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Shi Y, Wu X, Paydarfar JA, Halter RJ. An Imaging-Compatible Oral Retractor System for Transoral Robotic Surgery. Ann Biomed Eng 2024; 52:2473-2484. [PMID: 38796669 DOI: 10.1007/s10439-024-03536-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 05/02/2024] [Indexed: 05/28/2024]
Abstract
This study aimed to develop and validate a Computed Tomography (CT)/Magnetic Resonance Imaging (MRI)-compatible polymer oral retractor system to enable intraoperative image guidance for transoral robotic surgery (TORS). The retractor was designed based on standard-of-care metallic retractors and 3D (three-dimensional) printed with carbon fiber composite and nylon. The system was comprehensively evaluated in bench-top and cadaveric experiments in terms of its ability to enable intraoperative CT/MR images during TORS, functionality including surgical exposure and working volume, usability, compatibility with da Vinci surgical systems, feasibility for disinfection or sterilization, and robustness over an extended period of time. The polymer retractor system enabled the acquisition of high-resolution and artifact-free intraoperative CT/MR images during TORS. With an inter-incisive distance of 42.55 mm and a working volume of 200.09 cm3, it provided surgical exposure comparable to standard-of-care metallic retractors. The system proved intuitive and compatible with da Vinci S, Xi, and Single Port systems, enabling successful mock surgical tasks performed by surgeons and residents. The retractor components could be effectively disinfected or sterilized for clinical use without significant compromise in material strength, with STERRAD considered the optimal method. Throughout a 2 h mock procedure, the retractor system showed minimal displacements (<1.5 mm) due to surrounding tissue deformation, with insignificant device deformation. The 3D-printed polymer retractor system successfully enabled artifact-free intraoperative CT/MR imaging in TORS for the first time and demonstrated feasibility for clinical use. This breakthrough opens the door to surgical navigation with intraoperative image guidance in TORS, offering the potential to significantly improve surgical outcomes and patients' quality of life.
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Affiliation(s)
- Yuan Shi
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
| | - Xiaotian Wu
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
| | - Joseph A Paydarfar
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
- Section of Otolaryngology, Audiology, and Maxillofacial Surgery, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
- Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
| | - Ryan J Halter
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
- Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
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Wagner RK, Guarch-Pérez C, van Dam AP, Zaat SAJ, Kloen P. Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions. Strategies Trauma Limb Reconstr 2023; 18:73-81. [PMID: 37942437 PMCID: PMC10628616 DOI: 10.5005/jp-journals-10080-1586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 04/30/2023] [Indexed: 11/10/2023] Open
Abstract
Background Antibiotic-impregnated cement-coated plates (ACPs) have been used successfully for temporary internal fixation between stages in the two-stage treatment of infected non-unions. We describe our approach of using an ACP in the staged treatment of a methicillin-resistant Staphylococcus aureus (MRSA)-infected distal femoral non-union below a total hip prosthesis. In addition, we present the results of an in vitro experiment to provide an in-depth insight into the capacity of ACPs in (i) treating residual biofilm and (ii) preventing bacterial recolonisation. Materials and methods In the first stage, we used a titanium LISS plate coated with hand-mixed PALACOS with vancomycin (PAL-V) for temporary internal fixation combined with commercially prepared COPAL with gentamicin and vancomycin (COP-GV) to fill the segmental defect. In the second stage, the non-union was treated with double-plate fixation and bone grafting.A Kirby-Bauer agar disc diffusion assay was performed to determine the antimicrobial activity of both ACPs and a drug-release assay to measure antibiotic release over time. A biofilm killing assay was also carried out to determine if the antibiotic released was able to reduce or eradicate biofilm of the patient's MRSA strain. Results At one-year follow-up, there was complete bone-bridging across the previous non-union. The patient was pain-free and ambulatory without need for further surgery. Both ACPs with COP-GV and PAL-V exerted an antimicrobial effect against the MRSA strain with peak concentrations of antibiotic released within the first 24 hours. Concentrations released from COP-GV in the first 24 hours in vitro caused a 7.7-fold log reduction of colony-forming units (CFU) in the biofilm. At day 50, both COP-GV and PAL-V still released concentrations of antibiotic above the respective minimal inhibitory concentrations (MIC), likely contributing to the positive clinical outcome. Conclusion The use of an ACP provides stability and infection control in the clinical scenario of an infected non-union. This is confirmed in vitro where the release of antibiotics from ACPs is characterised by an early burst followed by a prolonged sustained release above the MIC until 50 days. The burst release from COP-GV reduces CFU in the biofilm and prevents early recolonisation through synergistic activity of the released vancomycin and gentamicin. Clinical significance An antibiotic-impregnated cement-coated plate is a useful addition to the surgeon's armamentarium to provide temporary internal fixation without the disadvantages of external fixation and contribute to infection control in an infected non-union. How to cite this article Wagner RK, Guarch-Pérez C, van Dam AP, et al. Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions. Strategies Trauma Limb Reconstr 2023;18(2):73-81.
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Affiliation(s)
- Robert Kaspar Wagner
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9; Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
| | - Clara Guarch-Pérez
- Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, The Netherlands
| | - Alje P van Dam
- Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, The Netherlands
| | - Sebastian AJ Zaat
- Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, The Netherlands
| | - Peter Kloen
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9; Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
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Bioengineering Approaches to Fight against Orthopedic Biomaterials Related-Infections. Int J Mol Sci 2022; 23:ijms231911658. [PMID: 36232956 PMCID: PMC9569980 DOI: 10.3390/ijms231911658] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 11/07/2022] Open
Abstract
One of the most serious complications following the implantation of orthopedic biomaterials is the development of infection. Orthopedic implant-related infections do not only entail clinical problems and patient suffering, but also cause a burden on healthcare care systems. Additionally, the ageing of the world population, in particular in developed countries, has led to an increase in the population above 60 years. This is a significantly vulnerable population segment insofar as biomaterials use is concerned. Implanted materials are highly susceptible to bacterial and fungal colonization and the consequent infection. These microorganisms are often opportunistic, taking advantage of the weakening of the body defenses at the implant surface–tissue interface to attach to tissues or implant surfaces, instigating biofilm formation and subsequent development of infection. The establishment of biofilm leads to tissue destruction, systemic dissemination of the pathogen, and dysfunction of the implant/bone joint, leading to implant failure. Moreover, the contaminated implant can be a reservoir for infection of the surrounding tissue where microorganisms are protected. Therefore, the biofilm increases the pathogenesis of infection since that structure offers protection against host defenses and antimicrobial therapies. Additionally, the rapid emergence of bacterial strains resistant to antibiotics prompted the development of new alternative approaches to prevent and control implant-related infections. Several concepts and approaches have been developed to obtain biomaterials endowed with anti-infective properties. In this review, several anti-infective strategies based on biomaterial engineering are described and discussed in terms of design and fabrication, mechanisms of action, benefits, and drawbacks for preventing and treating orthopaedic biomaterials-related infections.
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Combatting fungal biofilm formation by diffusive release of fluconazole from heptylamine plasma polymer coating. Biointerphases 2020; 15:061012. [PMID: 33339460 DOI: 10.1116/6.0000511] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
A drug-eluting coating applied onto biomedical devices and implants is an appropriate way to ensure that an inhibitory concentration of antimicrobial drugs is present at the device surface, thus preventing surface colonization and subsequent biofilm formation. In this study, a thin polymer coating was applied to materials, and it acted as a drug-delivery reservoir capable of surface delivery of the antifungal drug fluconazole to amounts up to 21 μg/cm2. The release kinetics into aqueous solution were quantified by UV spectroscopy and conformed to the Ritger-Peppas and Korsmeyer-Peppas model. Complementary microbiological assays were used to determine effectiveness against Candida albicans attachment and biofilm formation, and against the control heptylamine plasma polymer coating without drug loading, on which substantial fungal growth occurred. Fluconazole release led to marked antifungal activity in all assays, with log 1.6 reduction in CFUs/cm2. Cell viability assays and microscopy revealed that fungal cells attached to the fluconazole-loaded coating remained rounded and did not form hyphae and biofilm. Thus, in vitro screening results for fluconazole-releasing surface coatings showed efficacy in the prevention of the formation of Candida albicans biofilm.
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Bone ongrowth of a cementless silver oxide-containing hydroxyapatite-coated antibacterial acetabular socket. J Orthop Sci 2019; 24:658-662. [PMID: 30718042 DOI: 10.1016/j.jos.2018.12.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 11/05/2018] [Accepted: 12/20/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND The silver oxide-containing hydroxyapatite-coated socket (KYOCERA, Osaka, Japan) is a cementless antibacterial implant that has both the osteoconductivity of the HA and the antibacterial activity of silver. The silver oxide-containing hydroxyapatite coating was shown to have good osteoconductivity and new bone formation in vitro and in vivo. However, the histological bone ongrowth of this implant has not been proven in a clinical study. METHODS We analyzed bone ongrowth using two silver oxide-containing hydroxyapatite-coated sockets that were removed in revision total hip arthroplasty for recurrent dislocation. A histomorphometric analysis was performed using a scanning electron microscope (SEM) connected to a CCD camera and an elemental analysis was performed by energy-dispersive elemental spectrometry (EDS). RESULT A white structure thought to be osseous tissue was attached to the retrieved socket surface macroscopically, and histological bone ongrowth of the silver oxide-containing hydroxyapatite coating of the socket was confirmed by SEM. In addition, the presence of silver in the silver oxide-containing hydroxyapatite coating was confirmed in an elemental analysis by EDS. CONCLUSION Histologically, the silver oxide-containing hydroxyapatite-coated socket presented bone ongrowth in this clinical study.
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Querido MM, Aguiar L, Neves P, Pereira CC, Teixeira JP. Self-disinfecting surfaces and infection control. Colloids Surf B Biointerfaces 2019; 178:8-21. [PMID: 30822681 PMCID: PMC7127218 DOI: 10.1016/j.colsurfb.2019.02.009] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 02/04/2019] [Accepted: 02/05/2019] [Indexed: 12/27/2022]
Abstract
According to World Health Organization, every year in the European Union, 4 million patients acquire a healthcare associated infection. Even though some microorganisms represent no threat to healthy people, hospitals harbor different levels of immunocompetent individuals, namely patients receiving immunosuppressors, with previous infections, or those with extremes of age (young children and elderly), requiring the implementation of effective control measures. Public spaces have also been found an important source of infectious disease outbreaks due to poor or none infection control measures applied. In both places, surfaces play a major role on microorganisms' propagation, yet they are very often neglected, with very few guidelines about efficient cleaning measures and microbiological assessment available. To overcome surface contamination problems, new strategies are being designed to limit the microorganisms' ability to survive over surfaces and materials. Surface modification and/or functionalization to prevent contamination is a hot-topic of research and several different approaches have been developed lately. Surfaces with anti-adhesive properties, with incorporated antimicrobial substances or modified with biological active metals are some of the strategies recently proposed. This review intends to summarize the problems associated with contaminated surfaces and their importance on infection spreading, and to present some of the strategies developed to prevent this public health problem, namely some already being commercialized.
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Affiliation(s)
- Micaela Machado Querido
- National Institute of Health, Environmental Health Department, Porto, Portugal; EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
| | - Lívia Aguiar
- National Institute of Health, Environmental Health Department, Porto, Portugal
| | - Paula Neves
- National Institute of Health, Environmental Health Department, Porto, Portugal
| | - Cristiana Costa Pereira
- National Institute of Health, Environmental Health Department, Porto, Portugal; EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.
| | - João Paulo Teixeira
- National Institute of Health, Environmental Health Department, Porto, Portugal; EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
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Abstract
Limb salvage is widely practiced as standard of care in most cases of extremity bone sarcoma. Allograft and endoprosthesis reconstructions are the most widely utilized modalities for the reconstruction of large segment defects, however complication rates remain high. Aseptic loosening and infection remain the most common modes of failure. Implant integration, soft-tissue function, and infection prevention are crucial for implant longevity and function. Macro and micro alterations in implant design are reviewed in this manuscript. Tissue engineering principles using nanoparticles, cell-based, and biological augments have been utilized to develop implant coatings that improve osseointegration and decrease infection. Similar techniques have been used to improve the interaction between soft tissues and implants. Tissue engineered constructs (TEC) used in combination with, or in place of, traditional reconstructive techniques may represent the next major advancement in orthopaedic oncology reconstructive science, although preclinical results have yet to achieve durable translation to the bedside.
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Sjollema J, Zaat SAJ, Fontaine V, Ramstedt M, Luginbuehl R, Thevissen K, Li J, van der Mei HC, Busscher HJ. In vitro methods for the evaluation of antimicrobial surface designs. Acta Biomater 2018; 70:12-24. [PMID: 29432983 DOI: 10.1016/j.actbio.2018.02.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 01/12/2018] [Accepted: 02/01/2018] [Indexed: 11/16/2022]
Abstract
Bacterial adhesion and subsequent biofilm formation on biomedical implants and devices are a major cause of their failure. As systemic antibiotic treatment is often ineffective, there is an urgent need for antimicrobial biomaterials and coatings. The term "antimicrobial" can encompass different mechanisms of action (here termed "antimicrobial surface designs"), such as antimicrobial-releasing, contact-killing or non-adhesivity. Biomaterials equipped with antimicrobial surface designs based on different mechanisms of action require different in vitro evaluation methods. Available industrial standard evaluation tests do not address the specific mechanisms of different antimicrobial surface designs and have therefore been modified over the past years, adding to the myriad of methods available in the literature to evaluate antimicrobial surface designs. The aim of this review is to categorize fourteen presently available methods including industrial standard tests for the in vitro evaluation of antimicrobial surface designs according to their suitability with respect to their antimicrobial mechanism of action. There is no single method or industrial test that allows to distinguish antimicrobial designs according to all three mechanisms identified here. However, critical consideration of each method clearly relates the different methods to a specific mechanism of antimicrobial action. It is anticipated that use of the provided table with the fourteen methods will avoid the use of wrong methods for evaluating new antimicrobial designs and therewith facilitate translation of novel antimicrobial biomaterials and coatings to clinical use. The need for more and better updated industrial standard tests is emphasized. STATEMENT OF SIGNIFICANCE European COST-action TD1305, IPROMEDAI aims to provide better understanding of mechanisms of antimicrobial surface designs of biomaterial implants and devices. Current industrial evaluation standard tests do not sufficiently account for different, advanced antimicrobial surface designs, yet are urgently needed to obtain convincing in vitro data for approval of animal experiments and clinical trials. This review aims to provide an innovative and clear guide to choose appropriate evaluation methods for three distinctly different mechanisms of antimicrobial design: (1) antimicrobial-releasing, (2) contact-killing and (3) non-adhesivity. Use of antimicrobial evaluation methods and definition of industrial standard tests, tailored toward the antimicrobial mechanism of the design, as identified here, fulfill a missing link in the translation of novel antimicrobial surface designs to clinical use.
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Affiliation(s)
- Jelmer Sjollema
- University of Groningen, University Medical Center Groningen, Department of BioMedical Engineering, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
| | - Sebastian A J Zaat
- Department of Medical Microbiology, CINIMA (Center for Infection and Immunity Amsterdam), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
| | - Veronique Fontaine
- Unit of Pharmaceutical Microbiology and Hygiene, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Campus Plaine, Boulevard du Triomphe, 1050 Brussels, Belgium
| | | | - Reto Luginbuehl
- RMS Foundation, Bischmattstrasse 12, 2544 Bettlach, Switzerland
| | - Karin Thevissen
- Centre for Microbial and Plant Genetics, CMPG, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium
| | - Jiuyi Li
- School of Civil Engineering, Beijing Jiaotong University, 3 Shangyuancun, Xizhimenwai, Beijing 100044, China
| | - Henny C van der Mei
- University of Groningen, University Medical Center Groningen, Department of BioMedical Engineering, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
| | - Henk J Busscher
- University of Groningen, University Medical Center Groningen, Department of BioMedical Engineering, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
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Gou Y, Yang X, He L, Xu X, Liu Y, Liu Y, Gao Y, Huang Q, Liang K, Ding C, Li J, Zhao C, Li J. Bio-inspired peptide decorated dendrimers for a robust antibacterial coating on hydroxyapatite. Polym Chem 2017. [DOI: 10.1039/c7py00811b] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
SSP-PAMAM-NH2 inspired by the salivary statherin protein can tightly adsorb on the HA surface to achieve long-term antibacterial activity.
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Mullins ND, Deadman BJ, Moynihan HA, McCarthy FO, Lawrence SE, Thompson J, Maguire AR. The impact of storage conditions upon gentamicin coated antimicrobial implants. J Pharm Anal 2016; 6:374-381. [PMID: 29404006 PMCID: PMC5762933 DOI: 10.1016/j.jpha.2016.05.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 04/28/2016] [Accepted: 05/03/2016] [Indexed: 11/24/2022] Open
Abstract
A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography-mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.
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Affiliation(s)
- Nicholas D. Mullins
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
| | - Benjamin J. Deadman
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
| | - Humphrey A. Moynihan
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
| | - Florence O. McCarthy
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
| | - Simon E. Lawrence
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
| | | | - Anita R. Maguire
- Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
- School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College, Cork, Ireland
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Scoccianti G, Frenos F, Beltrami G, Campanacci DA, Capanna R. Levels of silver ions in body fluids and clinical results in silver-coated megaprostheses after tumour, trauma or failed arthroplasty. Injury 2016; 47 Suppl 4:S11-S16. [PMID: 27523624 DOI: 10.1016/j.injury.2016.07.042] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Infection in megaprostheses remains an unsolved problem, with a rate of occurrence ranging from 5% to 12%. Silver coating of medical devices has recently been proposed to reduce infection rate because of the antibacterial effect of silver. This innovation could be particularly interesting for megaprostheses, but few data have been reported in the literature. MATERIALS AND METHODS From June 2010 to August 2014 a modified MegaC System megaprosthesis with an innovative peripheral silver-added layer of titanium alloy ('Porag') was implanted in 33 patients after previous infection (21 patients) or at high risk for infection because of local or general conditions (12 patients). Previous infection followed megaprosthesis or standard arthroplasty procedures in 14 patients and trauma surgery in seven patients. A proximal femur replacement was performed in 13 patients, distal femur replacement in 13, total femur in one, and knee arthrodesis in six. Clinical results and levels of silver in blood, urine and wound drains were examined. RESULTS Minimum follow-up of the patients was one year (average 25.9 months). There was no infection during the first two years after surgery in the 12 patients who received a silver-coated megaprosthesis and had no previous history of infection. An infection developed in one patient at 25 months after surgery following two further surgical procedures. Infection recurred at seven months and 24 months in two out of the 21 patients (9.5%) who had received the implant because of previous septic complications. There was no clinical evidence of argyria, and no local or systemic side effects related to silver were detected. Mean levels of silver ranging from 0.41 to 5.33μg/L in blood and from 0.28 to 0.86μg/L in urine were detected at 24h to 36 months after surgery. CONCLUSIONS Silver-coated megaprostheses showed promising results in this series in terms of prevention of infection in a high-risk group of patients, many of whom had a history of infection. No side-effects were detected. The circulating silver levels confirm both the persistence of silver-coating activity after three years and the safety of silver-coated implants. Longer follow-up and larger series are needed.
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Affiliation(s)
- Guido Scoccianti
- Orthopaedic Oncology Unit, Careggi University-Hospital, Firenze, Italy.
| | - Filippo Frenos
- Orthopaedic Oncology Unit, Careggi University-Hospital, Firenze, Italy
| | - Giovanni Beltrami
- Orthopaedic Oncology Unit, Careggi University-Hospital, Firenze, Italy
| | | | - Rodolfo Capanna
- Orthopaedic Oncology Unit, Careggi University-Hospital, Firenze, Italy
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First Clinical Experience With Thermal-Sprayed Silver Oxide-Containing Hydroxyapatite Coating Implant. J Arthroplasty 2016; 31:1498-503. [PMID: 26810376 DOI: 10.1016/j.arth.2015.12.034] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 11/24/2015] [Accepted: 12/14/2015] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Prosthetic joint infection is a serious complication of implant therapy. To prevent prosthetic joint infection, we previously reported the features of silver oxide-containing hydroxyapatite (Ag-HA), which was prepared by mixing silver (a metal with antimicrobial activity) with HA. In this study, we evaluated the potential issues of total hip arthroplasty (THA) with an Ag-HA-coated implant. METHODS We prepared an implant for THA that was coated with Ag-HA. In this study, the implant contained silver at a maximum quantity of 2.9 mg/implant. In this prospective interventional study, we performed THA with this implant in 20 patients and investigated the effects of silver. RESULTS Blood silver levels peaked at 2 weeks after THA and gradually decreased thereafter. The highest blood silver level recorded during the postoperative follow-up was 6.0 ng/mL, which was within the normal range. The Harris Hip Scores increased in all cases, and activities of daily living improved markedly after THA with Ag-HA-coated implants. Implant failure was absent on radiography. No adverse reaction to silver was noted, and argyria was not observed in any case. No patients have developed infection after surgery. CONCLUSION This is the first clinical study of Ag-HA-coated implants in THA. Our Ag-HA-coated implants markedly improved patients' activities of daily living without causing any adverse reactions attributable to silver in the human body. Ag-HA is expected to reduce postoperative infections and prevent decreased quality of life in patients undergoing prosthetic arthroplasty, thus leading to more favorable outcomes.
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Eltorai AEM, Haglin J, Perera S, Brea BA, Ruttiman R, Garcia DR, Born CT, Daniels AH. Antimicrobial technology in orthopedic and spinal implants. World J Orthop 2016; 7:361-9. [PMID: 27335811 PMCID: PMC4911519 DOI: 10.5312/wjo.v7.i6.361] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/06/2016] [Accepted: 04/21/2016] [Indexed: 02/06/2023] Open
Abstract
Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions.
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The use of nanomaterials to treat bone infections. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 67:822-833. [PMID: 27287180 DOI: 10.1016/j.msec.2016.04.062] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 03/29/2016] [Accepted: 04/18/2016] [Indexed: 12/15/2022]
Abstract
A new era of osteomyelitis treatment has been taking strides towards efficient, local administration of antibiotics at the site of infection. By having them localized to the site of infection, this toxicity is no longer an issue and actually has shown to be a more productive treatment for osteomyelitis. Researchers have focused the production of non-biodegradable, antibiotic, infused bone cements specifically designed for proficient osteocyte binding, useful antibiotic release over a desirable period of time, and promotion of bone regeneration. These cements are then surgically placed on the infected site following debridement and irrigation. The problem, however, is that the use of ineffective cements and the overuse of antibiotics has led to the development of resistant bacteria. Due to this, further research is being done in the field of antibiotic discovery and delivery. Specifically, the development of biodegradable materials capable of efficiently delivering antibiotics and also eliminating the need for follow-up surgery to remove the delivery material is being done, thus reducing exposure risk. Nanoparticles have been developed in the forms of scaffolds and injections to deliver a higher degree and longer lasting duration of antibiotic release, while promoting bone regeneration.
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Ferraris S, Spriano S. Antibacterial titanium surfaces for medical implants. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 61:965-78. [DOI: 10.1016/j.msec.2015.12.062] [Citation(s) in RCA: 257] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 11/16/2015] [Accepted: 12/28/2015] [Indexed: 12/30/2022]
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Iodine-Supported Hip Implants: Short Term Clinical Results. BIOMED RESEARCH INTERNATIONAL 2015; 2015:368124. [PMID: 26583103 PMCID: PMC4637032 DOI: 10.1155/2015/368124] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 07/04/2015] [Accepted: 07/05/2015] [Indexed: 12/21/2022]
Abstract
We developed a new povidone iodine coating technology for titanium hip implants and performed a clinical trial to assess its usefulness in suppressing postoperative infection. Results indicate that iodine-supported titanium has favorable antibacterial activity, biocompatibility, and no cytotoxicity. Thirty joints in 28 patients were treated using iodine-supported implants. Fourteen joints were revision total hip arthroplasty (THA) after periprosthetic infection, 13 were primary THA for immunosuppressive conditions or pyogenic arthritis, and 3 were conversions from hemiarthroplasty to THA for immunosuppressive conditions. Two examinations were conducted sequentially until final follow-up: white blood cell (WBC) and C-reactive protein (CRP) were measured pre- and postoperatively and thyroid hormone levels in the blood were examined. The mean follow-up period was 33 months (14-78). There were no signs of infection in any patient at the last follow-up. WBC and CRP levels returned to normal within several weeks. No abnormalities of thyroid gland function were detected. Loosening of the implants did not occur in any patient. Excellent bone ingrowth and ongrowth were found around prostheses. No cytotoxicity or adverse effects were detected. These results suggest that iodine-supported THA implants can be highly effective in preventing and treating postoperative infections.
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Romanò CL, Scarponi S, Gallazzi E, Romanò D, Drago L. Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama. J Orthop Surg Res 2015; 10:157. [PMID: 26429342 PMCID: PMC4591707 DOI: 10.1186/s13018-015-0294-5] [Citation(s) in RCA: 187] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 09/16/2015] [Indexed: 02/07/2023] Open
Abstract
Implanted biomaterials play a key role in current success of orthopedic and trauma surgery. However, implant-related infections remain among the leading reasons for failure with high economical and social associated costs. According to the current knowledge, probably the most critical pathogenic event in the development of implant-related infection is biofilm formation, which starts immediately after bacterial adhesion on an implant and effectively protects the microorganisms from the immune system and systemic antibiotics. A rationale, modern prevention of biomaterial-associated infections should then specifically focus on inhibition of both bacterial adhesion and biofilm formation. Nonetheless, currently available prophylactic measures, although partially effective in reducing surgical site infections, are not based on the pathogenesis of biofilm-related infections and unacceptable high rates of septic complications, especially in high-risk patients and procedures, are still reported.In the last decade, several studies have investigated the ability of implant surface modifications to minimize bacterial adhesion, inhibit biofilm formation, and provide effective bacterial killing to protect implanted biomaterials, even if there still is a great discrepancy between proposed and clinically implemented strategies and a lack of a common language to evaluate them.To move a step forward towards a more systematic approach in this promising but complicated field, here we provide a detailed overview and an original classification of the various technologies under study or already in the market. We may distinguish the following: 1. Passive surface finishing/modification (PSM): passive coatings that do not release bactericidal agents to the surrounding tissues, but are aimed at preventing or reducing bacterial adhesion through surface chemistry and/or structure modifications; 2. Active surface finishing/modification (ASM): active coatings that feature pharmacologically active pre-incorporated bactericidal agents; and 3. Local carriers or coatings (LCC): local antibacterial carriers or coatings, biodegradable or not, applied at the time of the surgical procedure, immediately prior or at the same time of the implant and around it. Classifying different technologies may be useful in order to better compare different solutions, to improve the design of validation tests and, hopefully, to improve and speed up the regulatory process in this rapidly evolving field.
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Affiliation(s)
- Carlo Luca Romanò
- Department of Reconstructive Surgery of Osteo-articular Infections C.R.I.O. Unit, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
| | - Sara Scarponi
- Department of Reconstructive Surgery of Osteo-articular Infections C.R.I.O. Unit, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
| | - Enrico Gallazzi
- Department of Reconstructive Surgery of Osteo-articular Infections C.R.I.O. Unit, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
| | - Delia Romanò
- Department of Reconstructive Surgery of Osteo-articular Infections C.R.I.O. Unit, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
| | - Lorenzo Drago
- Laboratory of Clinical Chemistry and Microbiology, I.R.C.C.S. Galeazzi Orthopaedic Institute, Milan, Italy.
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Eto S, Miyamoto H, Shobuike T, Noda I, Akiyama T, Tsukamoto M, Ueno M, Someya S, Kawano S, Sonohata M, Mawatari M. Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur. J Orthop Res 2015; 33:1391-7. [PMID: 25808232 DOI: 10.1002/jor.22903] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 03/10/2015] [Indexed: 02/04/2023]
Abstract
Antibacterial silver with hydroxyapatite (Ag-HA) is a promising coating material for imparting antibacterial properties to implants. We previously reported that 3% (w/w) silver with HA (3% Ag-HA) has both antibacterial activity and osteoconductivity. In this study, we investigated the effects of Ag-HA on the in vitro osteoblast function and the in vivo anchorage strength and osteoconductivity of implants. Production of the osteoblast marker alkaline phosphatase, but not cytotoxicity, was observed in cells of the osteoblast cell line MC3T3-E1 cultured on the 3% Ag-HA-coated surface. These results were similar to those observed with silver-free HA coating. In contrast, a significant high level of cytotoxicity was observed when the cells were cultured on a 50% Ag-HA-coated surface. The anchorage strength of implants inserted into the femur of Sprague-Dawley (SD) rats was enhanced by coating the implants with 3% Ag-HA. On the 3% Ag-HA-coated surface, both metaphyseal and diaphyseal areas were largely covered with new bone and had adequate osteoconductivity. These results suggest that 3% Ag-HA, like conventional HA, promotes osteogenesis by supporting osteoblast viability and function and thereby contributes to sufficient anchorage strength of implants. Application of 3% Ag-HA, which combines the osteoconductivity of HA and the antibacterial activity of silver, to prosthetic joints will help prevent postoperative infections.
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Affiliation(s)
- Shuichi Eto
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Hiroshi Miyamoto
- Departments of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Takeo Shobuike
- Departments of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Iwao Noda
- Research Department, KYOCERA Medical Corporation, Osaka, 532-0003, Japan
| | - Takayuki Akiyama
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Masatsugu Tsukamoto
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Masaya Ueno
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Shinsuke Someya
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Shunsuke Kawano
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Motoki Sonohata
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Masaaki Mawatari
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
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Antibacterial surface treatment for orthopaedic implants. Int J Mol Sci 2014; 15:13849-80. [PMID: 25116685 PMCID: PMC4159828 DOI: 10.3390/ijms150813849] [Citation(s) in RCA: 179] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Revised: 06/06/2014] [Accepted: 06/13/2014] [Indexed: 02/07/2023] Open
Abstract
It is expected that the projected increased usage of implantable devices in medicine will result in a natural rise in the number of infections related to these cases. Some patients are unable to autonomously prevent formation of biofilm on implant surfaces. Suppression of the local peri-implant immune response is an important contributory factor. Substantial avascular scar tissue encountered during revision joint replacement surgery places these cases at an especially high risk of periprosthetic joint infection. A critical pathogenic event in the process of biofilm formation is bacterial adhesion. Prevention of biomaterial-associated infections should be concurrently focused on at least two targets: inhibition of biofilm formation and minimizing local immune response suppression. Current knowledge of antimicrobial surface treatments suitable for prevention of prosthetic joint infection is reviewed. Several surface treatment modalities have been proposed. Minimizing bacterial adhesion, biofilm formation inhibition, and bactericidal approaches are discussed. The ultimate anti-infective surface should be “smart” and responsive to even the lowest bacterial load. While research in this field is promising, there appears to be a great discrepancy between proposed and clinically implemented strategies, and there is urgent need for translational science focusing on this topic.
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Zaborowska M, Welch K, Brånemark R, Khalilpour P, Engqvist H, Thomsen P, Trobos M. Bacteria-material surface interactions: methodological development for the assessment of implant surface induced antibacterial effects. J Biomed Mater Res B Appl Biomater 2014; 103:179-87. [PMID: 24816674 DOI: 10.1002/jbm.b.33179] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Revised: 03/19/2014] [Accepted: 04/12/2014] [Indexed: 01/09/2023]
Abstract
The choice of material for implanted prostheses is of great importance concerning bacterial colonization and biofilm formation. Consequently, methods to investigate bacterial behavior are needed in order to develop new infection resistant surfaces. In this study, different methodological setups were used to evaluate the antimicrobial effect of photocatalytic titanium oxide and silver surfaces. Biofilm formation and eradication under static and dynamic culture conditions were studied with the use of the following analytical techniques: viable colony-forming unit (CFU) counting, imprinting, fluorescence, and bioluminescence. The present study demonstrates that different methods are needed in order to evaluate the prophylactic and treatment effects on planktonic and biofilm bacteria and to assess the antimicrobial effect of different surface treatments/coatings. Choosing the right antibacterial testing model for the specific application is also of great importance. Both in situ approaches and indirect methods provide valuable complementary information.
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Affiliation(s)
- Magdalena Zaborowska
- Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden
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Acute and subacute toxicity in vivo of thermal-sprayed silver containing hydroxyapatite coating in rat tibia. BIOMED RESEARCH INTERNATIONAL 2014; 2014:902343. [PMID: 24779019 PMCID: PMC3977419 DOI: 10.1155/2014/902343] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 02/13/2014] [Indexed: 11/17/2022]
Abstract
To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2-4 days after treatment) and subacute phase (4-12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.
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Braem A, Van Mellaert L, Mattheys T, Hofmans D, De Waelheyns E, Geris L, Anné J, Schrooten J, Vleugels J. Staphylococcal biofilm growth on smooth and porous titanium coatings for biomedical applications. J Biomed Mater Res A 2013; 102:215-24. [PMID: 23661274 DOI: 10.1002/jbm.a.34688] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 01/28/2013] [Accepted: 02/12/2013] [Indexed: 12/14/2022]
Abstract
Implant-related infections are a serious complication in prosthetic surgery, substantially jeopardizing implant fixation. As porous coatings for improved osseointegration typically present an increased surface roughness, their resulting large surface area (sometimes increasing with over 700% compared to an ideal plane) renders the implant extremely susceptible to bacterial colonization and subsequent biofilm formation. Therefore, there is particular interest in orthopaedic implantology to engineer surfaces that combine both the ability to improve osseointegration and at the same time reduce the infection risk. As part of this orthopaedic coating development, the interest of in vitro studies on the interaction between implant surfaces and bacteria/biofilms is growing. In this study, the in vitro staphylococcal adhesion and biofilm formation on newly developed porous pure Ti coatings with 50% porosity and pore sizes up to 50 μm is compared to various dense and porous Ti or Ti-6Al-4V reference surfaces. Multiple linear regression analysis indicates that surface roughness and hydrophobicity are the main determinants for bacterial adherence. Accordingly, the novel coatings display a significant reduction of up to five times less bacterial surface colonization when compared to a commercial state-of-the-art vacuum plasma sprayed coating. However, the results also show that a further expansion of the porosity with over 15% and/or the pore size up to 150 μm is correlated to a significant increase in the roughness parameters resulting in an ascent of bacterial attachment. Chemically modifying the Ti surface in order to improve its hydrophilicity, while preserving the average roughness, is found to strongly decrease bacteria quantities, indicating the importance of surface functionalization to reduce the infection risk of porous coatings.
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Affiliation(s)
- Annabel Braem
- Department of Metallurgy and Materials Engineering (MTM), KU Leuven, B-3001, Heverlee, Belgium
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Kluin OS, van der Mei HC, Busscher HJ, Neut D. Biodegradable vs non-biodegradable antibiotic delivery devices in the treatment of osteomyelitis. Expert Opin Drug Deliv 2013; 10:341-51. [PMID: 23289645 DOI: 10.1517/17425247.2013.751371] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
INTRODUCTION Chronic osteomyelitis, or bone infection, is a major worldwide cause of morbidity and mortality, as it is exceptionally hard to treat due to patient and pathogen-associated factors. Successful treatment requires surgical debridement together with long-term, high antibiotic concentrations that are best achieved by local delivery devices, either made of degradable or non-degradable materials. AREAS COVERED Non-degradable delivery devices are frequently constituted by polymethylmethacrylate-based carriers. Drawbacks are the need to remove the carrier (as the carrier itself may provide a substratum for bacterial colonization), inefficient release kinetics and incompatibility with certain antibiotics. These drawbacks have led to the quest for degradable alternatives, but also devices made of biodegradable calcium sulphate, collagen sponges, calcium phosphate or polylactic acids have their specific disadvantages. EXPERT OPINION Antibiotic treatment of osteomyelitis with the current degradable and non-degradable delivery devices is effective in the majority of cases. Degradable carriers have an advantage over non-degradable carriers that they do not require surgical removal. Synthetic poly(trimethylene carbonate) may be preferred in the future over currently approved lactic/glycolic acids, because it does not yield acidic degradation products. Moreover, degradable poly(trimethylene carbonate) yields a zero-order release kinetics that may not stimulate development of antibiotic-resistant bacterial strains due to the absence of long-term, low-concentration tail-release.
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Affiliation(s)
- Otto S Kluin
- Department of Biomedical Engineering, W. J. Kolff Institute, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen , The Netherlands
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