 patients). Total operation time, length of hospitalization, hospitalization cost, the number of surgeries, white blood cell (WBC) count, neutrophil (NEUT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the post-operative evaluation index, and complications were observed during the follow-up period. Results: All patients were followed up for 6 to 12 months; wound healing was observed in both groups. The total operation time for patients in the control group was longer compared with the observation group. However, the length of hospitalization, hospitalization cost, and number of surgeries in the observation group were less compared with the control group. No difference in WBC, NEUT, ESR, and CRP levels was observed one day after surgery. Furthermore, WBC, NEUT, ESR, and CRP levels were higher in patients in the control group compared with the observation group 72 hours after surgery. There were no differences in the post-operative evaluation index and complications in both groups. Conclusions: The antibiotic cement coating used for treating early post-operative infection in patients with tibial plateau fracture could effectively control infection while retaining endoplant, thereby promoting wound healing. It could also reduce pain and the medical burden on patients.
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Affiliation(s)
- Kun Zhu
- Department of Orthopaedic, The First Affiliated Hospital of Bengbu Medical College, BengBu, Anhui Province, China
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, BengBu, Anhui Province, China
- Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjin, Jiangsu Province, China
| | - Shaoyu Han
- Trauma Center, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China
| | - Zhenqing Zhang
- Trauma Center, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China
| | - Chuangong Wang
- Trauma Center, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China
| | - Bingjun Cui
- Trauma Center, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China
| | - Zhixiang Chen
- Trauma Center, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China
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15
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Han J, Zheng X, Liu J, Wang Y, Cui Z, Wu S, Liang Y, Zhu S, Ge X, Li Z. Modification and evaluation of diatrizoate sodium containing polymethyl methacrylate bone cement. J Biomater Appl 2023; 37:1300-1314. [PMID: 36607821 DOI: 10.1177/08853282221150359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Polymethyl methacrylate (PMMA) bone cement is now widely used in percutaneous vertebro plasty (PVP) and percutaneous kyphoplasty (PKP). However, studies showed that the radiopacifiers (zirconia, barium sulfate, etc.) added to PMMA will have a negative impact on its use, e.g. barium sulfate will weaken the mechanical properties of bone cement and lead to bone absorption and aseptic loosening. Iodine is an element existing in the human body and has good imaging performance. Iodine contrast agent has been used in clinic for many years and has abundant clinical data. Therefore, using iodine instead of barium sulfate may be a promising choice. In this paper, the effect of different content of diatrizoate sodium (DTA, C11H8I3N2NaO4) on the properties of PMMA was studied and compared with the traditional PMMA bone cement containing 30 wt% barium sulfate. The mechanical properties, setting properties, radiopacity, and biocompatibility of bone cement were evaluated. The compressive strength of PMMA bone cement with 20 wt% DTA can reach 76.38 MPa. DTA released from bone cement up to 14 days accounted for only 2.3% of its dosage. The water contact angle was 62.3°. The contrast of bone cement on X-ray film was comparable to that of bone cement containing 30 wt% barium. The hemolysis rate was lower than 4%, and there was no obvious hemolysis. PMMA with 20 wt% DTA can maintain the relative growth rate of MC3T3-E1 and L929 cells above 80%. The results show that adding 20 wt% DTA into PMMA can obtain good radiopacity while maintaining its mechanical properties, setting properties, and biocompatibility. DTA can be used as a promising candidate material for PMMA bone cement radiopacifier.
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Affiliation(s)
- Jintong Han
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Xiaoqiang Zheng
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Jingyu Liu
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Yifan Wang
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Zhenduo Cui
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Shuilin Wu
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Yanqin Liang
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Shengli Zhu
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
| | - Xiang Ge
- Key Laboratory of Mechanism Theory and Equipment Design of Ministry of Education, School of Mechanical Engineering, 530428Tianjin University, Tianjin, China
| | - Zhaoyang Li
- Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, 530428Tianjin University, Tianjin, China
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16
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Ali AM, Abdallah MM. Study of Phenotypic and Genotypic Factors of Staphylococcus aureus Clinical Local Isolates. AL-MUSTANSIRIYAH JOURNAL OF SCIENCE 2022. [DOI: 10.23851/mjs.v33i4.1166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The isolates of Staphylococcus aureus were isolated from patients with various infections in hospitals, the isolates were identified and accurately diagnosed by phenotypic examination and biochemical tests, as well Vitek-2, and then genetic detection and diagnosis of many of the pathogenic factors associated with Staphylococcus aureus using conventional polymerase chain reaction (PCR) and testing for association by antibiotic resistance and production of some toxins by Staphylococcus aureus. After performing analysis of statistical, it was set up that the correlation coefficient of the PCR technique using virulence genes, sensitivity test to antibiotics and other virulence factors were significant at p < 0.05, but was insignificant with the biofilm production.
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17
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Xie H, Liu Y, An H, Yi J, Li C, Wang X, Chai W. Recent advances in prevention, detection and treatment in prosthetic joint infections of bioactive materials. Front Bioeng Biotechnol 2022; 10:1053399. [PMID: 36440438 PMCID: PMC9685530 DOI: 10.3389/fbioe.2022.1053399] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 10/31/2022] [Indexed: 11/07/2023] Open
Abstract
Prosthetic joint infection (PJI) is often considered as one of the most common but catastrophic complications after artificial joint replacement, which can lead to surgical failure, revision, amputation and even death. It has become a worldwide problem and brings great challenges to public health systems. A small amount of microbe attaches to the graft and forms a biofilm on its surface, which lead to the PJI. The current standard methods of treating PJI have limitations, but according to recent reports, bioactive materials have potential research value as a bioactive substance that can have a wide range of applications in the field of PJI. These include the addition of bioactive materials to bone cement, the use of antibacterial and anti-fouling materials for prosthetic coatings, the use of active materials such as bioactive glasses, protamine, hydrogels for prophylaxis and detection with PH sensors and fluorescent-labelled nanoparticles, and the use of antibiotic hydrogels and targeting delivery vehicles for therapeutic purposes. This review focus on prevention, detection and treatment in joint infections with bioactive materials and provide thoughts and ideas for their future applications.
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Affiliation(s)
- Hongbin Xie
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
| | - Yubo Liu
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
| | - Haoming An
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
| | - Jiafeng Yi
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
| | - Chao Li
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
| | - Xing Wang
- Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Wei Chai
- Senior Department of Orthopedics, Fourth Medical Center of People’s Liberation Army General Hospital, Beijing, China
- National Clinical Research Center for Orthopaedics, Sports Medicine & Rehabilitation, Beijing, China
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18
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Judd H, Benito J, Pannu TS, Villa JM, Higuera CA, Corces A. Nephrotoxicity Related to Antibiotic-Loaded Spacers in a 2-Stage Revision for Periprosthetic Joint Infection. Orthopedics 2022; 46:e136-e142. [PMID: 35876777 DOI: 10.3928/01477447-20220719-07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Antibiotic-loaded bone cement (ALBC) spacers are the mainstay in 2-stage revision, but antibiotics (vancomycin plus aminoglycosides) may undergo systemic absorption, resulting in acute kidney injury (AKI). Data on spacer antibiotics are heterogeneous. Our objective was to review risk factors for AKI and dosage of antibiotics. Significant AKI risk factors were antibiotic concentration greater than 3 or 3.6 g per cement batch, comorbidities, chronic kidney disease, and hypovolemia. Despite similar spacer antibiotic dosing, there was remarkable variability in serum concentrations. To err on the side of caution, it appears that antibiotic dose below 3 g per cement batch might be relatively safe until more evidence surfaces. Consideration of risk factors for AKI calls for appropriate antibiotic use in 2-stage revision. [Orthopedics. 20XX;XX(X):xx-xx.].
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19
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Maruo A, Oda T, Mineo R, Miya H, Muratsu H, Fukui T, Oe K, Kuroda R, Niikura T. Continuous local antibiotic perfusion: A treatment strategy that allows implant retention in fracture-related infections. J Orthop Surg (Hong Kong) 2022; 30:10225536221111902. [PMID: 35765727 DOI: 10.1177/10225536221111902] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
PURPOSE Fracture-related infections are difficult to treat because of the formation of biofilms around implants. Systemic antibiotics are notoriously ineffective against biofilms due to their insufficient penetration of tissues with poor vascularity. The goal of treating fracture-related infections is to achieve bone union while retaining the implant. Our proposal of continuous local antibiotic perfusion is a sustained local delivery system of sufficient antibiotics to bone and soft tissue infection sites, including to bone marrow via needles as intra-medullary antibiotics perfusion and to soft-tissue via double-lumen subcutaneous tubes as intra-soft tissue perfusion. METHODS In this study, we examined the outcomes of 40 patients treated for fracture-related infections using continuous local antibiotic perfusion between 2015 and 2021 at Steel Memorial Hirohata Hospital, Himeji, Japan. RESULT The antibiotic used for continuous local antibiotic perfusion was gentamicin in all cases. Implant removal was required in five patients. Two patients required toe amputation and knee arthrodesis, while the remaining 38 patients achieved fracture union. Only one case of transient acute renal injury as a systemic side effect was observed, but it soon resolved. The blood concentration of gentamicin could be adjusted to less than the trough level. CONCLUSIONS Continuous local antibiotic perfusion is a novel local drug delivery system that has the potential of delivering sufficient concentrations of antibiotics with few systemic side effects; it is a useful option for the treatment of fracture-related infections.
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Affiliation(s)
- Akihiro Maruo
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Takahiro Oda
- Department of Orthopaedic Surgery, 13705Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan
| | - Ryowa Mineo
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Hidetoshi Miya
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Hirotsugu Muratsu
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Tomoaki Fukui
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keisuke Oe
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
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20
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Antibiotic Cement Utilization for the Prophylaxis and Treatment of Infections in Spine Surgery: Basic Science Principles and Rationale for Clinical Use. J Clin Med 2022; 11:jcm11123481. [PMID: 35743551 PMCID: PMC9224689 DOI: 10.3390/jcm11123481] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/11/2022] [Accepted: 06/14/2022] [Indexed: 01/27/2023] Open
Abstract
Antibiotic bone cement (ABC) is an effective tool for the prophylaxis and treatment of osteomyelitis due to the controlled, sustained release of local antibiotics. ABC has been proven to be effective in the orthopedic fields of arthroplasty and extremity trauma, but the adoption of ABC in spine surgery is limited. The characteristics of ABC make it an optimal solution for treating vertebral osteomyelitis (VO), a serious complication following spine surgery, typically caused by bacterial and sometimes fungal and parasitic pathogens. VO can be devastating, as infection can result in pathogenic biofilms on instrumentation that is dangerous to remove. New techniques, such as kyphoplasty and novel vertebroplasty methods, could amplify the potential of ABC in spine surgery. However, caution should be exercised when using ABC as there is some evidence of toxicity to patients and surgeons, antibiotic allergies, bone cement structural impairment, and possible development of antibiotic resistance. The purpose of this article is to describe the basic science of antibiotic cement utilization and review its usage in spine surgery.
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21
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Al Maruf DSA, Parthasarathi K, Cheng K, Mukherjee P, McKenzie DR, Crook JM, Wallace GG, Clark JR. Current and future perspectives on biomaterials for segmental mandibular defect repair. INT J POLYM MATER PO 2022. [DOI: 10.1080/00914037.2022.2052729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- D S Abdullah Al Maruf
- Craniomaxillofacial Prosthetic and Advanced Reconstructive Translational Surgery, Chris O’Brien Lifehouse, Camperdown, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
| | - Krishnan Parthasarathi
- Craniomaxillofacial Prosthetic and Advanced Reconstructive Translational Surgery, Chris O’Brien Lifehouse, Camperdown, Australia
| | - Kai Cheng
- Craniomaxillofacial Prosthetic and Advanced Reconstructive Translational Surgery, Chris O’Brien Lifehouse, Camperdown, Australia
- The Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Camperdown, Australia
| | - Payal Mukherjee
- Craniomaxillofacial Prosthetic and Advanced Reconstructive Translational Surgery, Chris O’Brien Lifehouse, Camperdown, Australia
- The Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Camperdown, Australia
| | - David R. McKenzie
- Biomedical Innovation, Chris O’Brien Lifehouse, Camperdown, Australia
- School of Physics, Faculty of Science, The University of Sydney, Camperdown, Australia
| | - Jeremy M. Crook
- Biomedical Innovation, Chris O’Brien Lifehouse, Camperdown, Australia
- Sarcoma and Surgical Research Centre, Chris O’Brien Lifehouse, Camperdown, Australia
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, The University of Wollongong, Wollongong, Australia
- Illawarrah Health and Medical Research Institute, The University of Wollongong, Wollongong, Australia
| | - Gordon G. Wallace
- ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, The University of Wollongong, Wollongong, Australia
| | - Jonathan R. Clark
- Craniomaxillofacial Prosthetic and Advanced Reconstructive Translational Surgery, Chris O’Brien Lifehouse, Camperdown, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- The Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Camperdown, Australia
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22
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Crego-Vita D, Aedo-Martín D, Garcia-Cañas R, Espigares-Correa A, Sánchez-Pérez C, Berberich CE. Periprosthetic joint infections in femoral neck fracture patients treated with hemiarthroplasty – should we use antibiotic-loaded bone cement? World J Orthop 2022; 13:150-159. [PMID: 35317403 PMCID: PMC8891664 DOI: 10.5312/wjo.v13.i2.150] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/16/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hemiarthroplasty is the most common treatment in elderly patients with displaced intra-capsular femoral neck fracture (FNF). Prosthetic joint infection (PJI) is one of the most feared and frequent complications post-surgery because of the frail health status of these patients and the need for fast track surgery. Therefore, priorities should lie in effective preventive strategies to mitigate this burden.
AIM To determine how much the implementation of the routine use of antibiotic-loaded bone cement (ALBC) as a relatively easy-to-apply amendment to the surgical practice reduces the infection rate in our hemiarthroplasty cohort.
METHODS We retrospectively assessed all demographic, health status and treatment-related data of our FNF patients undergoing cemented hemiarthroplasty in the period from 2011 to 2017; 241 patients were further analyzed after exclusion of patients with cancer-related sequelae and those who died before the end of the 1-year observation period. The PJI rate as diagnosed on basis of the Musculoskeletal Infection Society (MSIS) criteria 2011 was determined for each included patient and compared in function of the bone cement used for hip stem fixation. Patients were split into a group receiving a plain bone cement in the period from January 2011 to June 2013 (non-ALBC group) and into a group receiving an ALBC in the period July 2013 to December 2017 (ALBC group). Data analysis was performed with statistical software. We further calculated the cost-efficacy of the implementation of routine use of ALBC in the second group balancing the in-hospital infection related treatment costs with the extra costs of use of ALBC.
RESULTS In total 241 FNF patients who received cemented hemiarthroplasty in the period from January 2011 to January 2017 were eligible for inclusion in this retrospective study. There were 8 PJI cases identified in the ALBC group among n = 94 patients, whereas 28 PJI cases were observed in the non-ALBC group among n = 147 patients. The statistical analysis showed an infection risk reduction of 55.3% (in particular due to the avoidance of chronic delayed infections) in the ALBC group (95%CI: 6.2%-78.7%; P = 0.0025). The cost-evaluation analysis demonstrated a considerable cost saving of 3.500 € per patient, related to the implementation of routine use of ALBC in this group.
CONCLUSION Use of ALBC is a potent infection preventive factor in FNF patients receiving cemented hemiarthroplasties. It was further found to be highly cost-effective.
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Affiliation(s)
- Diana Crego-Vita
- Department of Orthopaedic and Trauma Surgery, Hospital Central de la Defensa Gómez Ulla, Madrid 28047, Spain
| | - Daniel Aedo-Martín
- Department of Orthopaedic and Trauma Surgery, Hospital Universitario del Henares, Universidad Francisco de Vitoria, Coslada 28822, Madrid, Spain
| | - Rafael Garcia-Cañas
- Department of Orthopaedic and Trauma Surgery, Hospital Central de la Defensa Gómez Ulla, Madrid 28047, Spain
| | - Andrea Espigares-Correa
- Department of Orthopeadic and Trauma Surgery, Hospital Central de la Defensa Gómez Ulla, Madrid 28047, Spain
| | - Coral Sánchez-Pérez
- Department of Orthopeadic and Trauma Surgery, General University Hospital Gregorio Maranon, Madrid 28007, Spain
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Dong Z, Wu D, Engqvist H, Luo J, Persson C. Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate - A simple way of producing bioactive and drug-loadable composites for biomedical applications. Int J Biol Macromol 2021; 193:433-440. [PMID: 34715202 DOI: 10.1016/j.ijbiomac.2021.10.160] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 12/29/2022]
Abstract
Silk fibroin (SF) hydrogels have attracted extensive interest in biomedical applications due to their biocompatibility and wide availability. However, their generally poor mechanical properties limit their utility. Here, injectable, ready-to-use SF-based composites, simultaneously induced and reinforced by acidic calcium phosphates, were prepared via a dual-paste system requiring no complex chemical/physical treatment. The composite was formed by mixing a monocalcium phosphate monohydrate paste with a β-tricalcium phosphate/SF paste. The conformational transition of SF in an acidic environment forms continuous networks, and the acidic calcium phosphate, brushite and monetite, formed simultaneously in the networks during mixing. The composites displayed a partly elastomeric compression behavior, with mechanical properties increasing with an increasing calcium phosphate and β-sheet content at the lower calcium phosphate contents evaluated (22.2-36.4 wt%). While the stiffness was still relatively low, the materials presented a high elasticity and ductility, and no failure at stresses in the range of failure stresses of trabecular bone. Furthermore, the calcium phosphate confers bioactivity to the material, and the composites with a promising in vitro cell response also showed potential as drug vehicles, using vancomycin as a model drug. These dual-paste systems exhibit potential utility in biomedical applications, such as bone void fillers and drug vehicles.
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Affiliation(s)
- Zhiyun Dong
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Dan Wu
- Division of Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, Uppsala, Box 534, 751 21, Sweden
| | - Håkan Engqvist
- Division of Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, Uppsala, Box 534, 751 21, Sweden
| | - Jun Luo
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; Division of Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, Uppsala, Box 534, 751 21, Sweden.
| | - Cecilia Persson
- Division of Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, Uppsala, Box 534, 751 21, Sweden; Division of Biomedical Engineering, Department of Materials Science and Engineering, Uppsala University, Uppsala, Box 534, 751 21, Sweden.
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Feng F, Chen M, Wang X, Zhang H, Nie H, Tang H. Translation of a spinal bone cement product from bench to bedside. Bioact Mater 2021; 10:345-354. [PMID: 34901551 PMCID: PMC8636668 DOI: 10.1016/j.bioactmat.2021.08.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/01/2021] [Accepted: 08/09/2021] [Indexed: 01/18/2023] Open
Abstract
Spinal acrylic bone cements (ABCs) are used clinically for percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) to treat osteoporotic vertebral compression fractures. Product translation of spinal ABC products followed the design control processes including design verification and validation. The bench to bedside translation of the first Chinese spinal ABC product (Alliment®, namely Alliment Cement) approved by National Medical Products Administration of China was investigated and another commercial product served as the control (Osteopal®V, namely Osteopal V Cement). Results of non-clinical bench performance verification tests of compression, bending and monomer release showed that the newly marketed Alliment Cement is similar to the Osteopal V Cement with properties of both meeting the criteria specified by standards. The Alliment Cement demonstrated good biocompatibility during the 26 weeks’ bone implantation test. Porcine cadaver validation tests further revealed that the Alliment Cement satisfied the needs for both PVP and PKP procedures. A post-approval, retrospective clinical investigation further demonstrated the safety and efficacy of the Alliment Cement, with a significant reduction of pain and the improved stability of the fractured vertebral bodies. A successful translation of biomaterial medical products needs close collaborations among academia, industry, healthcare professionals and regulatory agencies.
Bench-to-bedside research of the first Chinese spinal acrylic bone cement product. •Pre- & clinical investigations demonstrate the product's safety and efficacy. •Translation of biomaterial medical products follows regulated processes.
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Affiliation(s)
- Fei Feng
- Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong An Rd, Xi Cheng District, Beijing, 100050, China
| | - Mengmeng Chen
- Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong An Rd, Xi Cheng District, Beijing, 100050, China
| | - Xuan Wang
- Beijing Bonsci Technology Co Ltd, No.100, 6th Kechuang Street, Beijing Economic and Technological Development Area, Beijing, 100176, China
| | - Hongwei Zhang
- Beijing Bonsci Technology Co Ltd, No.100, 6th Kechuang Street, Beijing Economic and Technological Development Area, Beijing, 100176, China
| | - Hongtao Nie
- Beijing Bonsci Technology Co Ltd, No.100, 6th Kechuang Street, Beijing Economic and Technological Development Area, Beijing, 100176, China
| | - Hai Tang
- Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong An Rd, Xi Cheng District, Beijing, 100050, China
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Slavnic D, Tong D, Anton G, Bashiti R, Carr D, Hanson C, Lytle E, Richards B, Soo TM. Efficacy and safety with the use of Antibiotic-impregnated Poly-methyl methacrylate (AI-PMMA) for thoracolumbar spinal reconstruction in pyogenic Spondylodiscitis: Retrospective cohort study. INTERDISCIPLINARY NEUROSURGERY 2021. [DOI: 10.1016/j.inat.2021.101324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Maruo A, Oda T, Miya H, Muratsu H, Fukui T, Oe K, Kuroda R, Niikura T. Intra-medullary antibiotics perfusion (iMAP) for the control of fracture-related infection early after osteosynthesis. J Orthop Surg (Hong Kong) 2021; 29:23094990211051492. [PMID: 34654344 DOI: 10.1177/23094990211051492] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
PURPOSE In our hospital, cases of bone and soft tissue infections have been treated with continuous local antibiotics perfusion that allows for continuous circulation of antibiotics throughout the infected lesion. We termed this treatment "intramedullary antibiotics perfusion (iMAP)" for bone infection such as fracture-related infection (FRI) and "intrasoft tissue antibiotics perfusion" for soft tissue infection. Many cases are treated with both modalities. To introduce iMAP, this study focused on the patients with FRI treated with iMAP and reviewed their treatment outcomes. METHODS We included 10 patients with FRI treated with iMAP between 2004 and 2017. The iMAP needles were inserted near the infected lesion, and an aminoglycoside antimicrobial was continuously administered. Patient characteristics, pathogenic bacteria, administered antibiotics, duration of administration, concentrations of antibiotics in blood and leachate fluid, fracture union rate, implant retention rate, and complications were studied. RESULTS The mean age of patients was 59.9 years, and the mean follow-up period was 2.5 years. Affected bones were the tibia (n = 8), humerus (n = 1), and fibula (n = 1). Deep infections developed on average 29.9 days after osteosynthesis. Pathogenic bacteria were methicillin-susceptible Staphylococcus aureus (n = 6), methicillin-resistant S. aureus (n = 2), and unknown (n = 2). Average iMAP duration was 17.1 days. In all patients, infection was eradicated while preserving the implants, and fracture union was achieved without complications. CONCLUSION iMAP is a novel local drug delivery system allowing high concentrations of antibiotics to be administered without complications and is useful in the treatment of FRI.
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Affiliation(s)
- Akihiro Maruo
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Takahiro Oda
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hidetoshi Miya
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Hirotsugu Muratsu
- Department of Orthopaedic Surgery, 38240Steel Memorial Hirohata Hospital, Himeji, Japan
| | - Tomoaki Fukui
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keisuke Oe
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, 538585Kobe University Graduate School of Medicine, Kobe, Japan
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Selvido DI, Bhattarai BP, Riddhabhaya A, Vongsawan K, Arunpraphan S, Wongsirichat N. A Review on the Application of Silver Nanoparticles in Oral and Maxillofacial Surgery. Eur J Dent 2021; 15:782-787. [PMID: 34428852 PMCID: PMC8630956 DOI: 10.1055/s-0041-1731589] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Silver nanoparticles (AgNPs) have been taken advantage of in dentistry because of their good antibacterial resistance and self-sustaining potential. However, in oral and maxillofacial surgery and implantology, there is a lesser amount of evidence. The few pieces of evidence need to be accentuated for possible amplification of its use in the dental setting. AgNPs in oral and maxillofacial surgery can be used in wound healing, bone healing, extractions, guided tissue regeneration, apical surgeries, oral cancer, and dental implants. This review aims to feature the utilization and application of AgNPs in oral and maxillofacial surgery and implant dentistry, emphasizing its need for potential future development in clinical settings.
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Affiliation(s)
| | | | - Apiwat Riddhabhaya
- International College of Dentistry, Walailak University, Bangkok, Thailand
| | - Kadkao Vongsawan
- International College of Dentistry, Walailak University, Bangkok, Thailand
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28
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Ludwick L, Chisari E, Wang J, Clarkson S, Collins L, Parvizi J. Emergence of Antibiotic Resistance Across Two-Stage Revision for Periprosthetic Joint Infection. J Arthroplasty 2021; 36:2946-2950. [PMID: 33934949 DOI: 10.1016/j.arth.2021.04.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/25/2021] [Accepted: 04/07/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND The current preferred treatment for chronic hip and knee periprosthetic joint infection (PJI) involves both surgical intervention and antibiotic treatment as part of a two-stage revision. The purpose of this study is to determine how often patients who underwent a two-stage revision for chronic PJI developed a subsequent antibiotic-resistant infection. METHODS We retrospectively reviewed the clinical records of 142 patients who underwent a two-stage revision for a chronic culture-positive PJI from January 2014 to May 2019. Demographic data and risk factors for PJI were identified. Resistance was defined in accordance with microbiology laboratory report and minimum inhibitory concentration. Statistical analysis consisted of descriptive statistics and univariate analysis. RESULTS Only 10 of the 142 patients (7.04%) demonstrated emergence of resistance to antibiotics across their two-stage revision. At reimplantation, 25 (17.6%) patients had positive cultures. Of these, 16 patients presented with a novel organism and 9 patients had positive culture for the same organism as the initial infection. During the entire course of the two-stage revision, including spacer exchanges and irrigation and debridement procedures, 15 (10.56%) patients demonstrated persistent infections, whereas 25 (17.6%) patients presented with novel infections. 26 (18.3%) patients had reinfection of the same joint within one year. CONCLUSION In the given cohort, there does not appear to be a major emergence of antibiotic resistant organisms in patients undergoing two-stage exchange arthroplasty and antibiotic treatment.
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Affiliation(s)
- Leanne Ludwick
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Emanuele Chisari
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Jasmine Wang
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Samuel Clarkson
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Lacee Collins
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Javad Parvizi
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
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29
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Hall TJ, Villapún VM, Addison O, Webber MA, Lowther M, Louth SET, Mountcastle SE, Brunet MY, Cox SC. A call for action to the biomaterial community to tackle antimicrobial resistance. Biomater Sci 2021; 8:4951-4974. [PMID: 32820747 DOI: 10.1039/d0bm01160f] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels. Microorganisms regularly and rapidly acquire resistance to antibiotic treatments and new drugs are continuously required. However, the inherent cost and risk to develop such molecules has resulted in a drying of the pipeline with very few compounds currently in development. Over the last two decades, efforts have been made to tackle the main sources of AMR. Nevertheless, these require the involvement of large governmental bodies, further increasing the complexity of the problem. As a group with a long innovation history, the biomaterials community is perfectly situated to push forward novel antimicrobial technologies to combat AMR. Although this involvement has been felt, it is necessary to ensure that the field offers a united front with special focus in areas that will facilitate the development and implementation of such systems. This paper reviews state of the art biomaterials strategies striving to limit AMR. Promising broad-spectrum antimicrobials and device modifications are showcased through two case studies for different applications, namely topical and implantables, demonstrating the potential for a highly efficacious physical and chemical approach. Finally, a critical review on barriers and limitations of these methods has been developed to provide a list of short and long-term focus areas in order to ensure the full potential of the biomaterials community is directed to helping tackle the AMR pandemic.
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Affiliation(s)
- Thomas J Hall
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Victor M Villapún
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Owen Addison
- Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, SE1 9RT, UK
| | - Mark A Webber
- Quadram Institute Bioscience, Norwich Research Park, Colney, NR4 7UQ, UK
| | - Morgan Lowther
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Sophie E T Louth
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Sophie E Mountcastle
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Mathieu Y Brunet
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
| | - Sophie C Cox
- School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
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30
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Lu CY, Church DC, Learn GD, Pokorski JK, von Recum HA. Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss. Macromol Biosci 2021; 21:e2000328. [PMID: 33885231 DOI: 10.1002/mabi.202000328] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 12/18/2020] [Indexed: 01/27/2023]
Abstract
Antibiotic-loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load-bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug-filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved. However, the mechanical strengths of PMMA is reduced. In order to decrease the mechanical loss, modified CD microparticles (PMMA-CD) are synthesized that contain covalently appended PMMA chains. The compressive strengths, handling characteristics, and refilling ability of PMMA cement with PMMA-CD are evaluated. Specifically, up to a 13.7% increase in compressive strength is observed when unmodified CD is substituted with PMMA-CD in PMMA samples with 10 wt% CD microparticles. Additionally, a 13.3% increase in working time, a 7.5% decrease in maximum polymerization temperature, and up to a 32.1% increase in amount of drug refilled are observed with the addition of 10 wt% CD PMMA-CD into PMMA in comparison to plain PMMA without CD microparticles.
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Affiliation(s)
- Chao-Yi Lu
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Derek C Church
- Department of NanoEngineering, University of California San Diego, Jacobs School of Engineering, La Jolla, CA, 92093, USA
| | - Greg D Learn
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Jonathan K Pokorski
- Department of NanoEngineering, University of California San Diego, Jacobs School of Engineering, La Jolla, CA, 92093, USA
| | - Horst A von Recum
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
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Shi A, Cai D, Hu J, Zhao X, Qin G, Han Y, Zhang E. Development of a low elastic modulus and antibacterial Ti-13Nb-13Zr-5Cu titanium alloy by microstructure controlling. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 126:112116. [PMID: 34082933 DOI: 10.1016/j.msec.2021.112116] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/06/2021] [Accepted: 04/14/2021] [Indexed: 11/28/2022]
Abstract
In order to prepare a titanium with a low elastic modulus and good antibacterial property to meet the requirements as a biomedical material, Ti-13Nb-13Zr-5Cu (TNZ-5Cu) alloy was prepared by high vacuum consume electric arc melting furnace and then subjected to a solution treatment at 950 °C followed by a short-term aging treatment at 600 °C, for 15 min, 30 min, 1 h and 2 h, respectively. The microstructure, mechanical property, antibacterial property and biocompatibility of TNZ-5Cu were investigated in detail. The research results have shown that the solid solution treated alloy was mainly composed of β-phase and α″-phase, while the aged alloys of β-phase, α″-phase, α-phase and Ti2Cu. Compared with Ti-13Nb-13Zr alloy (65 GPa) and Ti-6Al-4 V alloy (111 GPa), the elastic modulus of TNZ-5Cu alloy after solution treatment was about 72 GPa and increased with the aging treatment up to 85 GPa, and the hardness was maintained at a higher level than that of Ti-13Nb-13Zr alloys (288 HV). The bacteria plate count results showed that the antibacterial ability of TNZ-5Cu alloy increased with the extension of the aging duration from <60% at 15-30 min to >90% at 1-2 h. Cell experiments showed that all TNZ-5Cu alloy had good cell compatibility. The low modulus and the antibacterial property could provide potential to avoid stress shield and device-related inflection in the clinical application.
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Affiliation(s)
- Anqi Shi
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Diangeng Cai
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Jiali Hu
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Xiaotong Zhao
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Gaowu Qin
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China; Research Center for Metallic Wires, Northeastern University, Shenyang 110819, China
| | - Yong Han
- State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
| | - Erlin Zhang
- Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China; Research Center for Metallic Wires, Northeastern University, Shenyang 110819, China.
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Kaplan M, Özgür E, Ersoy O, Kehribar L, İdil N, Uzun L. Borate mineral loading into acrylic bone cements to gain cost-effectivity, enhanced antibacterial resistivity, and better cellular integration properties. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 32:980-993. [PMID: 33492195 DOI: 10.1080/09205063.2021.1880169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Polymethyl methacrylate (PMMA), called as bone cement, has been used in implant surgery, initially in dental practices, then in arthroplasty surgery for decades. Bone cement is a highly preferred chemical in the field of orthopedics due to its bone-like hardness and mechanical strength. Meanwhile, antibiotic-loaded cements are used in joints and similar surgeries are generally due to the risk of infection. In this study, we aimed to demonstrate the effects of borate mineral loading into bone cement on enhancing the antibacterial resistivity and cell integration as well as retaining mechanical properties. Moreover, the incorporation of minerals into bone cements makes them much more cost-friendly biomaterials for surgical operations. Herein, antibacterial properties were evaluated by using vancomycin- and gentamycin-susceptible strains of Enterococcus faecalis and Staphylococcus aureus whereas cell viability tests were performed by osteoblast cell lines. Three sets of the bone cements, plain, calcium borate-, and sodium borate-loaded, were prepared through commercial procedures and subjected to mechanical, antibacterial and cell viability tests. Percentage deformation determined by compression tests under 0.100 MPa pressure was determined in the range of 12.58%-10.67% in respect to the amount of sodium borate mineral loaded whereas that was determined in the range of 12.54%-9.87% in respect to the amount of calcium borate mineral loaded. Micro-CT results also supported good mineral integration and structural features of the composite bone cements. Furthermore, mineral incorporation enhanced the cell viability, in other words, cellular integrity, up to 101.28% for sodium borate-loaded (NB75, 7.5 g mineral) and 72.04% for calcium borate-loaded (CB75, 7.5 g mineral) bone cement according to the negative control group, fresh culture medium. As a conclusion, both of these minerals could be classified as promising alternatives for developing bone cements with better antibacterial resistivity and cellular integration properties.
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Affiliation(s)
- Mesut Kaplan
- Institute of Science, Division of Bioengineering, Hacettepe University, Ankara, Turkey
| | - Erdoğan Özgür
- Advanced Technologies Application and Research Center, Hacettepe University, Ankara, Turkey
| | - Orkun Ersoy
- Faculty of Engineering, Department of Geological Engineering, Hacettepe University, Ankara, Turkey
| | | | - Neslihan İdil
- Faculty of Science, Department of Biology, Hacettepe University, Ankara, Turkey
| | - Lokman Uzun
- Institute of Science, Division of Bioengineering, Hacettepe University, Ankara, Turkey.,Faculty of Science, Department of Chemistry, Hacettepe University, Ankara, Turkey
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Low-dose vancomycin-loaded cement spacer for two-stage revision of infected total hip arthroplasty. Jt Dis Relat Surg 2021; 31:449-455. [PMID: 32962574 PMCID: PMC7607947 DOI: 10.5606/ehc.2020.76108] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVES This study aims to evaluate the success rate in terms of eradication of infection and long-term outcomes of two- stage revision arthroplasty with spacers loaded with low-dose vancomycin alone for the treatment of an infected hip arthroplasty. PATIENTS AND METHODS The records of 42 two-stage exchange arthroplasty patients (16 males, 26 females; mean age 61 years; range, 30 to 80 years) treated between January 1999 and January 2009 were included in this retrospective study. In the first stage, following removal of the prosthesis and debridement, a spacer consisting of 1 g of vancomycin per 40 g of cement was placed in the infected joint space. Patients received six weeks of intravenous antibiotics according to intraoperative cultures. After cessation of systemic antibiotic treatment, with normal C-reactive protein and erythrocyte sedimentation rate levels, second stage surgery with cementless components was performed. RESULTS The mean follow-up duration was seven (range, 3 to 13) years. Two patients (4.7%) developed re-infection after two-stage reimplantation and one patient underwent a resection arthroplasty after repeated debridements. Five years of survival was 92.9% with Kaplan-Meier survival analysis. CONCLUSION For chronic infected total hip revisions, two-stage revision arthroplasty with low-dose vancomycin impregnated cement spacers have comparable re-infection and success rates. Low-dose vancomycin promotes effective infection control and reduces antibiotic toxicity.
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Cyphert EL, Zhang N, Marques DW, Learn GD, Zhang F, von Recum HA. Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue. J Funct Biomater 2021; 12:jfb12010008. [PMID: 33530542 PMCID: PMC7838923 DOI: 10.3390/jfb12010008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 12/21/2022] Open
Abstract
While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections. Previous work demonstrated efficacy of incorporating insoluble cyclodextrin (CD) microparticles into PMMA to improve antibiotic release and allow for post-implantation drug refilling to occur in a tissue-mimicking model. To simulate how antibiotic refilling may be possible in more physiologically relevant models, this work investigated development of bone and muscle refilling models. The bone refilling model involved embedding PMMA-CD into rabbit femur and administering antibiotic via intraosseous infusion. Muscle tissue refilling model involved implanting PMMA-CD beads in bovine muscle tissue and administering antibiotic via tissue injection. Duration of antimicrobial activity of refilled PMMA-CD was evaluated. PMMA-CD composite in bone and muscle tissue models was capable of being refilled with antibiotics and resulted in prolonged antimicrobial activity. PMMA-CD provided sustained and on-demand antimicrobial activity without removal of implant if infection develops. Intraosseous infusion appeared to be a viable technique to enable refilling of PMMA-CD after implantation in bone, reporting for the first time the ability to refill PMMA in bone.
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Sterility and Infection. Biomed Mater 2021. [DOI: 10.1007/978-3-030-49206-9_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Zapata MEV, Tovar CDG, Hernandez JHM. The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements. Biomolecules 2020; 10:E1616. [PMID: 33265973 PMCID: PMC7760599 DOI: 10.3390/biom10121616] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 11/20/2020] [Accepted: 11/24/2020] [Indexed: 02/08/2023] Open
Abstract
Acrylic bone cements (ABC) are widely used in orthopedics for joint fixation, antibiotic release, and bone defect filling, among others. However, most commercially available ABCs exhibit a lack of bioactivity and are susceptible to infection after implantation. These disadvantages generate long-term loosening of the prosthesis, high morbidity, and prolonged and expensive treatments. Due to the great importance of acrylic bone cements in orthopedics, the scientific community has advanced several efforts to develop bioactive ABCs with antibacterial activity through several strategies, including the use of biodegradable materials such as chitosan (CS) and nanostructures such as graphene oxide (GO), with promising results. This paper reviews several studies reporting advantages in bioactivity and antibacterial properties after incorporating CS and GO in bone cements. Detailed information on the possible mechanisms by which these fillers confer bioactive and antibacterial properties to cements, resulting in formulations with great potential for use in orthopedics, are also a focus in the manuscript. To the best of our knowledge, this is the first systematic review that presents the improvement in biological properties with CS and GO addition in cements that we believe will contribute to the biomedical field.
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Affiliation(s)
- Mayra Eliana Valencia Zapata
- Grupo de Materiales Compuestos, Escuela de Ingeniería de Materiales, Universidad del Valle, Calle 13 # 100-00, Cali 76001, Colombia;
| | - Carlos David Grande Tovar
- Grupo de Investigación de Fotoquímica y Fotobiología, Universidad del Atlántico, Carrera 30 Número 8-49, Puerto Colombia 081008, Colombia
| | - José Herminsul Mina Hernandez
- Grupo de Materiales Compuestos, Escuela de Ingeniería de Materiales, Universidad del Valle, Calle 13 # 100-00, Cali 76001, Colombia;
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Soleymani Eil Bakhtiari S, Bakhsheshi‐Rad HR, Karbasi S, Tavakoli M, Hassanzadeh Tabrizi SA, Ismail AF, Seifalian A, RamaKrishna S, Berto F. Poly(methyl methacrylate) bone cement, its rise, growth, downfall and future. POLYM INT 2020. [DOI: 10.1002/pi.6136] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Sanaz Soleymani Eil Bakhtiari
- Advanced Materials Research Center, Department of Materials Engineering Najafabad Branch, Islamic Azad University Najafabad Iran
| | - Hamid Reza Bakhsheshi‐Rad
- Advanced Materials Research Center, Department of Materials Engineering Najafabad Branch, Islamic Azad University Najafabad Iran
| | - Saeed Karbasi
- Biomaterials and Tissue Engineering Department, School of Advanced Technologies in Medicine Isfahan University of Medical Sciences Isfahan 81746‐73461 Iran
| | - Mohamadreza Tavakoli
- Department of Materials Engineering Isfahan University of Technology Isfahan 84156‐83111 Iran
| | - Sayed Ali Hassanzadeh Tabrizi
- Advanced Materials Research Center, Department of Materials Engineering Najafabad Branch, Islamic Azad University Najafabad Iran
| | - Ahmad Fauzi Ismail
- Advanced Membrane Technology Research Center (AMTEC) Universiti Teknologi Malaysia Skudai, Johor Bahru Johor 81310 Malaysia
| | - Alexander Seifalian
- Nanotechnology and Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd) London Biosciences Innovation Centre 2 Royal College Street London NW1 0NH U.K
| | - Seeram RamaKrishna
- Department of Mechanical Engineering National University of Singapore 9 Engineering Drive 1 Singapore 117576 Singapore
| | - Filippo Berto
- Department of Mechanical and Industrial Engineering Norwegian University of Science and Technology 7491 Trondheim Norway
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Wekwejt M, Michalska-Sionkowska M, Bartmański M, Nadolska M, Łukowicz K, Pałubicka A, Osyczka AM, Zieliński A. Influence of several biodegradable components added to pure and nanosilver-doped PMMA bone cements on its biological and mechanical properties. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 117:111286. [PMID: 32919647 DOI: 10.1016/j.msec.2020.111286] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 07/09/2020] [Accepted: 07/21/2020] [Indexed: 01/11/2023]
Abstract
Acrylic bone cements (BC) are wildly used in medicine. Despite favorable mechanical properties, processability and inject capability, BC lack bioactivity. To overcome this, we investigated the effects of selected biodegradable additives to create a partially-degradable BC and also we evaluated its combination with nanosilver (AgNp). We hypothesized that using above strategies it would be possible to obtain bioactive BC. The Cemex was used as the base material, modified at 2.5, 5 or 10 wt% with either cellulose, chitosan, magnesium, polydioxanone or tricalcium-phosphate. The resulted modified BC was examined for surface morphology, wettability, porosity, mechanical and nanomechanical properties and cytocompatibility. The composite BC doped with AgNp was also examined for its release and antibacterial properties. The results showed that it is possible to create modified cement and all studied modifiers increased its porosity. Applying the additives slightly decreased BC wettability and mechanical properties, but the positive effect of the additives was observed in nanomechanical research. The relatively poor cytocompatibility of modified BC was attributed to the unreacted monomer release, except for polydioxanone modification which increased cells viability. Furthermore, all additives facilitated AgNp release and increased BC antibacterial effectiveness. Our present studies suggest the optimal content of biodegradable component for BC is 5 wt%. At this content, an improvement in BC porosity is achieved without significant deterioration of BC physical and mechanical properties. Polydioxanone and cellulose seem to be the most promising additives that improve porosity and antibacterial properties of antibiotic or nanosilver-loaded BC. Partially-degradable BC may be a good strategy to improve their antibacterial effectiveness, but some caution is still required regarding their cytocompatibility. STATEMENT OF SIGNIFICANCE: The lack of bone cement bioactivity is the main limitation of its effectiveness in medicine. To overcome this, we have created composite cements with partially-degradable properties. We also modified these cements with nanosilver to provide antibacterial properties. We examined five various additives at three different contents to modify a selected bone cement. Our results broaden the knowledge about potential modifiers and properties of composite cements. We selected the optimal content and the most promising additives, and showed that the combination of these additives with nanosilver would increase cements` antibacterial effectiveness. Such modified cements may be a new solution for medical applications.
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Affiliation(s)
- M Wekwejt
- Biomaterials Division, Department of Materials Engineering and Bonding, Gdańsk University of Technology, Gdańsk, Poland.
| | - M Michalska-Sionkowska
- Faculty of Biological and Veterinary Sciences, Department of Environmental Microbiology and Biotechnology, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - M Bartmański
- Biomaterials Division, Department of Materials Engineering and Bonding, Gdańsk University of Technology, Gdańsk, Poland
| | - M Nadolska
- Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, Gdańsk, Poland
| | - K Łukowicz
- Institute of Zoology and Biomedical Research, Department of Biology and Cell Imaging, Faculty of Biology, Jagiellonian University, Kraków, Poland
| | - A Pałubicka
- Department of Surgical Oncologic, Medical University of Gdańsk, Gdańsk, Poland; Department of Laboratory Diagnostics and Microbiology with Blood Bank, Specialist Hospital in Kościerzyna, Kościerzyna, Poland
| | - A M Osyczka
- Institute of Zoology and Biomedical Research, Department of Biology and Cell Imaging, Faculty of Biology, Jagiellonian University, Kraków, Poland
| | - A Zieliński
- Biomaterials Division, Department of Materials Engineering and Bonding, Gdańsk University of Technology, Gdańsk, Poland
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Research into biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin antibiotics at common doses added to bone cement. Jt Dis Relat Surg 2020; 31:328-334. [PMID: 32584733 PMCID: PMC7489165 DOI: 10.5606/ehc.2020.74943] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/23/2020] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVES This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to polymethylmethacrylate (PMMA) in vitro. MATERIALS AND METHODS This prospective study was conducted between February 2016 and June 2016. Antibiotics were added to PMMA at doses frequently used in clinical practice. The antibiotic doses added were teicoplanin (2 g, 3 g, 4 g), gentamicin (0.5 g, 0.75 g, 1 g), daptomycin (0.5 g.) and vancomycin (2 g, 3 g, 4 g). Standard cement balls (10 mm) were created. Activated L929 mouse fibroblast cell culture was used for incubation. Agar diffusion, Cell Proliferation Kit II (XTT) test and electron microscope investigations were performed to examine biocompatibility and cytotoxicity. RESULTS In the cytotoxicity test, teicoplanin at 4 g and daptomycin at 0.5 g doses were observed to cause reductions in viability percentages. The same doses caused 20% and 20-40% cell lysis indices during the agar diffusion test. On electron microscope images, cytotoxic effects in fibroblast cells and involvement with the surface of cement balls were observed. CONCLUSION Gentamicin, vancomycin and teicoplanin were observed to be non-toxic and biocompatible at commonly-used dose intervals. Teicoplanin at 4 g and daptomycin at 0.5 g doses were identified to be cytotoxic and not biocompatible. When selecting antibiotics to be added to bone cement, care should be taken that the antibiotic is non-toxic and biocompatible.
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Pascoal DRC, Velozo ES, Braga MEM, Sousa HC, Cabral-Albuquerque ECM, Vieira de Melo SAB. Bioactive compounds of Copaifera sp. impregnated into three-dimensional gelatin dressings. Drug Deliv Transl Res 2020; 10:1537-1551. [PMID: 32557352 DOI: 10.1007/s13346-020-00797-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
This study investigates the immersion impregnation process of the copaiba oleoresin and leaf extract into SpongostanTM gelatin dressings to be used in wound healing treatment. Copaiba oleoresin and leaf extract were characterized by spectroscopic analyses in order to confirm the identity of bioactive compounds and their compatibility with dressing material. Their antibacterial properties were evaluated and oleoresin activity against Escherichia coli and Staphylococcus aureus bacteria was confirmed while the leaf extract showed activity against S. aureus. Solubility assays in organic solvents revealed that copaiba oleoresin is miscible into dichloromethane, while leaf extract showed a 20 g/ml solubility coefficient at 35 °C in the same solvent. These miscibility and solubility conditions were selected for the impregnation process. Using the organic solvent immersion method, 11 mg of copaiba oleoresin and 19 mg of leaf extract were impregnated into 1 cm3 of 3D matrix. The main bioactives from copaiba products, such as β-caryophyllene and lupeol, were tracked in the gelatin dressing. DSC and TGA assays showed no thermal changes in the samples after impregnation. Furthermore, the spatial organization of foam structure of the dressings was preserved after superficial distribution of oleoresin, as well as amorphous-like particulate deposition of leaf extract. The main compound of copaiba oleoresin, β-caryophyllene, which exhibits well-known anti-inflammatory activities, and the main compound of copaiba leaf extract, lupeol, also an anti-inflammatory agent, were successfully impregnated using organic solvent in wound dressings and are promising for further application on tissue wound healing. Graphical Abstract.
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Affiliation(s)
- Diego R C Pascoal
- Programa de Engenharia Industrial, Escola Politécnica, Universidade Federal da Bahia, Rua Aristides Novis, 2, 6° andar, Federação, Salvador, Bahia, 40210-630, Brazil
| | - Eudes S Velozo
- Departamento de Farmácia, Universidade Federal da Bahia, Rua Barão de Jeremoabo, s/n, Ondina, Salvador, Bahia, 40170-115, Brazil
| | - Mara E M Braga
- CIEPQPF, Department of Chemical Engineering, Universidade de Coimbra, Rua Sílvio Lima, Pólo II-Pinhal de Marrocos, 3030-790, Coimbra, Portugal
| | - Herminio C Sousa
- CIEPQPF, Department of Chemical Engineering, Universidade de Coimbra, Rua Sílvio Lima, Pólo II-Pinhal de Marrocos, 3030-790, Coimbra, Portugal
| | - Elaine C M Cabral-Albuquerque
- Programa de Engenharia Industrial, Escola Politécnica, Universidade Federal da Bahia, Rua Aristides Novis, 2, 6° andar, Federação, Salvador, Bahia, 40210-630, Brazil
| | - Silvio A B Vieira de Melo
- Programa de Engenharia Industrial, Escola Politécnica, Universidade Federal da Bahia, Rua Aristides Novis, 2, 6° andar, Federação, Salvador, Bahia, 40210-630, Brazil. .,Centro Interdisciplinar em Energia e Ambiente, Campus Universitário da Federação/Ondina, Universidade Federal da Bahia, Salvador, Bahia, 40170-115, Brazil.
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Kilinç S, Pazarci Ö, Keklikcioğlu Çakmak N, Taş A. Does the Addition of Poly(glycolide-co-lactide) to Teicoplanin-Containing Poly(methyl methacrylate) Beads Change the Elution Characteristics? Indian J Orthop 2020; 54:71-75. [PMID: 32952912 PMCID: PMC7474036 DOI: 10.1007/s43465-020-00116-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 04/10/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The objective of our study was to measure and compare the elution characteristics of teicoplanin from poly(methyl methacrylate) PMMA beads with those of poly(glycolide-co-lactide) PGLA-added beads. METHODS The study included two groups of PMMA + teicoplanin beads. PMMA was added to teicoplanin in Group 1 and PMMA + PGLA was added to teicoplanin in Group 2. A total of 16 beads of 1 cm3 were created for each group. Samples were added individually to tubes containing 3 ml of phosphate-buffered saline (PBS). Antibiotic elution was measured by measuring absorbance values of 1-ml samples taken at regular intervals using a UV-Vis spectrophotometer and cumulative percentages of drug release were calculated. In addition, the spectra of teicoplanin were identified using a FTIR spectrophotometer in a wavelength range of 400-4000 cm-1. RESULTS Drug elution in the PBS medium was measured and compared for Groups 1 and 2. The cumulative percentage of drug release from the PGLA-added beads (Group 2) was significantly higher (p = 0.01). The molecular structure of teicoplanin was also confirmed using FTIR. CONCLUSION The in vitro results showed that the addition of biodegradable PGLA into bone cement functions as a water-soluble porogen which allows for significant increases in the elution of teicoplanin from cement. This increase in elution suggests that the PGLA would allow for further fluid contact and exchange with the previously entrapped drug. These results may have important clinical applications.
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Affiliation(s)
- Seyran Kilinç
- Department of Orthopedics and Traumatology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Özhan Pazarci
- Department of Orthopedics and Traumatology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Neşe Keklikcioğlu Çakmak
- Department of Chemical Engineering, Faculty of Engineering, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Ayça Taş
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Sivas Cumhuriyet University, Sivas, Turkey
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Bao L, Li X, Qi Y, Wang Z, Li J. PEG/SBA-15-containing acrylic bone cement with enhanced drug release. Chem Eng Sci 2020. [DOI: 10.1016/j.ces.2019.115379] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Rajkhan AT, Esmat A, Alharthi SE. Protective Effect of Celastrol on Gentamicin-induced Nephrotoxicity in Mice. INT J PHARMACOL 2020. [DOI: 10.3923/ijp.2020.126.135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Cyphert EL, Lu CY, Marques DW, Learn GD, von Recum HA. Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling. Biomacromolecules 2019; 21:854-866. [DOI: 10.1021/acs.biomac.9b01523] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Erika L. Cyphert
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
| | - Chao-yi Lu
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
| | - Dylan W. Marques
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
| | - Greg D. Learn
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
| | - Horst A. von Recum
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
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Bistolfi A, Ferracini R, Albanese C, Vernè E, Miola M. PMMA-Based Bone Cements and the Problem of Joint Arthroplasty Infections: Status and New Perspectives. MATERIALS (BASEL, SWITZERLAND) 2019; 12:E4002. [PMID: 31810305 PMCID: PMC6926619 DOI: 10.3390/ma12234002] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 11/14/2019] [Accepted: 11/25/2019] [Indexed: 02/07/2023]
Abstract
Polymethyl methacrylate (PMMA)-based bone cement is a biomaterial that has been used over the last 50 years to stabilize hip and knee implants or as a bone filler. Although PMMA-based bone cement is widely used and allows a fast-primary fixation to the bone, it does not guarantee a mechanically and biologically stable interface with bone, and most of all it is prone to bacteria adhesion and infection development. In the 1970s, antibiotic-loaded bone cements were introduced to reduce the infection rate in arthroplasty; however, the efficiency of antibiotic-containing bone cement is still a debated issue. For these reasons, in recent years, the scientific community has investigated new approaches to impart antibacterial properties to PMMA bone cement. The aim of this review is to summarize the current status regarding antibiotic-loaded PMMA-based bone cements, fill the gap regarding the lack of data on antibacterial bone cement, and explore the progress of antibacterial bone cement formulations, focusing attention on the new perspectives. In particular, this review highlights the innovative study of composite bone cements containing inorganic antibacterial and bioactive phases, which are a fascinating alternative that can impart both osteointegration and antibacterial properties to PMMA-based bone cement.
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Affiliation(s)
- Alessandro Bistolfi
- AO Citta’ della Salute e della Scienza. CTO Hospital, Department of Orthopedics. Via Zuretti 29, 10126 Turin, Italy; (A.B.); (C.A.)
| | - Riccardo Ferracini
- IRCCS Ospedale Policlinico San Martino, Department of Surgical Sciences and Integrated Diagnostics, University of Genova, Largo R. Benzi 10, 16132 Genova, Italy;
| | - Carlo Albanese
- AO Citta’ della Salute e della Scienza. CTO Hospital, Department of Orthopedics. Via Zuretti 29, 10126 Turin, Italy; (A.B.); (C.A.)
| | - Enrica Vernè
- Department of Applied Science and Technology, PolitoBIOMed Lab, Politecnico di Torino, C.so Duca Degli Abruzzi 24, 10129 Torino, Italy;
| | - Marta Miola
- Department of Applied Science and Technology, PolitoBIOMed Lab, Politecnico di Torino, C.so Duca Degli Abruzzi 24, 10129 Torino, Italy;
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Silver Doping Mechanism in Bioceramics—From Ag+: Doped HAp to Ag°/BCP Nanocomposite. CRYSTALS 2019. [DOI: 10.3390/cryst9070326] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The results presented in this paper, based on the powder X-ray diffraction technique followed by Rietveld analyses, are devoted to the mechanism of silver incorporation in biphasic calcium phosphates. Results were confirmed by SEM observation. Samples were synthesized via the sol-gel route, followed by heat treatments. Two incorporation sites were highlighted: Ca2+ replacement by Ag+ into the calcium phosphates (HAp: hydroxyapatite and β-TCP: tricalcium phosphate), and the other as metallic silver Ag° nanoparticles (formed by autogenous reduction). The samples obtained were thus nanocomposites, written Ag°/BCP, composed of closely-mixed Ag° particles of about 100 nm at 400 °C (which became micrometric upon heating) and calcium phosphates, themselves substituted by Ag+ cations. Between 400 °C and 700 °C the cationic silver part was mainly located in the HAp phase of the composition Ca10-xAgx(PO4)6(OH)2-x (written Ag+: HAp). From 600 °C silver cations migrated to β-TCP to form the definite compound Ca10Ag(PO4)7 (written Ag+: TCP). Due to the melting point of Ag°, the doping element completely left our sample at temperatures above 1000 °C. In order to correctly understand the biological behavior of such material, which is potentially interesting for biomaterial applications, its complex doping mechanism should be taken into consideration for subsequent cytotoxic and bacteriologic studies.
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Valencia Zapata ME, Mina Hernandez JH, Grande Tovar CD, Valencia Llano CH, Diaz Escobar JA, Vázquez-Lasa B, San Román J, Rojo L. Novel Bioactive and Antibacterial Acrylic Bone Cement Nanocomposites Modified with Graphene Oxide and Chitosan. Int J Mol Sci 2019; 20:ijms20122938. [PMID: 31208091 PMCID: PMC6627441 DOI: 10.3390/ijms20122938] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/09/2019] [Accepted: 06/12/2019] [Indexed: 02/06/2023] Open
Abstract
Acrylic bone cements (ABCs) have played a key role in orthopedic surgery mainly in arthroplasties, but their use is increasingly extending to other applications, such as remodeling of cancerous bones, cranioplasties, and vertebroplasties. However, these materials present some limitations related to their inert behavior and the risk of infection after implantation, which leads to a lack of attachment and makes necessary new surgical interventions. In this research, the physicochemical, thermal, mechanical, and biological properties of ABCs modified with chitosan (CS) and graphene oxide (GO) were studied. Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) scanning electron microscopy (SEM), Raman mapping, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), compression resistance, mechanical dynamic analysis (DMA), hydrolytic degradation, cell viability, alkaline phosphatase (ALP) activity with human osteoblasts (HOb), and antibacterial activity against Gram-negative bacteria Escherichia coli were used to characterize the ABCs. The results revealed good dispersion of GO nanosheets in the ABCs. GO provided an increase in antibacterial activity, roughness, and flexural behavior, while CS generated porosity, increased the rate of degradation, and decreased compression properties. All ABCs were not cytotoxic and support good cell viability of HOb. The novel formulation of ABCs containing GO and CS simultaneously, increased the thermal stability, flexural modulus, antibacterial behavior, and osteogenic activity, which gives it a high potential for its uses in orthopedic applications.
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Affiliation(s)
- Mayra Eliana Valencia Zapata
- Grupo de Materiales Compuestos, Escuela de Ingeniería de Materiales, Universidad del Valle, Calle 13 # 100-00, Cali 76001, Colombia.
| | - José Herminsul Mina Hernandez
- Grupo de Materiales Compuestos, Escuela de Ingeniería de Materiales, Universidad del Valle, Calle 13 # 100-00, Cali 76001, Colombia.
| | - Carlos David Grande Tovar
- Grupo de Investigación de Fotoquímica y Fotobiología, Universidad del Atlántico, Carrera 30 Número 8-49, Puerto Colombia 081008, Colombia.
| | | | - José Alfredo Diaz Escobar
- Departamento de Ciencias Básicas, Institución Universitaria Antonio José Camacho, Avenida 6N # 28N - 102, Cali 76001, Colombia.
| | - Blanca Vázquez-Lasa
- Instituto de Ciencia y Tecnología de Polímeros, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain.
- Consorcio Centro de Investigación Biomedica en red, CIBER-BBN, 28029 Madrid, Spain.
| | - Julio San Román
- Instituto de Ciencia y Tecnología de Polímeros, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain.
- Consorcio Centro de Investigación Biomedica en red, CIBER-BBN, 28029 Madrid, Spain.
| | - Luis Rojo
- Instituto de Ciencia y Tecnología de Polímeros, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain.
- Consorcio Centro de Investigación Biomedica en red, CIBER-BBN, 28029 Madrid, Spain.
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Wright ZM, Pandit AM, Holt BD, Sydlik SA. Therapeutic Methacrylic Comonomers for Covalently Controlled Release from Mechanically Robust Bone Cement: Kinetics and Structure–Function Relationships. Macromolecules 2019. [DOI: 10.1021/acs.macromol.9b00368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Zoe M. Wright
- Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh Pennsylvania 15213 United States
| | - Avanti M. Pandit
- Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh Pennsylvania 15213 United States
| | - Brian D. Holt
- Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh Pennsylvania 15213 United States
| | - Stefanie A. Sydlik
- Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh Pennsylvania 15213 United States
- Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh Pennsylvania 15213, United States
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Surface degradation-enabled osseointegrative, angiogenic and antiinfective properties of magnesium-modified acrylic bone cement. J Orthop Translat 2019; 17:121-132. [PMID: 31194022 PMCID: PMC6551367 DOI: 10.1016/j.jot.2019.04.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/06/2019] [Accepted: 04/29/2019] [Indexed: 12/13/2022] Open
Abstract
Objective This work focuses on tackling the inadequate bone/implant interface strength of acrylic bone cements, which is a formidable problem diminishing their clinical performance, especially in percutaneous kyphoplasty surgery. Methods A new strategy of incorporating magnesium particles into clinically used poly(methylmethacrylate) (PMMA) bone cement to prepare a surface-degradable bone cement (SdBC) is proposed and validated both in vitro and in vivo. Results This surface degradation characteristic enables osseointegrative, angiogenic and antiinfective properties. SdBC showed fast surface degradation and formed porous surfaces as designed, while the desirable high compressive strengths (≥70 MPa) of the cement were preserved. Besides, the SdBC with proper Mg content promoted osteoblast adhesion, spreading, proliferation and endothelial cell angiogenesis capacity compared with PMMA. Also, SdBC demonstrated clear inhibitory effect on Staphylococcus aureus and Escherichia coli. In vivo evaluation on SdBC by the rat femur defect model showed that the bone/implant interface strength was significantly enhanced in SdBC (push-out force of 11.8 ± 1.5 N for SdBC vs 7.0 ± 2.3N for PMMA), suggesting significantly improved osseointegration and bone growth induced by the surface degradation of the cement. The injectability, setting times and compressive strengths of SdBC with proper content of Mg particles (2.8 wt% and 5.4 wt%) were comparable with those of the clinical acrylic bone cement, while the heat release during polymerization was reduced (maximum temperature 78 ± 1 °C for PMMA vs 73.3 ± 1.5 °C for SdBC). Conclusions This work validates a new concept of designing bioactive bone/implant interface in PMMA bone cement. And this surface-degradable bone cement possesses great potential for minimally invasive orthopaedic surgeries such as percutaneous kyphoplasty. The translational potential of this article This work reports PMMA/Mg surface-degradable acrylic bone cements that possess enhanced osseointegrative, angiogenic and antiinfective properties that are lacking in the clinically used acrylic bone cements. This new kind of bone cements could improve the treatment outcome of many orthopaedic surgeries such as percutaneous kyphoplasty and arthroplasty.
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Antibacterial and cytotoxic assessment of poly (methyl methacrylate) based hybrid nanocomposites. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 100:886-896. [PMID: 30948126 DOI: 10.1016/j.msec.2019.03.053] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 03/07/2019] [Accepted: 03/17/2019] [Indexed: 12/13/2022]
Abstract
Poly (methyl methacrylate) (PMMA) is an extensively used implant material in biomedical devices. Biofilm formation creates issues in PMMA-based biomedical implants, while emergence of drug resistant pathogens poses an additional complication. Hence development of surfaces that resist bacterial colonisation is extremely desirable. In this context, nanomaterials are among the potential choices. In the present work, nanocomposites (NCs) were developed by incorporation of chemically synthesized nanoparticles of CuO, cetyl trimethyl ammonium bromide (CTAB) capped CuO and ZnO (singly and in combination) in PMMA. The efficacy of these NCs was assessed against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria which are prevalent in many implant-associated infections. Results revealed species-specific response of the bacteria towards nanomaterials. CuO NC (0.1% (w/v)) was more effective against E. coli, while CTAB capped CuO NC and ZnO NC were very effective against S. aureus. Furthermore, combination of nanoparticles improved efficacy of nanocomposites against both the bacterial species. In vitro cytotoxicity assay using L6 myoblast cell line showed that all NCs at 0.1% (w/v) were biocompatible, showing >85% cell viability. The present study suggests that combination of NPs is a promising option to combat implant infection by multiple organisms.
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