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Semeshchenko D, Slullitel PA, Farinati A, Albani-Forneris AF, Piuzzi NS, Buttaro MA. Unconventional Therapies in Periprosthetic Joint Infections: Prevention and Treatment: A Narrative Review. J Clin Med 2025; 14:2610. [PMID: 40283439 PMCID: PMC12027822 DOI: 10.3390/jcm14082610] [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: 01/27/2025] [Revised: 04/03/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND as the demand for total joint arthroplasty continues to grow each year, the healthcare burden is expected to increase due to periprosthetic joint infection (PJI). This review article aims to highlight the significance of biofilms in the pathogenesis of PJI and introduce alternative therapies that prevent bacterial adhesion to implants or enhance their eradication when infection occurs. SEARCH STRATEGY we conducted a bibliographic search in PubMed using the following MeSH terms as follows: "no antibiotic treatment of PJI", "bacterial biofilm eradication agents", and "unconventional prevention of PJI", among others. Most important results: after an initial analysis of the literature, we selected the most significant topics on novel PJI treatment methods and prevention strategies. A second PubMed search highlighted the following therapeutic modalities: the application of hydrogels on implant surfaces, the use of phage therapy, lysostaphin and antimicrobial peptides, the implementation of two-stage debridement, irrigation, implant retention and antibiotic therapy (DAIR), the intra-articular antibiotic infusion, and the use of methylene blue for biofilm eradication. CONCLUSIONS the use of new cement spacers with xylitol, ammonium compounds, or silver nanoparticles is another promising technique to increase the eradication rate in two-stage revision. It is important for professionals to deeply understand the pathogenesis of PJI and the role of biofilms in its development in order to become familiar with these novel techniques that could reduce the burdens on healthcare systems.
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Affiliation(s)
- Daniyil Semeshchenko
- ‘Sir John Charnley’ Hip Surgery Unit, Institute of Orthopaedics ‘Carlos E. Ottolenghi’, Italian Hospital of Buenos Aires, 4190 Perón St., Buenos Aires C1199ABH, Argentina
- Institute of Medical and Health Sciences Research (IIMCS), Faculty of Medicine, Salvador University, 1601 Córdoba Av., Buenos Aires C1055AAG, Argentina
| | - Pablo A. Slullitel
- ‘Sir John Charnley’ Hip Surgery Unit, Institute of Orthopaedics ‘Carlos E. Ottolenghi’, Italian Hospital of Buenos Aires, 4190 Perón St., Buenos Aires C1199ABH, Argentina
| | - Alicia Farinati
- Institute of Medical and Health Sciences Research (IIMCS), Faculty of Medicine, Salvador University, 1601 Córdoba Av., Buenos Aires C1055AAG, Argentina
| | - Agustin F. Albani-Forneris
- ‘Sir John Charnley’ Hip Surgery Unit, Institute of Orthopaedics ‘Carlos E. Ottolenghi’, Italian Hospital of Buenos Aires, 4190 Perón St., Buenos Aires C1199ABH, Argentina
| | - Nicolas S. Piuzzi
- Department of Orthopaedic Surgery Cleveland, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
| | - Martin A. Buttaro
- ‘Sir John Charnley’ Hip Surgery Unit, Institute of Orthopaedics ‘Carlos E. Ottolenghi’, Italian Hospital of Buenos Aires, 4190 Perón St., Buenos Aires C1199ABH, Argentina
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Burduja N, Virzì NF, Nocito G, Ginestra G, Saita MG, Spitaleri F, Patanè S, Nostro A, Pittalà V, Mazzaglia A. Curcumin-laden hydrogel coating medical device for periprosthetic joint infection prevention and control. Int J Pharm 2025; 672:125283. [PMID: 39890088 DOI: 10.1016/j.ijpharm.2025.125283] [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: 12/09/2024] [Revised: 01/24/2025] [Accepted: 01/25/2025] [Indexed: 02/03/2025]
Abstract
The Periprosthetic Joint Infection (PJI) is one of the most important complications of the joint arthroplasty. This surgical procedure is rising worldwide and is further affecting the public health because of the widespread resistance to antibiotics. New therapeutic strategies and innovative antimicrobial biomaterials development are needed to eradicate pathogens without inducing resistance and accelerating recovery. In this direction, herein Curcumin I- (Cur-) loaded DAC® (Defensive Antibacterial Coating, a hydrogel based on hyaluronic acid conjugated to polylactic acid, hereafter named DAC) has been built on. To incorporate Cur in the DAC, thus obtaining Cur-DAC (Cur ≅ 0.93 mg/g), the generally recognized as safe (GRAS) propylene glycol (PG) was used as cosolvent. The drugs combinations of Cur (≅ 0.93 mg/g) and Vancomycin (Van) (at low dose that is ≅ 0.033 mg/g) within the hydrogel (Cur/Van-DAC) was alsoexperienced . Hydrogels were prepared and characterized by rheological investigations and their erosion together with the drug release profile over the time evaluated in physiological conditions. The nanohydrogels produced upon water dilution were characterized by AFM, DLS, and UV/Vis absorption and emission spectroscopies. Superior Cur stability over pH-, solvent- and photoinduced degradations resulted in the DAC matrix. The photoinduced antimicrobial activity of Cur-DAC against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium was evaluated by spreading loaded DAC-based hydrogel onto titanium disk mimicking prosthesis, thus detecting a good reduction of bacterial load after 30 min of exposure to light and a subsequent decrease of cells number at 24 h in the absence of nutrients. The drug association in Cur/Van-DAC demonstrated the best activity against MRSA, even in the presence of nutrients, with respect to established DAC loaded with high amounts of Van (ranging from 18.7 mg/g to 45.8 mg/g) used during the surgery, due to the photoantibacterial activity of Cur, becoming promising to prevent and control joint infections.
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Affiliation(s)
- Nina Burduja
- National Research Council, Institute of Nanostructured Materials (CNR-ISMN) URT of Messina at Dept. of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy
| | - Nicola F Virzì
- Department of Drug and Health Science, University of Catania, Viale Andrea Doria 6 95125 Catania, Italy
| | - Giuseppe Nocito
- National Research Council, Institute of Nanostructured Materials (CNR-ISMN) URT of Messina at Dept. of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy
| | - Giovanna Ginestra
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy
| | - Maria G Saita
- Medivis, Via Carnazza 34/C 95030 Tremestieri Etneo, Italy
| | | | - Salvatore Patanè
- Department of Mathematical and Computer Sciences, Physical Sciences and Earth Sciences (MIFT), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy
| | - Antonia Nostro
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy
| | - Valeria Pittalà
- Department of Drug and Health Science, University of Catania, Viale Andrea Doria 6 95125 Catania, Italy.
| | - Antonino Mazzaglia
- National Research Council, Institute of Nanostructured Materials (CNR-ISMN) URT of Messina at Dept. of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale Ferdinando Stagno d'Alcontres, 31 98166 Messina, Italy.
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Mostafazade R, Tazik Z, Emami SA, Nesměrák K, Štícha M, Soheili V, Akaberi M. Isolation and Characterization of Fungal Endophytes From Helichrysum oocephalum, Evaluating Their Antimicrobial Activities, and Annotation of Their Metabolites. Chem Biodivers 2025:e202402236. [PMID: 40007502 DOI: 10.1002/cbdv.202402236] [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: 09/08/2024] [Revised: 01/31/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025]
Abstract
Antibiotic resistance is one of the biggest threats to global health. Fungal endophytes are important sources of active natural products with antimicrobial potential. The purpose of this study was to characterize the endophytes coexisting with Helichrysum oocephalum, evaluate their antimicrobial activities, and annotate the endophytes metabolites. Six fungal species, including Fusarium avenaceum and Fusarium tricinctum, were identified. Endophytes were cultured, and their metabolites were extracted. The antimicrobial effects of the extracts were tested against Staphylococcus aureus, Bacillus cereus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. In addition, anti-biofilm effects of the extracts were examined against P. aeruginosa and S. epidermidis. The metabolites in the most active extract were annotated on the basis of the LC-ESI-QToF-MS/MS data. In anti-biofilm studies, F. avenaceum extract was effective in destroying and inhibiting the biofilm formation of S. epidermidis. LC-MS analysis showed that most of the identified compounds in the active extracts were enniatins (cyclic hexadepsipeptides). However, apicidin derivatives were also annotated. Our results revealed that these endophytes, especially Fusarium species, have antimicrobial activity against S. aureus, B. cereus, and C. albicans and anti-biofilm activity against S. epidermidis. According to the literature, the observed antimicrobial activity can be attributed to the enniatins. However, further phytochemical and pharmacological studies are necessary in this regard.
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Affiliation(s)
- Reza Mostafazade
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Tazik
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Ahmad Emami
- Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Karel Nesměrák
- Department of Analytical Chemistry, Faculty of Science, Charles University, Prague, Czech Republic
| | - Martin Štícha
- Mass Spectrometry Laboratory, Section of Chemistry, Faculty of Science, Charles University, Prague, Czech Republic
| | - Vahid Soheili
- Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Akaberi
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Boyer B, Cazorla C, Carricajo A, Labruyere C, Chapelle C, Presles E, Zufferey P, Botelho-Nevers E. Single-stage surgery with antibiotic-loaded hydrogel-coated implants versus two-stage surgery for chronic periprosthetic hip joint infection in French tertiary referral hospitals: the SINBIOSE-H non-inferiority, randomised, controlled trial study protocol. BMJ Open 2025; 15:e085146. [PMID: 40000087 DOI: 10.1136/bmjopen-2024-085146] [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] [Indexed: 02/27/2025] Open
Abstract
INTRODUCTION Chronic hip prosthetic joint infection (PJI) treatment needs non-conservative surgery. The recommended treatment follows a two-stage protocol. Between the two surgeries, full-weight bearing is prohibited, and joint stiffness and pain are rather usual complications. The single-stage procedure is thought to be less susceptible to late functional complications with a shorter, single hospital stay. However, infection control could be less efficient; the protocol highly relies on antibiotics and has a list of contra-indications. Most of these contra-indications are directly related to the biofilm formation. As no randomised control trial has ever compared single-stage versus two-stage surgery on infection treatment, the level of evidence for recommending one procedure over the other is low. An antibiotic-loaded hydrogel coating (Defensive Antiadhesive Coating (DAC), Novagenit SRL) has been proven to mechanically prevent biofilm formation while allowing a prolonged intra-articular antibiotic release. The addition of this biofilm inhibitor to a single-stage surgery might stand as a promising strategy for PJI. Moreover, using this device to prevent biofilm formation could expand one-stage surgery to patients who are in theory contra-indicated to one-stage surgery. METHODS AND ANALYSIS SINBIOSE-H is a Prospective Randomized Open, Blinded End-point clinical trial that will include patients with a chronic hip PJI as defined by the Musculoskeletal Infection Society (MSIS), with at least one theoretical contra-indication for single-stage surgery. Patients needing a cemented implant will not be included. 440 patients will be randomised in two groups: the experimental group is composed of single-stage procedure associated with the use of biofilm inhibitor (DAC) loaded with topical antibiotics, and the control group is composed of two-stage procedure without biofilm inhibitor. The primary objective will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is non-inferior to two-stage surgery for chronic hip PJI treatment. The secondary objectives will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is superior to two-stage surgery on the prevention of functional complications, patient satisfaction scores, death rate, postoperative complications or early revision surgery for any cause other than infection. Based on a failure rate of two-stage surgery of 20% and a reduction of the infection rate using the DAC biofilm inhibitor from 3 to 0.7%, with a non-inferiority margin of 1.35 and power set at 90%, we estimated to enrol 420 patients. ETHICS AND DISSEMINATION The protocol is in accordance with ethical principles established by the Helsinki World Medical Assembly and its amendments and will be conducted in accordance with the recommendations of International Conference on Harmonisation Good Clinical Practice. A core information and informed consent form will be provided. The written approval of the Ethics Committee (EC)/Institutional Review Board (IRB) together with the approved subject information/informed consent forms must be filed in the study files. Written informed consent must be obtained before any study-specific procedure takes place. The data will be saved on the internal network in a secured directory, dedicated to the study. At the end of the research, all documents (case report files, investigator files, etc) will be archived and stored for 15 years in each centre. Data on SAEs will be included in the study documentation file. All data and documents will be made available if requested by relevant authorities. The EC and IRB were submitted and approved in France (CPP Ile De France X, 93 602 AULNAY-SOUS-BOIS). Ethics approval covers all centres. TRIAL REGISTRATION NUMBER The study is registered on clinicaltrials.org under NCT04251377 (EUDRACT NUMBER, 2019-A01491-56; trial sponsor, St Etienne University Hospital Center; date of the last version, 24 February 2006).
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Affiliation(s)
- Bertrand Boyer
- SAnté INgéniérie BIOlogie St-Etienne, Saint-Priest-en-Jarez, France
- Department of Orthopedics, St Etienne University Hospital Center, Saint-Priest-en-Jarez, France
| | - Celine Cazorla
- Department of Infectious Diseases, CIC-1408, Saint-Priest-en-Jarez, France
- Department of Infectious Diseases and Hygiene, St Etienne University Hospital Center, Saint-Priest-en-Jarez, France
| | - Anne Carricajo
- Department of Microbiology, CIC1408, Saint-Priest-en-Jarez, France
- Department of Microbiology, Centre International de Recherche en Infectiologie, Lyon, France
| | - Carine Labruyere
- Unité de Recherche Clinique Innovation et Pharmacologie, Saint-Priest-en-Jarez, France
| | - Céline Chapelle
- Université Jean Monnet, Saint-Étienne, France
- Unité de Recherche Clinique Innovation et Pharmacologie, Saint-Etienne, France
| | - Emilie Presles
- Inserm CIC1408, Saint-Etienne University Hospital Centre, Saint-Etienne, France
| | - Paul Zufferey
- University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France
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Corona PS, Vicens MH, Fraile R, Amat C, Vicente M. Distal femur replacement for infected bone defects due to end-stage periprosthetic joint infection or trauma: a staged strategy protocol using the stemless Compress® device protected with a fast resorbable antibiotic-loaded hydrogel. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY & TRAUMATOLOGY : ORTHOPEDIE TRAUMATOLOGIE 2025; 35:72. [PMID: 39948170 DOI: 10.1007/s00590-025-04177-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/15/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND Distal femur replacement (DFR) with a stemmed megaprosthesis represents a challenge due to high rates of loosening and limited reconstructive options if the implant fails. Such an unfavourable scenario is even more complex where there are also infected bone defects. The Compress® device was developed to provide an alternative to traditional intramedullary stems. We report on the outcomes of a staged protocol using the Compress® DFR, protected with a vancomycin-gentamicin-loaded hydrogel, in infected non-oncological scenarios. METHODS Retrospective longitudinal cohort study including patients with infected defects of the distal femur following orthopaedic trauma or periprosthetic joint infection (PJI) and managed with the protocol described. Protocol features, microbiological data, radiological results, complications, infection control, and implant survivorship were assessed. Minimum follow-up was 18 months or until implant removal. RESULTS 21 cases of Compress® DFR were included. On average, patients had 4.9 prior surgeries and 14.5 cm distal femur bone defects after pseudo-oncological resection. After median follow-up of 42 months (18-83 months), no infection recurrence occurred; limb salvage was achieved in all cases. Five patients experienced aseptic loosening, all within the first 7 post-operative months. Beyond this time threshold, no further implant failures were observed, resulting in a cumulative implant survival rate of 75% at 1 and 5 years, and of 75% at final follow-up. CONCLUSION Staged Compress® DFR with antibiotic-loaded hydrogel protection is a reliable option for selected patients with distal femoral bone defects, offering high infection control, durable implant survivorship, and simplified revision. Aseptic failures occurred primarily within the early post-operative months, highlighting the need for close monitoring during this critical period. This approach provides a promising solution for complex non-oncological cases involving infected distal femoral bone defects.
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Affiliation(s)
| | | | - Rosa Fraile
- Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Carles Amat
- Vall d'Hebron Hospital Universitari, Barcelona, Spain
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Bove A, Braile A, Matino G, Del Regno N, Sirico S, Orabona N, Braile M. The Efficacy of Defensive Antibacterial Coating (DAC™) Periprosthetic Joint Infection Prevention in the Hip: A Systematic Review. J Clin Med 2025; 14:270. [PMID: 39797352 PMCID: PMC11722025 DOI: 10.3390/jcm14010270] [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: 12/05/2024] [Revised: 12/27/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025] Open
Abstract
Background: Periprosthetic joint infections (PJIs) are a significant issue in joint replacement surgery patients, affecting results and mortality. Recent research focuses on developing hydrogels (HG) and antimicrobial coatings to reduce pressure injuries, with DAC™ HG showing lower infection risk in hip revision surgery. However, the effectiveness of DAC™ hydrogel in PIJs is still unknown. Here, we attempt to update the literature in this field, pointing out methodological flaws and providing guidance for further research. Methods: We conducted a systematic literature review using the PRISMA guidelines. Quality assessment was performed with the Newcastle-Ottawa Scale (NOS) and the Coleman Methodology Score (CMS). Results: Among 27 records from the initial search, 3 studies resulted eligible for final evaluation. It was observed that following the three surgical procedures performed in combination with DAC™ loaded with specific antibiotics, the quality of life of the treated patients had improved. No side effects associated with DAC™ treatment were in fact observed. Conclusions: The amount and quality of scientific evidence are yet insufficient to either encourage or dissuade the use of such hydrogels in hip prosthesis, despite some intriguing first results. These challenges will be better addressed by randomized controlled trials or longitudinal prospective investigations.
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Affiliation(s)
- Antonio Bove
- Unit of Orthopaedics and Traumatology, Ospedale del Mare, 80147 Naples, Italy; (A.B.); (A.B.); (G.M.); (N.D.R.); (N.O.)
| | - Adriano Braile
- Unit of Orthopaedics and Traumatology, Ospedale del Mare, 80147 Naples, Italy; (A.B.); (A.B.); (G.M.); (N.D.R.); (N.O.)
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy
- Department of Clinical Sciences and Translational Medicine, University of Tor Vergata, 00133 Rome, Italy
| | - Giovanni Matino
- Unit of Orthopaedics and Traumatology, Ospedale del Mare, 80147 Naples, Italy; (A.B.); (A.B.); (G.M.); (N.D.R.); (N.O.)
| | - Nicola Del Regno
- Unit of Orthopaedics and Traumatology, Ospedale del Mare, 80147 Naples, Italy; (A.B.); (A.B.); (G.M.); (N.D.R.); (N.O.)
| | | | - Nicola Orabona
- Unit of Orthopaedics and Traumatology, Ospedale del Mare, 80147 Naples, Italy; (A.B.); (A.B.); (G.M.); (N.D.R.); (N.O.)
| | - Mariantonia Braile
- Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy
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Gehrke T, Citak M, Parvizi J, Budhiparama NC, Akkaya M. Periprosthetic joint infections: state-of-the-art. Arch Orthop Trauma Surg 2024; 145:58. [PMID: 39694911 DOI: 10.1007/s00402-024-05627-5] [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: 06/04/2024] [Accepted: 11/14/2024] [Indexed: 12/20/2024]
Abstract
In general, periprosthetic joint infection (PJI) is regarded as one of the most common complications of total joint arthroplasty (TJA) and may lead to surgical failure, revision surgery, amputation or death. Nowadays, PJI has become a global health concern, which brings a great burden to public healthcare. In addition, there are still obstacles to achieve high success rates in the prevention, diagnosis and treatment of PJI. However, promising studies are also available with the advancements in biotechnology. This article will present an overview of the current methods used in the prevention, diagnosis and management of PJI while underlining the new technologies utilized.
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Affiliation(s)
- Thorsten Gehrke
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Hamburg, Germany
| | - Mustafa Citak
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Hamburg, Germany
| | - Javad Parvizi
- Department of International Joint Center, Acibadem, Istanbul, Maslak, Turkey
| | | | - Mustafa Akkaya
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Hamburg, Germany.
- Department of Orthopaedics and Traumatology, Yuksek Ihtisas University, Faculty of Medicine, Ankara, Turkey.
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Baidya A, Budiman A, Jain S, Oz Y, Annabi N. Engineering Tough and Elastic Polyvinyl Alcohol-Based Hydrogel with Antimicrobial Properties. ADVANCED NANOBIOMED RESEARCH 2024; 4:2300173. [PMID: 39650171 PMCID: PMC11620288 DOI: 10.1002/anbr.202300173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2024] Open
Abstract
Hydrogels have been extensively used for tissue engineering applications due to their versatility in structure and physical properties, which can mimic native tissues. Although significant progress has been made towards designing hydrogels for soft tissue repair, engineering hydrogels that resemble load-bearing tissues is still considered a great challenge due to their specific mechano-physical demands. Here, we report microporous, tough, yet highly compressible poly(vinyl alcohol) (PVA)-based hydrogels for potential applications in repairing or replacing different load-bearing tissues. The synergy of freeze-thawing and the Hofmeister effect, which controlled the spatial arrangement and aggregation of polymer chains, facilitated the formation of micro-structured frameworks with tunable porosity. While the maximum mechanical strength, toughness, and stretchability of the engineered hydrogel were ~390 kPa, ~388 kJ/m3, and ~170%, respectively, the Young's modulus based on compression testing was found to be in the range of ~0.02 - 0.30 MPa, highlighting the all-in-one mechanically enriched nature of the hydrogel system. Furthermore, the minimal swelling and degradation rate of the engineered hydrogel met the specific requirements of load-bearing tissues. Finally, excellent antibacterial resistance as well as in vitro biocompatibility of the hydrogel demonstrated its potential for the replacement of load-bearing tissues.
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Affiliation(s)
- Avijit Baidya
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Annabella Budiman
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Saumya Jain
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Yavuz Oz
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Nasim Annabi
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095, United States
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Seregina T, Shelomentsev I, Krivoborodov E, Vaniushenkova A, Toropygin I, Dyatlov A, Lukashov N, Dyatlov V. Physicochemical and Biological Properties of Vancomycin-Containing Antibacterial Polysaccharide Gels for Biocomposite Bone Implant Impregnation. Biomacromolecules 2024; 25:4156-4167. [PMID: 38922325 DOI: 10.1021/acs.biomac.4c00268] [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: 06/27/2024]
Abstract
Polymeric drugs containing up to 60% by weight of the antibiotic vancomycin were synthesized based on dextran carriers activated with epichlorohydrin. Vancomycin was covalently bound, involving the primary amino group of the molecule through the hydroxypropyl radical to the C6 position of the anhydroglucose units of the dextran main chain. Covalent binding is necessary to prevent spontaneous release of the antibiotic from the gel, thereby reducing the risk of bacterial multiresistance. Antibacterial depot gels were obtained from those polymers, containing up to 17.5% by weight of polysaccharide with a cross-linking density of q = 3-5 nodes per macromolecule for the deposition of another type of drugs not covalently bound to the polymer gel. They were used to coat the surface of the internal pores of biocomposite bone implants based on bovine cancellous bone used in orthopedics. The chemical structure of the polymer was studied using 13C NMR spectroscopy and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The stiffness of the gels was evaluated by the values of the accumulation modulus G' = 170-270 kPa and the loss modulus G″ = 3.7-4.2 kPa determined on a rheometer. Their values are close to those typical for materials used to replace soft tissue in plastic surgery. The minimum inhibitory concentration of the gels against Staphylococcus aureus P209 depends on the antibiotic content in the polymer. It equals 2.5 mg/L for vancomycin we used and 100 mg/L for a polymer containing 50% by weight of covalently bound antibiotic. The cytotoxic concentration measured with cell culture HEK 293T exceeds 1200 mg/L in 24 h exposure. The release dynamics of drugs not covalently bound to dextran from the depot gel were studied using fluorescein as a model. The release time is independent of the gel density and lasts up to 6 days for a 2 mm thick layer. Both the gel and the bone implants impregnated with it maintained consistently high antibacterial activity throughout the experiment, up to its completion after 168 h, with the local concentration of the released antibiotic at the site of bacterial attack exceeding the therapeutic level by 200 times.
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Affiliation(s)
- Tatiana Seregina
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Ilya Shelomentsev
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Efrem Krivoborodov
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Anna Vaniushenkova
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Ilya Toropygin
- V. N. Orekhovich Institute of Biomedical Chemistry, Pogodinskaya str., 10, p. 8, 119121 Moscow, Russia
| | - Alexander Dyatlov
- The Hebrew University of Jerusalem, POB 12272, Jerusalem 9112000, Israel
| | - Nikolay Lukashov
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Valerie Dyatlov
- D. I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
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Corona PS, Vargas Meouchi EA, García Hernández JM, Soriano RF, Crespo-Fresno A, Issa-Benítez D, Mudaris MA, Soldado F. Single-stage transcutaneous osseointegrated prosthesis for above-knee amputations including an antibiotic-loaded hydrogel. Preliminary results of a new surgical protocol. Injury 2024; 55:111424. [PMID: 38402710 DOI: 10.1016/j.injury.2024.111424] [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: 08/28/2023] [Revised: 12/08/2023] [Accepted: 02/10/2024] [Indexed: 02/27/2024]
Abstract
INTRODUCTION Patients with above-knee amputations (AKA) are normally treated with the traditional socket-mounted prosthesis (SMP), which is associated with a high incidence of problems. Osseointegration has been proposed as a promising option for avoiding many common SMP drawbacks. Several concerns have arisen regarding amputee osseointegration, however, mainly with respect to infection. We report on the safety of a single-stage osseointegration protocol using an antibiotic-loaded hydrogel to coat the intramedullary implant. MATERIALS AND METHODS We retrospectively reviewed all AKA cases treated at our center between January 2019 and April 2022, in which a transcutaneous osseointegrated implant was used in a single-stage strategy, together with a rapid-resorbable hydrogel loaded with vancomycin and gentamicin. The specific protocol used, infection rate, implant osseointegration rate and implant survivorship were determined after a minimum follow-up of 12 months. RESULTS Eleven osseointegration cases were included in the study, with an average of 16 years post-amputation (range: 3-35 years). After a median follow-up of 24 months (range 12-49 months) no patient had suffered any implant-related infection. Osseointegration of the implant had been achieved in all cases. The mid-term survivorship of the implant in our series was 100 % at the end of follow-up. Radiographs of all cases showed no loosening of the implant. Further, 91 % of the series patients were able to walk without restrictions after the rehabilitation process. CONCLUSIONS The single-stage osseointegration protocol for AKA, using a rapid-resorbable hydrogel loaded with vancomycin and gentamicin, yields low rates of implant-related deep infection. This protocol consistently delivers high rates of radiological osseointegration, with no hydrogel-associated complications.
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Affiliation(s)
- Pablo S Corona
- Septic and Reconstructive Surgery Unit (UCSO), Orthopaedic Surgery Department, Vall d'Hebrón University Hospital, Barcelona, Spain; Orthopaedic Surgery Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Musculoskeletal Tissue Engineering Group, Vall d'Hebrón Research Institute (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Spain
| | - Enrique A Vargas Meouchi
- Orthopaedic Surgery Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Musculoskeletal Tissue Engineering Group, Vall d'Hebrón Research Institute (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Spain.
| | | | - Rosa Fraile Soriano
- Septic and Reconstructive Surgery Unit (UCSO), Orthopaedic Surgery Department, Vall d'Hebrón University Hospital, Barcelona, Spain; Surgical nurse team, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Almudena Crespo-Fresno
- Amputee Unit, Physical Medicine and Rehabilitation Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Daniela Issa-Benítez
- Amputee Unit, Physical Medicine and Rehabilitation Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Munjed Al Mudaris
- Department of Orthopaedic Surgery, Macquarie University Hospital, Macquarie University, Sydney, Australia
| | - Francisco Soldado
- Pediatric Orthopedic Surgery Department, Vall d'Hebron University Hospital, Barcelona, Spain Universitat Autònoma de Barcelona, Spain; Pediatric Hand Surgery and Microsurgery Unit. Barcelona University Children´s Hospital HM Nens, Barcelona, Spain
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11
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Lei Z, Liang H, Sun W, Chen Y, Huang Z, Yu B. A biodegradable PVA coating constructed on the surface of the implant for preventing bacterial colonization and biofilm formation. J Orthop Surg Res 2024; 19:175. [PMID: 38459593 PMCID: PMC10921624 DOI: 10.1186/s13018-024-04662-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/02/2024] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND Bone implant infections pose a critical challenge in orthopedic surgery, often leading to implant failure. The potential of implant coatings to deter infections by hindering biofilm formation is promising. However, a shortage of cost-effective, efficient, and clinically suitable coatings persists. Polyvinyl alcohol (PVA), a prevalent biomaterial, possesses inherent hydrophilicity, offering potential antibacterial properties. METHODS This study investigates the PVA solution's capacity to shield implants from bacterial adhesion, suppress bacterial proliferation, and thwart biofilm development. PVA solutions at concentrations of 5%, 10%, 15%, and 20% were prepared. In vitro assessments evaluated PVA's ability to impede bacterial growth and biofilm formation. The interaction between PVA and mCherry-labeled Escherichia coli (E. coli) was scrutinized, along with PVA's therapeutic effects in a rat osteomyelitis model. RESULTS The PVA solution effectively restrained bacterial proliferation and biofilm formation on titanium implants. PVA solution had no substantial impact on the activity or osteogenic potential of MC3T3-E1 cells. Post-operatively, the PVA solution markedly reduced the number of Staphylococcus aureus and E. coli colonies surrounding the implant. Imaging and histological scores exhibited significant improvements 2 weeks post-operation. Additionally, no abnormalities were detected in the internal organs of PVA-treated rats. CONCLUSIONS PVA solution emerges as an economical, uncomplicated, and effective coating material for inhibiting bacterial replication and biofilm formation on implant surfaces, even in high-contamination surgical environments.
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Affiliation(s)
- Zhonghua Lei
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
- Department of Orthopedics, The Sixth Peoples Hospital of Huizhou, Huizhou, 516211, China
| | - Haifeng Liang
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
- Department of Orthopedics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
| | - Wei Sun
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Yan Chen
- Ultrasound Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Zhi Huang
- Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410083, China.
| | - Bo Yu
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
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12
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Nakahara I, Ando W, Enami H, Kamihata S, Takashima K, Uemura K, Hamada H, Sugano N. Therapeutic efficacy of vancomycin-loaded carbon fiber-reinforced polyetheretherketone hip stem for periprosthetic joint infection: A pilot study. J Orthop Res 2024; 42:474-483. [PMID: 37728980 DOI: 10.1002/jor.25691] [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: 05/30/2023] [Revised: 08/15/2023] [Accepted: 09/14/2023] [Indexed: 09/22/2023]
Abstract
A carbon fiber-reinforced polyetheretherketone (CFR/PEEK) hip stem with a special antibiotic elution mechanism is under development to treat periprosthetic joint infection (PJI). The antibiotic elution characteristics of intramedullary implants were experimentally investigated, and the efficacy of revision surgery using a therapeutic stem in treating ovine PJI was examined. To evaluate elution characteristics, the intramedullary vancomycin-loaded CFR/PEEK cylindrical implants were inserted in the distal femur of nine sheep, and the vancomycin elution rate was measured at 2, 7, and 21 days. To evaluate therapeutic efficacy, the PJI model with staphylococcus aureus was attempted to create for five sheep. Moreover, the therapeutic vancomycin-loaded CFR/PEEK stem was implanted during one-stage revision surgery. Three weeks after revision surgery, the treatment efficacy was evaluated based on bacterial cultures and wound findings. In addition, the vancomycin elution rate from the stem was measured. On average, the cylindrical implants eluted approximately 70% vancomycin in 21 days. Of the five sheep attempting to create a PJI model, three were successfully infected with S. aureus as intended for verification of treatment efficacy. In all three joints, negative bacterial cultures and no purulence were observed 3 weeks after revision surgery. The vancomycin elution rates from the stems were >70%. Efficient elution of vancomycin was confirmed by the experimental implant inserted into the bone marrow and the stem in actual PJI treatment. Using a novel therapeutic stem with an antibiotic elution mechanism in one-stage revision surgery, successful treatment was demonstrated in all S. aureus-induced PJIs.
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Affiliation(s)
- Ichiro Nakahara
- Department of Orthopaedic Surgery, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan
| | - Wataru Ando
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hideaki Enami
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Satoshi Kamihata
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuma Takashima
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Keisuke Uemura
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hidetoshi Hamada
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Nobuhiko Sugano
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
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13
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Rahnama-Hezavah M, Mertowska P, Mertowski S, Skiba J, Krawiec K, Łobacz M, Grywalska E. How Can Imbalance in Oral Microbiota and Immune Response Lead to Dental Implant Problems? Int J Mol Sci 2023; 24:17620. [PMID: 38139449 PMCID: PMC10743591 DOI: 10.3390/ijms242417620] [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: 11/16/2023] [Revised: 12/09/2023] [Accepted: 12/14/2023] [Indexed: 12/24/2023] Open
Abstract
Dental implantology is one of the most dynamically developing fields of dentistry, which, despite developing clinical knowledge and new technologies, is still associated with many complications that may lead to the loss of the implant or the development of the disease, including peri-implantitis. One of the reasons for this condition may be the fact that dental implants cannot yield a proper osseointegration process due to the development of oral microbiota dysbiosis and the accompanying inflammation caused by immunological imbalance. This study aims to present current knowledge as to the impact of oral microflora dysbiosis and deregulation of the immune system on the course of failures observed in dental implantology. Evidence points to a strong correlation between these biological disturbances and implant complications, often stemming from improper osseointegration, pathogenic biofilms on implants, as well as an exacerbated inflammatory response. Technological enhancements in implant design may mitigate pathogen colonization and inflammation, underscoring implant success rates.
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Affiliation(s)
- Mansur Rahnama-Hezavah
- Chair and Department of Oral Surgery, Medical University of Lublin, 20-093 Lublin, Poland; (M.R.-H.); (M.Ł.)
| | - Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (S.M.); (E.G.)
| | - Sebastian Mertowski
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (S.M.); (E.G.)
| | - Julia Skiba
- Student Research Group of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Karol Krawiec
- Student Research Group of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Michał Łobacz
- Chair and Department of Oral Surgery, Medical University of Lublin, 20-093 Lublin, Poland; (M.R.-H.); (M.Ł.)
| | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (S.M.); (E.G.)
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14
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De Meo D, Martini P, Pennarola MF, Guarascio G, Rivano Capparuccia M, Iaiani G, Candela V, Gumina S, Villani C. Hydrogel Coating versus Calcium Sulphate Beads as a Local Antibiotic Carrier for Debridement Procedures in Acute Periprosthetic Joint Infection: A Preliminary Study. Gels 2023; 9:758. [PMID: 37754439 PMCID: PMC10530128 DOI: 10.3390/gels9090758] [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: 07/23/2023] [Revised: 09/11/2023] [Accepted: 09/11/2023] [Indexed: 09/28/2023] Open
Abstract
Periprosthetic joint infections (PJI) are among the most difficult complications to treat in orthopaedic surgery. Debridement, antibiotics, and implant retention (DAIR) represent an efficient strategy for acute PJI, especially when resorbable local antibiotic carriers and coatings are used. The aim of this pilot study was to evaluate the difference between using antibiotic-loaded hydrogel (ALH) and calcium sulphate (CS) beads in the DAIR procedure. We analysed 16 patients who had been treated since 2018 for acute PJI, namely eight patients with knee PJI (50%), seven with hip PJI (43.7%), and one with shoulder PJI (6.2%). Nine patients were treated with the Debridement, Antibiotic Coating and Retention of the Implant (DACRI) method, while seven were treated with the Debridement, Antibiotic Pearls, Retention of the Implant (DAPRI) method. We found no significant differences between the two groups in terms of age, sex, the American Society of Anesthesiologists risk score, Charlson Comorbidity Index, localisation, days from onset to diagnosis and pathogenesis. Furthermore, no differences were found between the DACRI and DAPRI groups in terms of infection control (15 patients, 93.75% with p = 0.36) and last C-Reactive Protein values (p = 0.26), with a mean follow-up of 26.1 ± 7.7 months. Treatment for one patient affected by knee Candida albicans PJI in the DACRI group was not successful. In conclusion, DAPRI and DACRI appear to be safe and effective treatments for PJIs. This evidence will encourage the development of new clinical research into local carriers and coatings for use in acute implant-associated infections.
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Affiliation(s)
- Daniele De Meo
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
| | - Paolo Martini
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
| | - Maria Francesca Pennarola
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
| | - Giovanni Guarascio
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
| | - Marco Rivano Capparuccia
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00100 Rome, Italy
| | - Giancarlo Iaiani
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00100 Rome, Italy
| | - Vittorio Candela
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
| | - Stefano Gumina
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
| | - Ciro Villani
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, 00100 Rome, Italy; (P.M.); (M.F.P.); (G.G.); (V.C.); (S.G.); (C.V.)
- M.I.T.O. (Malattie Infettive in Traumatologia e Ortopedia-Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (M.R.C.); (G.I.)
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15
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Visan AI, Cristescu R. Polysaccharide-Based Coatings as Drug Delivery Systems. Pharmaceutics 2023; 15:2227. [PMID: 37765196 PMCID: PMC10537422 DOI: 10.3390/pharmaceutics15092227] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/21/2023] [Accepted: 08/27/2023] [Indexed: 09/29/2023] Open
Abstract
Therapeutic polysaccharide-based coatings have recently emerged as versatile strategies to transform a conventional medical implant into a drug delivery system. However, the translation of these polysaccharide-based coatings into the clinic as drug delivery systems still requires a deeper understanding of their drug degradation/release profiles. This claim is supported by little or no data. In this review paper, a comprehensive description of the benefits and challenges generated by the polysaccharide-based coatings is provided. Moreover, the latest advances made towards the application of the most important representative coatings based on polysaccharide types for drug delivery are debated. Furthermore, suggestions/recommendations for future research to speed up the transition of polysaccharide-based drug delivery systems from the laboratory testing to clinical applications are given.
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Affiliation(s)
- Anita Ioana Visan
- National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Street, 077125 Magurele, Ilfov, Romania
| | - Rodica Cristescu
- National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Street, 077125 Magurele, Ilfov, Romania
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16
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Pressato D, Battista A, Govoni M, Vivarelli L, Dallari D, Pellegrini A. The Intraoperative Use of Defensive Antibacterial Coating (DAC ®) in the Form of a Gel to Prevent Peri-Implant Infections in Orthopaedic Surgery: A Clinical Narrative Review. MATERIALS (BASEL, SWITZERLAND) 2023; 16:5304. [PMID: 37570009 PMCID: PMC10420205 DOI: 10.3390/ma16155304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/21/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023]
Abstract
Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient's quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology.
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Affiliation(s)
- Daniele Pressato
- Clinical and Scientific Affairs, Novagenit S.r.l., 38017 Mezzolombardo, Italy
| | - Angela Battista
- Quality Assurance and Regulatory Affairs, Novagenit S.r.l., 38017 Mezzolombardo, Italy;
| | - Marco Govoni
- Reconstructive Orthopaedic Surgery and Innovative Techniques—Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (L.V.); (D.D.)
| | - Leonardo Vivarelli
- Reconstructive Orthopaedic Surgery and Innovative Techniques—Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (L.V.); (D.D.)
| | - Dante Dallari
- Reconstructive Orthopaedic Surgery and Innovative Techniques—Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (L.V.); (D.D.)
| | - Antonio Pellegrini
- Reconstructive Surgery and Septic Complications Surgery Center, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy;
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17
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De Meo D, Cera G, Pica R, Perfetti F, Martini P, Perciballi B, Ceccarelli G, Persiani P, Villani C. Antibiotic-Loaded Coatings to Reduce Fracture-Related Infections: Retrospective Case Series of Patients with Increased Infectious Risk. Antibiotics (Basel) 2023; 12:287. [PMID: 36830197 PMCID: PMC9952500 DOI: 10.3390/antibiotics12020287] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
Local antibiotic delivery strategies have been increasingly employed for the prevention of fracture-related infections (FRIs). The aim of this study is to evaluate the efficacy and safety of antibiotic-coated implants in the prevention of FRIs after surgical treatment in patients with increased infectious risk. A retrospective observational study has been conducted on patients with upper and lower limb fractures treated with internal fixation or prosthetic replacements, using a gentamicin coated nail (CN) and/or antibiotic-loaded hydrogel applied to the implant of choice (ALH). The study included 37 patients (20 M, 17 F), with a mean age of 63 years. The mean estimated preoperative infectious risk score was 6.4%. ALH was used in 27 cases, tibial CNs were implanted in 4 cases, and both were employed in 6 cases. The antibiotics used locally were gentamicin in 72.97% of cases (27 patients) and a combination of gentamicin + vancomycin in 27.03% of cases (10 patients). Mean follow-up was 32 months. Only one case (2.94%) showed onset of FRI at 5 months after surgery. Local antibiotic prophylaxis by coating resulted in a reduction in the incidence FRI, as compared to the estimated preoperative risk. The use of ALH allows for the choice of antibiotic; however, the application of antibiotics seems more nonuniform when applied to a nail.
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Affiliation(s)
- Daniele De Meo
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Gianluca Cera
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
| | - Roberta Pica
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
| | - Fabiano Perfetti
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
| | - Paolo Martini
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Beatrice Perciballi
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Giancarlo Ceccarelli
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy
- Department of Public Health and Infectious Diseases—Sapienza, University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy
| | - Pietro Persiani
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
| | - Ciro Villani
- Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro, 3, 00185 Rome, Italy
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy
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18
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He C, Yue Y, Li R, Huang Y, Shu L, Lv H, Wang J, Zhang Z. Sodium hyaluronates applied in the face affects the diversity of skin microbiota in healthy people. Int J Cosmet Sci 2023. [PMID: 36710533 DOI: 10.1111/ics.12845] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/15/2022] [Accepted: 01/27/2023] [Indexed: 01/31/2023]
Abstract
OBJECTIVE A healthy and stable microbiome has many beneficial effects on the host, while an unbalanced or disordered microbiome can lead to various skin diseases. Hyaluronic acid is widely used in the cosmetics and pharmaceutical industries; however, specific reports on its effect on the skin microflora of healthy people have not been published. This study aimed to determine the effect of sodium hyaluronate on the facial microflora of healthy individuals. METHODS Face of 20 healthy female volunteers between 18 and 24 years was smeared with sodium hyaluronate solution once per day. Cotton swabs were used to retrieve samples on days 0, 14, and 28, and high-throughput sequencing of 16 S rRNA was used to determine the changes in bacterial community composition. RESULTS Facial application of HA can reduce the abundance of pathogenic bacteria, such as Cutibacterium and S. aureus, and increase the colonization of beneficial bacteria. CONCLUSION This is the first intuitive report to demonstrate the effect of hyaluronic acid on facial microflora in healthy people. Accordingly, sodium hyaluronate was found to have a positive effect on facial skin health.
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Affiliation(s)
- Chen He
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - YingXue Yue
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruilong Li
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yiping Huang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Luan Shu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Huixia Lv
- Special Cosmetics R&D Joint laboratory of China Pharmaceutical University & Bloomage Biotechnology Corporation Limited, Nanjing, China
| | - Jing Wang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenhai Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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19
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Kapusta O, Jarosz A, Stadnik K, Giannakoudakis DA, Barczyński B, Barczak M. Antimicrobial Natural Hydrogels in Biomedicine: Properties, Applications, and Challenges-A Concise Review. Int J Mol Sci 2023; 24:2191. [PMID: 36768513 PMCID: PMC9917233 DOI: 10.3390/ijms24032191] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/18/2023] [Accepted: 01/19/2023] [Indexed: 01/24/2023] Open
Abstract
Natural hydrogels are widely used as biomedical materials in many areas, including drug delivery, tissue scaffolds, and particularly wound dressings, where they can act as an antimicrobial factor lowering the risk of microbial infections, which are serious health problems, especially with respect to wound healing. In this review article, a number of promising strategies in the development of hydrogels with biocidal properties, particularly those originating from natural polymers, are briefly summarized and concisely discussed. Common strategies to design and fabricate hydrogels with intrinsic or stimuli-triggered antibacterial activity are exemplified, and the mechanisms lying behind these properties are also discussed. Finally, practical antibacterial applications are also considered while discussing the current challenges and perspectives.
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Affiliation(s)
- Oliwia Kapusta
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, 20031 Lublin, Poland
| | - Anna Jarosz
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, 20031 Lublin, Poland
| | - Katarzyna Stadnik
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, 20031 Lublin, Poland
| | | | - Bartłomiej Barczyński
- 1st Department of Oncological Gynecology and Gynecology, Medical University in Lublin, 20-059 Lublin, Poland
| | - Mariusz Barczak
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, 20031 Lublin, Poland
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20
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The Potential of Surface-Immobilized Antimicrobial Peptides for the Enhancement of Orthopaedic Medical Devices: A Review. Antibiotics (Basel) 2023; 12:antibiotics12020211. [PMID: 36830122 PMCID: PMC9952162 DOI: 10.3390/antibiotics12020211] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023] Open
Abstract
Due to the well-known phenomenon of antibiotic resistance, there is a constant need for antibiotics with novel mechanisms and different targets respect to those currently in use. In this regard, the antimicrobial peptides (AMPs) seem very promising by virtue of their bactericidal action, based on membrane permeabilization of susceptible microbes. Thanks to this feature, AMPs have a broad activity spectrum, including antibiotic-resistant strains, and microbial biofilms. Additionally, several AMPs display properties that can help tissue regeneration. A possible interesting field of application for AMPs is the development of antimicrobial coatings for implantable medical devices (e.g., orthopaedic prostheses) to prevent device-related infection. In this review, we will take note of the state of the art of AMP-based coatings for orthopaedic prostheses. We will review the most recent studies by focusing on covalently linked AMPs to titanium, their antimicrobial efficacy and plausible mode of action, and cytocompatibility. We will try to extrapolate some general rules for structure-activity (orientation, density) relationships, in order to identify the most suitable physical and chemical features of peptide candidates, and to optimize the coupling strategies to obtain antimicrobial surfaces with improved biological performance.
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21
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Kennedy DG, O’Mahony AM, Culligan EP, O’Driscoll CM, Ryan KB. Strategies to Mitigate and Treat Orthopaedic Device-Associated Infections. Antibiotics (Basel) 2022; 11:1822. [PMID: 36551479 PMCID: PMC9774155 DOI: 10.3390/antibiotics11121822] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/03/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022] Open
Abstract
Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for patients and healthcare providers. This review delineates the pathogenesis of orthopaedic implant infections and the challenges that arise due to biofilm formation and the implications for treatment. It focuses on research advancements in the development of next-generation orthopaedic medical devices to mitigate against implant-related infections. Key considerations impacting the development of devices, which must often perform multiple biological and mechanical roles, are delineated. We review technologies designed to exert spatial and temporal control over antimicrobial presentation and the use of antimicrobial surfaces with intrinsic antibacterial activity. A range of measures to control bio-interfacial interactions including approaches that modify implant surface chemistry or topography to reduce the capacity of bacteria to colonise the surface, form biofilms and cause infections at the device interface and surrounding tissues are also reviewed.
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Affiliation(s)
- Darragh G. Kennedy
- School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland
- Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
| | | | - Eamonn P. Culligan
- Department of Biological Sciences, Munster Technological University, T12 P928 Cork, Ireland
| | | | - Katie B. Ryan
- School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland
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22
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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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23
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Li J, Cheung WH, Chow SK, Ip M, Leung SYS, Wong RMY. Current therapeutic interventions combating biofilm-related infections in orthopaedics : a systematic review of in vivo animal studies. Bone Joint Res 2022; 11:700-714. [PMID: 36214177 PMCID: PMC9582863 DOI: 10.1302/2046-3758.1110.bjr-2021-0495.r3] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Aims Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714.
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Affiliation(s)
- Jie Li
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Wing-Hoi Cheung
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Simon K. Chow
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Margaret Ip
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Sharon Y. S. Leung
- School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China
| | - Ronald M. Y. Wong
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China, Ronald Man Yeung Wong. E-mail:
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24
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LOGROSCINO G, SARACCO M. Hip periprosthetic joint infections: prevention, diagnosis and treatment. MINERVA ORTHOPEDICS 2022; 73. [DOI: 10.23736/s2784-8469.21.04186-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2023]
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25
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Visperas A, Santana D, Klika AK, Higuera‐Rueda CA, Piuzzi NS. Current treatments for biofilm-associated periprosthetic joint infection and new potential strategies. J Orthop Res 2022; 40:1477-1491. [PMID: 35437846 PMCID: PMC9322555 DOI: 10.1002/jor.25345] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 04/11/2022] [Accepted: 04/16/2022] [Indexed: 02/04/2023]
Abstract
Periprosthetic joint infection (PJI) remains a devastating complication after total joint arthroplasty. Bacteria involved in these infections are notorious for adhering to foreign implanted surfaces and generating a biofilm matrix. These biofilms protect the bacteria from antibiotic treatment and the immune system making eradication difficult. Current treatment strategies including debridement, antibiotics, and implant retention, and one- and two-stage revisions still present a relatively high overall failure rate. One of the main shortcomings that has been associated with this high failure rate is the lack of a robust approach to treating bacterial biofilm. Therefore, in this review, we will highlight new strategies that have the potential to combat PJI by targeting biofilm integrity, therefore giving antibiotics and the immune system access to the internal network of the biofilm structure. This combination antibiofilm/antibiotic therapy may be a new strategy for PJI treatment while promoting implant retention.
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Affiliation(s)
- Anabelle Visperas
- Department of Orthopaedic SurgeryCleveland Clinic FoundationClevelandOhioUSA
| | - Daniel Santana
- Department of Orthopaedic SurgeryCleveland Clinic FoundationClevelandOhioUSA
- Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOhioUSA
| | - Alison K. Klika
- Department of Orthopaedic SurgeryCleveland Clinic FoundationClevelandOhioUSA
| | | | - Nicolas S. Piuzzi
- Department of Orthopaedic SurgeryCleveland Clinic FoundationClevelandOhioUSA
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26
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Bohara S, Suthakorn J. Surface coating of orthopedic implant to enhance the osseointegration and reduction of bacterial colonization: a review. Biomater Res 2022; 26:26. [PMID: 35725501 PMCID: PMC9208209 DOI: 10.1186/s40824-022-00269-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 05/11/2022] [Indexed: 12/11/2022] Open
Abstract
The use of orthopedic implants in surgical technology has fostered restoration of physiological functions. Along with successful treatment, orthopedic implants suffer from various complications and fail to offer functions correspondent to native physiology. The major problems include aseptic and septic loosening due to bone nonunion and implant site infection due to bacterial colonization. Crucial advances in material selection in the design and development of coating matrixes an opportunity for the prevention of implant failure. However, many coating materials are limited in in-vitro testing and few of them thrive in clinical tests. The rate of implant failure has surged with the increasing rates of revision surgery creating physical and sensitive discomfort as well as economic burdens. To overcome critical pathogenic activities several systematic coating techniques have been developed offering excellent results that combat infection and enhance bone integration. This review article includes some more common implant coating matrixes with excellent in vitro and in vivo results focusing on infection rates, causes, complications, coating materials, host immune responses and significant research gaps. This study provides a comprehensive overview of potential coating technology, with functional combination coatings which are focused on ultimate clinical practice with substantial improvement on in-vivo tests. This includes the development of rapidly growing hydrogel coating techniques with the potential to generate several accurate and precise coating procedures.
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Affiliation(s)
- Smriti Bohara
- Department of Biomedical Engineering, Center for Biomedical and Robotics Technology (BART LAB), Faculty of Engineering, Mahidol University, Salaya, Thailand
| | - Jackrit Suthakorn
- Department of Biomedical Engineering, Center for Biomedical and Robotics Technology (BART LAB), Faculty of Engineering, Mahidol University, Salaya, Thailand
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27
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WPI Hydrogels with a Prolonged Drug-Release Profile for Antimicrobial Therapy. Pharmaceutics 2022; 14:pharmaceutics14061199. [PMID: 35745772 PMCID: PMC9231275 DOI: 10.3390/pharmaceutics14061199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/28/2022] [Accepted: 06/02/2022] [Indexed: 12/10/2022] Open
Abstract
Infectious sequelae caused by surgery are a significant problem in modern medicine due to their reduction of therapeutic effectiveness and the patients’ quality of life.Recently, new methods of local antimicrobial prophylaxis of postoperative sequelae have been actively developed. They allow high local concentrations of drugs to be achieved, increasing the antibiotic therapy’s effectiveness while reducing its side effects. We have developed and characterized antimicrobial hydrogels based on an inexpensive and biocompatible natural substance from the dairy industry—whey protein isolate—as matrices for drug delivery. The release of cefazolin from the pores of hydrogel structures directly depends on the amount of the loaded drug and occurs in a prolonged manner for three days. Simultaneously with the antibiotic release, hydrogel swelling and partial degradation occurs. The WPI hydrogels absorb solvent, doubling in size in three days and retaining cefazolin throughout the duration of the experiment. The antimicrobial activity of cefazolin-loaded WPI hydrogels against Staphylococcus aureus growth is prolonged in comparison to that of the free cefazolin. The overall cytotoxic effect of cefazolin-containing WPI hydrogels is lower than that of free antibiotics. Thus, our work shows that antimicrobial WPI hydrogels are suitable candidates for local antibiotic therapy of infectious surgical sequelae.
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28
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Snetkov P, Rogacheva E, Kremleva A, Morozkina S, Uspenskaya M, Kraeva L. In-Vitro Antibacterial Activity of Curcumin-Loaded Nanofibers Based on Hyaluronic Acid against Multidrug-Resistant ESKAPE Pathogens. Pharmaceutics 2022; 14:pharmaceutics14061186. [PMID: 35745759 PMCID: PMC9227118 DOI: 10.3390/pharmaceutics14061186] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/29/2022] [Accepted: 05/30/2022] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections have accompanied humanity throughout its history and became vitally important in the pandemic area. The most pathogenic bacteria are multidrug-resistant strains, which have become widespread due to their natural biological response to the use of antibiotics, including uncontrolled use. The current challenge is finding highly effective antibacterial agents of natural origin, which, however, have low solubility and consequently poor bioavailability. Curcumin, derived from Curcuma longa, is an example of a natural biologically active agent with a wide spectrum of biological effects, particularly against Gram-positive bacteria. However, curcumin exhibits extremely low antibacterial activity against Gram-negative bacteria. Curcumin’s hydrophobicity limits its use in medicine. As such, various polymeric systems have been used, especially biopolymer-based electrospun nanofibers. In the present study, the technological features of the fabrication of curcumin-loaded hyaluronic acid-based nanofibers are discussed in detail, their morphological characteristics, wettability, physico-chemical properties, and curcumin release profiles are demonstrated, and their antibacterial activity against multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are evaluated. It is noteworthy that the fibers containing a stable HA–curcumin complex showed high antibacterial activity against both Gram-positive and Gram-negative bacteria, which is an undeniable advantage. It is expected that the results of this work will contribute to the development of antibacterial drugs for topical and internal use with high efficacy and considerably lower side effects.
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Affiliation(s)
- Petr Snetkov
- Center of Chemical Engineering, ITMO University, Kronverkskiy Prospekt, 49, bldg. A, 197101 St. Petersburg, Russia; (S.M.); (M.U.)
- Correspondence:
| | - Elizaveta Rogacheva
- Saint-Petersburg Pasteur Institute, Street Mira, 14, 197101 St. Petersburg, Russia; (E.R.); (L.K.)
| | - Arina Kremleva
- Institute of Advanced Data Transfer Systems, ITMO University, Kronverkskiy Prospekt, 49, bldg. A, 197101 St. Petersburg, Russia;
| | - Svetlana Morozkina
- Center of Chemical Engineering, ITMO University, Kronverkskiy Prospekt, 49, bldg. A, 197101 St. Petersburg, Russia; (S.M.); (M.U.)
| | - Mayya Uspenskaya
- Center of Chemical Engineering, ITMO University, Kronverkskiy Prospekt, 49, bldg. A, 197101 St. Petersburg, Russia; (S.M.); (M.U.)
| | - Liudmila Kraeva
- Saint-Petersburg Pasteur Institute, Street Mira, 14, 197101 St. Petersburg, Russia; (E.R.); (L.K.)
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29
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Xin W, Gao Y, Yue B. Recent Advances in Multifunctional Hydrogels for the Treatment of Osteomyelitis. Front Bioeng Biotechnol 2022; 10:865250. [PMID: 35547176 PMCID: PMC9081433 DOI: 10.3389/fbioe.2022.865250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
Osteomyelitis (OM), a devastating disease caused by microbial infection of bones, remains a major challenge for orthopedic surgeons. Conventional approaches for prevention and treatment of OM are unsatisfactory. Various alternative strategies have been proposed, among which, hydrogel-based strategies have demonstrated potential due to their unique properties, including loadable, implantable, injectable, printable, degradable, and responsive to stimuli. Several protocols, including different hydrogel designs, selection of antimicrobial agent, co-administration of bone morphogenetic protein 2 (BMP 2), and nanoparticles, have been shown to improve the biological properties, including antimicrobial effects, osteo-induction, and controlled drug delivery. In this review, we describe the current and future directions for designing hydrogels and their applications to improve the biological response to OM in vivo.
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30
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Bargavi P, Chandran RR, Durgalakshmi D, Rajashree P, Ramya R, Balakumar S. Drug infused Al 2O 3-bioactive glass coatings toward the cure of orthopedic infection. Prog Biomater 2022; 11:79-94. [PMID: 35094302 DOI: 10.1007/s40204-022-00181-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 01/11/2022] [Indexed: 11/27/2022] Open
Abstract
A unique implant coated substrate with dual-drug-eluting system exhibiting antibacterial, anti-inflammatory, and bone regenerative capacity has been fabricated using spray pyrolysis deposition (SPD) method. Bioglass (BG) and BG-alumina (BG-Al) composites coatings with different concentrations of Al incorporated on BG network over the Cp-Ti substrate were fabricated using SPD technique. Phase purity of BG and BG-Al composites were analyzed by XRD in which Na2Ca2Si3O9 and β-Na2Ca4(PO4)2SiO4) and Na7.15(Al7.2Si8.8O32) phases were formed. Surface morphology of the coated substrates was analyzed by SEM. Uniformity of the coatings were evaluated by surface profilometer and the uniform distribution the nanoparticles were confirmed with Elemental mapping. Systematically, each apatite layer formation on coated substrate was confirmed by immersing the samples for 1, 3, and 7 days in simulated body fluid and the needle-like structure was characterized using SEM. Cumulative release of Tetracycline hydrochloride (Tet) antibiotic and Dexamethasone (Dex) anti-inflammatory drug-loaded BG-Al and BG-Al composite-coated substrate were studied for 24 h. Antibacterial activity of the coated substrates were evaluated by time-dependent growth inhibition and minimal inhibitory concentration (MIC) assays in which BG-Al and BG-Al composite loaded with Tet showed considerable growth inhibition against S. aureus. Osteoblast-like cells (MG-63) exhibited profound proliferation with no cytotoxic effects which was due to release of Dex drug-coated substrates. Thus, surface modification of Cp-Ti substrate with BG, BG-Al composites coatings loaded with Tet and Dex drug can be considered for post-operative orthopedic implant infection application.
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Affiliation(s)
- P Bargavi
- National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai, 600 025, India
| | - R Riju Chandran
- National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai, 600 025, India
| | - D Durgalakshmi
- Department of Medical Physics, Anna University, Chennai, 600 025, India
| | - P Rajashree
- CAS in Crystallography & Biophysics, University of Madras, Guindy campus, Chennai, 600 025, India
| | - R Ramya
- Saveetha Dental College & Hospitals, SIMTS, Poonamallee High Road, Chennai, 600089, India
| | - S Balakumar
- National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai, 600 025, India.
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31
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Carpa R, Remizovschi A, Culda CA, Butiuc-Keul AL. Inherent and Composite Hydrogels as Promising Materials to Limit Antimicrobial Resistance. Gels 2022; 8:70. [PMID: 35200452 PMCID: PMC8870943 DOI: 10.3390/gels8020070] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/22/2021] [Accepted: 01/11/2022] [Indexed: 01/25/2023] Open
Abstract
Antibiotic resistance has increased significantly in the recent years, and has become a global problem for human health and the environment. As a result, several technologies for the controlling of health-care associated infections have been developed over the years. Thus, the most recent findings in hydrogel fabrication, particularly antimicrobial hydrogels, could offer valuable solutions for these biomedical challenges. In this review, we discuss the most promising strategies in the development of antimicrobial hydrogels and the application of hydrogels in the treatment of microbial infections. The latest advances in the development of inherently and composite antimicrobial hydrogels will be discussed, as well as hydrogels as carriers of antimicrobials, with a focus on antibiotics, metal nanoparticles, antimicrobial peptides, and biological extracts. The emergence of CRISR-Cas9 technology for removing the antimicrobial resistance has led the necessity of new and performant carriers for delivery of the CRISPR-Cas9 system. Different delivery systems, such as composite hydrogels and many types of nanoparticles, attracted a great deal of attention and will be also discussed in this review.
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Affiliation(s)
- Rahela Carpa
- Molecular Biology and Biotechnology Department, Faculty of Biology and Geology, Babeş-Bolyai University, 1 M. Kogalniceanu Street, 400084 Cluj-Napoca, Romania; (R.C.); (A.L.B.-K.)
- Center of Systems Biology, Biodiversity and Bioresources, Babeş-Bolyai University, 5-7 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Alexei Remizovschi
- Molecular Biology and Biotechnology Department, Faculty of Biology and Geology, Babeş-Bolyai University, 1 M. Kogalniceanu Street, 400084 Cluj-Napoca, Romania; (R.C.); (A.L.B.-K.)
- Center of Systems Biology, Biodiversity and Bioresources, Babeş-Bolyai University, 5-7 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Carla Andreea Culda
- Parasitology and Parasitic Diseases Department, University of Agricultural Sciences and Veterinary Medicine, 3-5 Calea Manastur Street, 400372 Cluj-Napoca, Romania;
| | - Anca Livia Butiuc-Keul
- Molecular Biology and Biotechnology Department, Faculty of Biology and Geology, Babeş-Bolyai University, 1 M. Kogalniceanu Street, 400084 Cluj-Napoca, Romania; (R.C.); (A.L.B.-K.)
- Center of Systems Biology, Biodiversity and Bioresources, Babeş-Bolyai University, 5-7 Clinicilor Street, 400006 Cluj-Napoca, Romania
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Sánchez-Bodón J, Andrade del Olmo J, Alonso JM, Moreno-Benítez I, Vilas-Vilela JL, Pérez-Álvarez L. Bioactive Coatings on Titanium: A Review on Hydroxylation, Self-Assembled Monolayers (SAMs) and Surface Modification Strategies. Polymers (Basel) 2021; 14:165. [PMID: 35012187 PMCID: PMC8747097 DOI: 10.3390/polym14010165] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/15/2022] Open
Abstract
Titanium (Ti) and its alloys have been demonstrated over the last decades to play an important role as inert materials in the field of orthopedic and dental implants. Nevertheless, with the widespread use of Ti, implant-associated rejection issues have arisen. To overcome these problems, antibacterial properties, fast and adequate osseointegration and long-term stability are essential features. Indeed, surface modification is currently presented as a versatile strategy for developing Ti coatings with all these challenging requirements and achieve a successful performance of the implant. Numerous approaches have been investigated to obtain stable and well-organized Ti coatings that promote the tailoring of surface chemical functionalization regardless of the geometry and shape of the implant. However, among all the approaches available in the literature to functionalize the Ti surface, a promising strategy is the combination of surface pre-activation treatments typically followed by the development of intermediate anchoring layers (self-assembled monolayers, SAMs) that serve as the supporting linkage of a final active layer. Therefore, this paper aims to review the latest approaches in the biomedical area to obtain bioactive coatings onto Ti surfaces with a special focus on (i) the most employed methods for Ti surface hydroxylation, (ii) SAMs-mediated active coatings development, and (iii) the latest advances in active agent immobilization and polymeric coatings for controlled release on Ti surfaces.
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Affiliation(s)
- Julia Sánchez-Bodón
- Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain; (J.S.-B.); (J.A.d.O.); (I.M.-B.); (J.L.V.-V.)
| | - Jon Andrade del Olmo
- Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain; (J.S.-B.); (J.A.d.O.); (I.M.-B.); (J.L.V.-V.)
- i+Med S. Coop, Parque Tecnológico de Alava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spain;
| | - Jose María Alonso
- i+Med S. Coop, Parque Tecnológico de Alava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spain;
| | - Isabel Moreno-Benítez
- Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain; (J.S.-B.); (J.A.d.O.); (I.M.-B.); (J.L.V.-V.)
| | - José Luis Vilas-Vilela
- Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain; (J.S.-B.); (J.A.d.O.); (I.M.-B.); (J.L.V.-V.)
- BCMaterials, Basque Center for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain
| | - Leyre Pérez-Álvarez
- Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain; (J.S.-B.); (J.A.d.O.); (I.M.-B.); (J.L.V.-V.)
- BCMaterials, Basque Center for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain
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Pala E, Trovarelli G, Ippolito V, Berizzi A, Ruggieri P. A long-term experience with Mutars tumor megaprostheses: analysis of 187 cases. Eur J Trauma Emerg Surg 2021; 48:2483-2491. [PMID: 34727192 DOI: 10.1007/s00068-021-01809-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 10/07/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Modular megaprostheses have widely replaced allografts, as a reconstructive option; however, failures of these devices remain high. Aim of this study was to analyze outcomes, survival of the implants, incidence and types of complications with Mutars modular endoprostheses at long term. METHODS Between 2000 and 2019, 187 Mutars prostheses were implanted in two dedicated centers: 72 upper limbs and 115 lower limbs reconstructions. Diagnoses included 107 primary malignant bone or soft tissue tumors, 65 metastases, 8 benign bone tumors and 7 non-oncologic cases. Silver-coated prostheses were used in 118/187 (63%) cases. RESULTS At last follow-up, 76.5% of patients had retained their implant. The overall failure rate was 23.5% at a mean of 1.7 years. There were 22 mechanical failures and 22 non-mechanical failures. The overall implant survival to all types of failure was 68% and 52% at 5 and 10 years, respectively. Infection was the most common mode of failure with an incidence of 6.9%. Implant survival to infection was better for silver-coated implants than for standard implants even if with no significant difference (p = 0.56). Functional results were satisfactory in 97% of patients. CONCLUSIONS The overall implant survival at long term was satisfactory with Mutars prostheses. The incidence of complications with Mutars prosthesis is in line with the incidence reported in the literature with other types of tumor prosthesis. The most frequent cause of failure was infection with a lower incidence in silver-coated prostheses; silver coating seems to prevent infection in distal femur and proximal tibia. The silver coating seems to be particularly useful in two-stage revisions with a lower incidence of secondary amputation. In higher risk patients, silver-coated prostheses are the preferable choice for the reduction of the reinfection rate. The functional results of Mutars prostheses were excellent or good in most of cases. The current paper is design to enhance the literature on megaprosthesis in tumor surgery, proven that this system is one of the most used all over the word and one of the best performing.
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Affiliation(s)
- Elisa Pala
- Department of Orthopedics and Ortopedic Oncology, University of Padova, Via Giustiniani 3, 35128, Padua, Italy
| | - Giulia Trovarelli
- Department of Orthopedics and Ortopedic Oncology, University of Padova, Via Giustiniani 3, 35128, Padua, Italy
| | - Vincenzo Ippolito
- Department of Orthopedics and Ortopedic Oncology, University of Padova, Via Giustiniani 3, 35128, Padua, Italy
| | - Antonio Berizzi
- Department of Orthopedics and Ortopedic Oncology, University of Padova, Via Giustiniani 3, 35128, Padua, Italy
| | - Pietro Ruggieri
- Department of Orthopedics and Ortopedic Oncology, University of Padova, Via Giustiniani 3, 35128, Padua, Italy.
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Kasza K, Gurnani P, Hardie KR, Cámara M, Alexander C. Challenges and solutions in polymer drug delivery for bacterial biofilm treatment: A tissue-by-tissue account. Adv Drug Deliv Rev 2021; 178:113973. [PMID: 34530014 DOI: 10.1016/j.addr.2021.113973] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/12/2021] [Accepted: 09/08/2021] [Indexed: 02/07/2023]
Abstract
To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial communities (biofilms) are a particular concern in this context. Biofilms are responsible for most human infections and are inherently less susceptible to antibiotic treatments. Biofilms have been linked with several challenging chronic diseases, including implant-associated osteomyelitis and chronic wounds. The specific local environments present in the infected tissues further contribute to the rise in antibiotic resistance by limiting the efficacy of systemic antibiotic therapies and reducing drug concentrations at the infection site, which can lead to reoccurring infections. To overcome the shortcomings of systemic drug delivery, encapsulation within polymeric carriers has been shown to enhance antimicrobial efficacy, permeation and retention at the infection site. In this Review, we present an overview of current strategies for antimicrobial encapsulation within polymeric carriers, comparing challenges and solutions on a tissue-by-tissue basis. We compare challenges and proposed drug delivery solutions from the perspective of the local environments for biofilms found in oral, wound, gastric, urinary tract, bone, pulmonary, vaginal, ocular and middle/inner ear tissues. We will also discuss future challenges and barriers to clinical translation for these therapeutics. The following Review demonstrates there is a significant imbalance between the research focus being placed on different tissue types, with some targets (oral and wound biofims) being extensively more studied than others (vaginal and otitis media biofilms and endocarditis). Furthermore, the importance of the local tissue environment when selecting target therapies is demonstrated, with some materials being optimal choices for certain sites of bacterial infection, while having limited applicability in others.
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Esteban J, Vallet-Regí M, Aguilera-Correa JJ. Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections. Antibiotics (Basel) 2021; 10:1270. [PMID: 34680850 PMCID: PMC8532710 DOI: 10.3390/antibiotics10101270] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/05/2021] [Accepted: 10/13/2021] [Indexed: 01/04/2023] Open
Abstract
Prosthetic joint infection (PJI) is the second most common cause of arthroplasty failure. Though infrequent, it is one of the most devastating complications since it is associated with great personal cost for the patient and a high economic burden for health systems. Due to the high number of patients that will eventually receive a prosthesis, PJI incidence is increasing exponentially. As these infections are provoked by microorganisms, mainly bacteria, and as such can develop a biofilm, which is in turn resistant to both antibiotics and the immune system, prevention is the ideal approach. However, conventional preventative strategies seem to have reached their limit. Novel prevention strategies fall within two broad categories: (1) antibiotic- and (2) heavy metal-based surface modifications of titanium alloy prostheses. This review examines research on the most relevant titanium alloy surface modifications that use antibiotics to locally prevent primary PJI.
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Affiliation(s)
- Jaime Esteban
- Clinical Microbiology Department, Jiménez Díaz Foundation Health Research Institute, Autonomous University of Madrid, Av. Reyes Católicos 2, 28040 Madrid, Spain
- Networking Research Centre on Infectious Diseases (CIBER-ID), 28029 Madrid, Spain
| | - María Vallet-Regí
- Department of Chemistry in Pharmaceutical Sciences, Research Institute Hospital 12 de Octubre (i+12), School of Pharmacy, Complutense University of Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain
- Networking Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
| | - John J Aguilera-Correa
- Networking Research Centre on Infectious Diseases (CIBER-ID), 28029 Madrid, Spain
- Department of Chemistry in Pharmaceutical Sciences, Research Institute Hospital 12 de Octubre (i+12), School of Pharmacy, Complutense University of Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain
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De Meo D, Ceccarelli G, Iaiani G, Lo Torto F, Ribuffo D, Persiani P, Villani C. Clinical Application of Antibacterial Hydrogel and Coating in Orthopaedic and Traumatology Surgery. Gels 2021; 7:126. [PMID: 34462412 PMCID: PMC8406094 DOI: 10.3390/gels7030126] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/20/2021] [Accepted: 08/23/2021] [Indexed: 01/23/2023] Open
Abstract
Implant related infection is one of the most frequent complications in orthopaedic and trauma surgery. Local antibiotic treatment strategies are becoming part of the prevention and treatment methodology for this fearful complication. To date, there are two coatings available on the market, both with a polylactic acid base. Current evidence supports the use of these types of coatings in the prophylaxis of periprosthetic infections and fracture-related infections. However, their therapeutic use has been less investigated. The purpose of this article is to summarise recent evidence relating to the clinical application of antibacterial hydrogels and coatings in orthopaedic and traumatology surgery and indicating which future applications may benefit from it.
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Affiliation(s)
- Daniele De Meo
- Orthopaedic and Traumatology Unit, Department of General Surgery, Plastic Surgery, Orthopedics, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro 3, 00185 Rome, Italy; (P.P.); (C.V.)
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
| | - Giancarlo Ceccarelli
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
- Department of Public Health and Infectious Diseases—Sapienza, University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy
| | - Giancarlo Iaiani
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
- Department of Public Health and Infectious Diseases—Sapienza, University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy
| | - Federico Lo Torto
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
- Plastic Surgery Unit, Department of General Surgery, Plastic Surgery, Orthopedics, Policlinico Umberto I Hospital—Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Diego Ribuffo
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
- Plastic Surgery Unit, Department of General Surgery, Plastic Surgery, Orthopedics, Policlinico Umberto I Hospital—Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Pietro Persiani
- Orthopaedic and Traumatology Unit, Department of General Surgery, Plastic Surgery, Orthopedics, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro 3, 00185 Rome, Italy; (P.P.); (C.V.)
| | - Ciro Villani
- Orthopaedic and Traumatology Unit, Department of General Surgery, Plastic Surgery, Orthopedics, Policlinico Umberto I Hospital—Sapienza, University of Rome, Piazzale A. Moro 3, 00185 Rome, Italy; (P.P.); (C.V.)
- M.I.T.O. (Infections in Traumatology and Orthopedics Surgery) Study Group, Policlinico Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy; (G.C.); (G.I.); (F.L.T.); (D.R.)
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Khalifa AA, Bakr HM, Farouk OA. Biomaterials and technologies in the management of periprosthetic infection after total hip arthroplasty: An updated review. JOURNAL OF MUSCULOSKELETAL SURGERY AND RESEARCH 2021; 5:142-151. [DOI: 10.25259/jmsr_51_2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Although total hip arthroplasty (THA) is considered one of the most efficacious procedures for managing various hip conditions, failures due to different mechanisms are still being reported. Periprosthetic joint infection (PJI) is one of the devastating causes of failure and revision of THA. PJI carries a burden on the patient, the surgeon, and the health-care system. The diagnosis and management of PJIs carry many morbidities and increased treatment costs. The development of PJI is multifactorial, including issues related to the patient’s general condition, the surgeon’s efficiency, surgical technique, and the implants used. Recent advances in the area of diagnosis and predicting PJI as well as introducing new technologies and biomaterials update for the prevention and treatment of PJI. Local implant coatings, advancement in the bearing surfaces technologies, and new technologies such as immunotherapy and bacteriophage therapy were introduced and suggested as contemporary PJI eradication solutions. In this review, we aimed at discussing some of the newly introduced materials and technologies for the sake of PJI control.
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Affiliation(s)
- Ahmed A. Khalifa
- Department of Orthopedics, Qena Faculty of Medicine and University Hospital, South Valley University, Qena, Egypt
| | - Hatem M. Bakr
- Department of Orthopedics and Traumatology, Assiut University Hospital, Assiut, Egypt,
| | - Osama A. Farouk
- Department of Orthopedics and Traumatology, Assiut University Hospital, Assiut, Egypt,
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Kanakaris NK, Giannoudis PV. Biofilm and its implications postfracture fixation: All I need to know. OTA Int 2021; 4:e107(1-7). [PMID: 37609478 PMCID: PMC10441677 DOI: 10.1097/oi9.0000000000000107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/10/2020] [Accepted: 12/11/2020] [Indexed: 08/24/2023]
Abstract
Biofilm represents an organized multicellular community of bacteria having a complex 3D structure, formed by bacterial cells and their self-produced extracellular matrix. It usually attaches to any foreign body or fixation implant. It acts as a physical protective barrier of the bacteria from the penetration of antibodies, bacteriophages, granulocytes and biocides, antiseptics, and antibiotics. Biofilm-related infections will increase in the near future. This group of surgical site infections is the most difficult to diagnose, to suppress, to eradicate, and in general to manage. Multispecialty teams involved in all stages of care are an effective way to improve results and save resources and time for the benefit of patients and the health system. Significant steps have occurred recently in the prevention and development of clever tools that we can employ in this everlasting fight with the bacteria. Herein, we attempt to describe the nature and role of the "biofilm" to the specific clinical setting of surgical site infections in the field of orthopaedic trauma surgery.
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Affiliation(s)
- Nikolaos K Kanakaris
- Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds
- NIHR Leeds Biomedical Research Center, Chapel Allerton Hospital, Leeds, United Kingdom
| | - Peter V Giannoudis
- Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds
- NIHR Leeds Biomedical Research Center, Chapel Allerton Hospital, Leeds, United Kingdom
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Eidmann A, Ewald A, Boelch SP, Rudert M, Holzapfel BM, Stratos I. In vitro evaluation of antibacterial efficacy of vancomycin-loaded suture tapes and cerclage wires. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:42. [PMID: 33825078 PMCID: PMC8024230 DOI: 10.1007/s10856-021-06513-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 03/16/2021] [Indexed: 05/10/2023]
Abstract
Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demonstrated increased bacterial growth inhibition when compared to NaCl-treated controls. Vancomycin-loaded tapes showed an additional twofold and eightfold increase of bacterial growth inhibition compared to vancomycin-loaded wires at day 1 and 2, respectively. Elution tests at day 1 revealed high levels of vancomycin concentration in vancomycin loaded tapes and wires. Additionally, the concentration in vancomycin loaded tapes was 14-fold higher when compared to vancomycin loaded wires. Incubating suture tapes and cerclage wires in vancomycin solution showed a good short-term antibacterial activity compared to controls. Considering the ease of vancomycin application on suture tapes or wires, our method could represent an attractive therapeutic strategy in biofilm prevention in orthopedic surgery.
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Affiliation(s)
- Annette Eidmann
- Department of Orthopaedic Surgery, Julius-Maximilians University Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany
| | - Andrea Ewald
- Department for Functional Materials in Medicine and Dentistry, University Hospital Wuerzburg, Pleicherwall 2, 97070, Wuerzburg, Germany
| | - Sebastian P Boelch
- Department of Orthopaedic Surgery, Julius-Maximilians University Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany
| | - Maximilian Rudert
- Department of Orthopaedic Surgery, Julius-Maximilians University Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany
| | - Boris M Holzapfel
- Department of Orthopaedic Surgery, Julius-Maximilians University Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany
| | - Ioannis Stratos
- Department of Orthopaedic Surgery, Julius-Maximilians University Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany.
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Grillo R, Pedrosa G, Teixeira RG. Protective hydrogel to heal post maxillofacial surgery paresthesia? ADVANCES IN ORAL AND MAXILLOFACIAL SURGERY 2021. [DOI: 10.1016/j.adoms.2021.100067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Chesnokov SA, Aleynik DY, Kovylin RS, Yudin VV, Egiazaryan TA, Egorikhina MN, Zaslavskaya MI, Rubtsova YP, Gusev SA, Mlyavykh SG, Fedushkin IL. Porous Polymer Scaffolds based on Cross-Linked Poly-EGDMA and PLA: Manufacture, Antibiotics Encapsulation, and In Vitro Study. Macromol Biosci 2021; 21:e2000402. [PMID: 33759338 DOI: 10.1002/mabi.202000402] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 02/11/2021] [Indexed: 11/10/2022]
Abstract
Porous polymer materials derived from poly(ethylene glycol dimethacrylate) (poly-EGDMA) and antibiotic containing polylactide (PLA) are obtained for the first time. Porous poly-EGDMA monoliths with a system of open interconnected pores are synthesized by a visible light-induced radical polymerization of EGDMA in the presence of 70 wt% of porogenic agent, e.g., 1-butanol, 1-hexanol, 1-octanol, or cyclohexanol. The porosity of the obtained polymers is 75-78%. A modal pore size depends on the nature of the porogen and varies from 0.5 µm (cyclohexanol) to 12 µm (1-butanol). The polymer matrix made with 1-butanol features the presence of pores ranging from 1 to 100 µm. The pore surface of poly-EGDMA matrices is inlayered with poly-D,L-lactide (Mn 23 × 103 Da, PDI 1.31). The PLA-modified poly-EGDMA retains a porous structure that is similar to the initial poly-EGDMA but with improved strength characteristics. The presence of antibiotic containing PLA ensures a high and continuous antibacterial activity of the hybrid polymeric material for 7 days. The nontoxicity of all the porous matrices studied makes them promising for clinical tests as osteoplastic materials.
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Affiliation(s)
- Sergey A Chesnokov
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation
| | - Diana Ya Aleynik
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation.,Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Federation, Minin and Pozharsky Square 10/1, Nizhny Novgorod, 603005, Russian Federation
| | - Roman S Kovylin
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation
| | - Vladimir V Yudin
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation
| | - Tatevik A Egiazaryan
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation
| | - Marfa N Egorikhina
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation.,Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Federation, Minin and Pozharsky Square 10/1, Nizhny Novgorod, 603005, Russian Federation
| | - Maya I Zaslavskaya
- Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Federation, Minin and Pozharsky Square 10/1, Nizhny Novgorod, 603005, Russian Federation
| | - Yulia P Rubtsova
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation.,Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Federation, Minin and Pozharsky Square 10/1, Nizhny Novgorod, 603005, Russian Federation
| | - Sergey A Gusev
- Institute for Physics of Microstructures of Russian Academy of Sciences, Academicheskaya 7, Afonino, Nizhny Novgorod, 603087, Russian Federation
| | - Sergey G Mlyavykh
- Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Federation, Minin and Pozharsky Square 10/1, Nizhny Novgorod, 603005, Russian Federation
| | - Igor L Fedushkin
- G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, Nizhny Novgorod, 603950, Russian Federation
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Nichol T, Callaghan J, Townsend R, Stockley I, Hatton PV, Le Maitre C, Smith TJ, Akid R. The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium. Bone Joint J 2021; 103-B:522-529. [PMID: 33641411 PMCID: PMC7954144 DOI: 10.1302/0301-620x.103b3.bjj-2020-0347.r1] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Aims The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529.
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Affiliation(s)
- Tim Nichol
- Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK
| | - Jill Callaghan
- School of Clinical Dentistry, University of Sheffield, Sheffield, UK
| | - Robert Townsend
- Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, UK
| | - Ian Stockley
- Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, UK
| | - Paul V Hatton
- School of Clinical Dentistry, University of Sheffield, Sheffield, UK
| | - Christine Le Maitre
- Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK
| | - Thomas John Smith
- Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK
| | - Robert Akid
- Department of Materials, University of Manchester, Manchester, UK
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Reconstruction of infected post-traumatic bone defects of the distal femur with the Compress Ⓡ implant. Preliminary results of a staged non-biological strategy. Injury 2021; 52:606-615. [PMID: 33066985 DOI: 10.1016/j.injury.2020.10.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 08/18/2020] [Accepted: 10/04/2020] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Infected post-traumatic distal femur defects remain a therapeutic challenge. Non-biological reconstruction offers an option for avoiding complex biological knee arthrodesis procedures. The CompressⓇ implant is an alternative to the traditional distal femur stemmed megaprosthesis. The aim of this study is to analyse the first patients treated with a distal femur CompressⓇ prosthesis to manage massive infected post-traumatic defects of the distal femur with joint involvement. METHODS We retrospectively reviewed all patients with massive infected defects of the distal femur where this implant was used in a two-stage strategy, together with an antibacterial coating hydrogel (DACⓇ). The specific protocol, microbiological data, clinical and radiological results, complications, functional results and prosthesis survivorship were determined. Follow-up was for a minimum of 12 months, or until implant removal. RESULTS Ten patients (11 CompressⓇ implants) with a mean age of 52 years (range 35-73) were included. On average, patients had undergone 4.4 previous surgical procedures before index surgery. The mean bone defect was 14 cm (range 8-21). After a median follow-up of 27 months (range 12-50 months) no patient had presented with recurrence of the infection, and limb salvage was achieved in all cases. Two patients suffered aseptic loosening which required revision of the femoral component. The short-term survivorship of the implant in our series was 81.8% at 4 years, with all failures occurring in the first 7 months. After this 7-month time threshold, we encountered no further loosening. Regarding functional outcomes, patients had a mean knee ROM of -4/86, expressed high overall satisfaction with the procedure according to the SAPS scale, and had an average LEFS of 52.5% (40-72.5%). CONCLUSION Non-biological reconstruction of the distal femur with the CompressⓇ implant is a valid option in selected patients with massive infected defects with joint involvement. Survivorship was high, with all loosening occurring in the first months after surgery-representing a failure in the osseointegration of the implant.
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Zoccali C, Scoccianti G, Biagini R, Daolio PA, Giardina FL, Campanacci DA. Antibacterial hydrogel coating in joint mega-prosthesis: results of a comparative series. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 2021; 31:1647-1655. [PMID: 33547509 DOI: 10.1007/s00590-021-02884-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE Joint mega-prosthesis after bone tumors, severe trauma or infection is associated with high rates of post-surgical septic complications. A fast-resorbable antibacterial hydrogel coating (DAC®, Defensive Antibacterial Coating) has previously been shown to be able to significantly reduce surgical site infection in various clinical settings. Aim of the present study was to evaluate the safety and efficacy of the DAC hydrogel coating to prevent early periprosthetic joint infection after joint mega-prosthesis. METHODS In this three-centers, case-control study, 43 patients, treated with an antibacterial hydrogel coated mega-prosthesis for oncological (N = 39) or non-oncological conditions (N = 4), were retrospectively compared with 43 matched controls, treated with mega-implants without the coating. Clinical, laboratory and radiographic examinations were performed to evaluate the occurrence of post-surgical infection, complications and adverse events. RESULTS At a mean follow-up of 2 years, no evidence of infection or adverse events were observed in the DAC-treated group, compared to six cases of post-surgical infection in the control group. CONCLUSION This matched case-control study shows that a fast-resorbable, antibiotic-loaded coating can be safely used to protect joint mega-prosthesis, providing a reduction of early surgical site infections with no side effects. Larger prospective trials with longer follow-ups are warranted to confirm this report. TRIAL REGISTRATION RS1229/19 (Regina Elena National Cancer Institute Experimental Registry Number).
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Affiliation(s)
- Carmine Zoccali
- Oncological Orthopedics Department, IFO - Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
| | - Guido Scoccianti
- Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla, 3, 50134, Florence, Italy
| | - Roberto Biagini
- Oncological Orthopedics Department, IFO - Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Primo Andrea Daolio
- Oncologic Surgery Centre, Gaetano Pini Orthopedic Institute, Via Quadronno, 25, 20122, Milan, Italy
| | - Fabio Luca Giardina
- Oncologic Surgery Centre, Gaetano Pini Orthopedic Institute, Via Quadronno, 25, 20122, Milan, Italy
| | - Domenico Andrea Campanacci
- Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla, 3, 50134, Florence, Italy
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Sun CK, Ke CJ, Lin YW, Lin FH, Tsai TH, Sun JS. Transglutaminase Cross-Linked Gelatin-Alginate-Antibacterial Hydrogel as the Drug Delivery-Coatings for Implant-Related Infections. Polymers (Basel) 2021; 13:polym13030414. [PMID: 33525449 PMCID: PMC7866112 DOI: 10.3390/polym13030414] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 01/17/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023] Open
Abstract
Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel; the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.
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Affiliation(s)
- Chung-Kai Sun
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan; or
| | - Cherng-Jyh Ke
- Biomaterials Translational Research Center, China Medical University Hospital, No. 2, Yude Rd., Taichung City 40447, Taiwan;
| | - Yi-Wen Lin
- Institute of Biomedical Engineering, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan; (Y.-W.L.); (F.-H.L.)
- Institute of Biomedical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan
| | - Feng-Huei Lin
- Institute of Biomedical Engineering, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan; (Y.-W.L.); (F.-H.L.)
- Institute of Biomedical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan
- Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan, Miaoli County 35053, Taiwan
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan; or
- Correspondence: (T.-H.T.); (J.-S.S.); Tel.: +886-2-2826-7115 (T.-H.T.); Fax: +886-2-2822-5044 (T.-H.T.)
| | - Jui-Sheng Sun
- Department of Orthopedic Surgery, College of Medicine, China Medical University, No. 2, Yu-Der Rd., Taichung City 40447, Taiwan
- Department of Orthopedic Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan
- Correspondence: (T.-H.T.); (J.-S.S.); Tel.: +886-2-2826-7115 (T.-H.T.); Fax: +886-2-2822-5044 (T.-H.T.)
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Verza BS, van den Beucken JJJP, Brandt JV, Jafelicci Junior M, Barão VAR, Piazza RD, Tagit O, Spolidorio DMP, Vergani CE, de Avila ED. A long-term controlled drug-delivery with anionic beta cyclodextrin complex in layer-by-layer coating for percutaneous implants devices. Carbohydr Polym 2021; 257:117604. [PMID: 33541637 DOI: 10.1016/j.carbpol.2020.117604] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/22/2020] [Accepted: 12/30/2020] [Indexed: 02/07/2023]
Abstract
This study demonstrated a drug-delivery system with anionic beta cyclodextrin (β-CD) complexes to retain tetracycline (TC) and control its release from multilayers of poly(acrylic acid) (PAA) and poly(l-lysine) (PLL) in a ten double layers ([PAA/PLL]10) coating onto titanium. The drug-delivery capacity of the multilayer system was proven by controlled drug release over 15 days and sustained released over 30 days. Qualitative images confirmed TC retention within the layer-by-layer (LbL) over 30 days of incubation. Antibacterial activity of TC/anionic β-CD released from the LbL was established against Staphylococcus aureus species. Remarkably, [PAA/PLL]10/TC/anionic β-CD antibacterial effect was sustained even after 30 days of incubation. The non-cytotoxic effect of the multilayer system revealed normal human gingival fibroblast growth. It is expected that this novel approach and the chemical concept to improve drug incorporation into the multilayer system will open up possibilities to make the drug release system more applicable to implantable percutaneous devices.
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Affiliation(s)
- Beatriz S Verza
- Department of Dental Materials and Prosthodontics, School of Dentistry at Araraquara, São Paulo State University (UNESP), Humaita, 1680 Araraquara, São Paulo, Brazil.
| | | | - João V Brandt
- Department of Physical Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, São Paulo 14801-970, Brazil.
| | - Miguel Jafelicci Junior
- Department of Physical Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, São Paulo 14801-970, Brazil.
| | - Valentim A R Barão
- Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901, Piracicaba, São Paulo 13414-903, Brazil.
| | - Rodolfo D Piazza
- Department of Physical Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, São Paulo 14801-970, Brazil.
| | - Oya Tagit
- Department of Tumor Immunology, Radboudumc and Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein Zuid, 28 Nijmegen, the Netherlands.
| | - Denise M P Spolidorio
- Department of Physiology and Pathology, School of Dentistry at Araraquara, São Paulo State University (UNESP), Araraquara, São Paulo 14801-903, Brazil.
| | - Carlos Eduardo Vergani
- Department of Dental Materials and Prosthodontics, School of Dentistry at Araraquara, São Paulo State University (UNESP), Humaita, 1680 Araraquara, São Paulo, Brazil.
| | - Erica D de Avila
- Department of Dental Materials and Prosthodontics, School of Dentistry at Araraquara, São Paulo State University (UNESP), Humaita, 1680 Araraquara, São Paulo, Brazil.
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Liu J, Qu S, Suo Z, Yang W. Functional hydrogel coatings. Natl Sci Rev 2020; 8:nwaa254. [PMID: 34691578 PMCID: PMC8288423 DOI: 10.1093/nsr/nwaa254] [Citation(s) in RCA: 156] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 09/22/2020] [Accepted: 09/23/2020] [Indexed: 12/21/2022] Open
Abstract
Hydrogels—natural or synthetic polymer networks that swell in water—can be made mechanically, chemically and electrically compatible with living tissues. There has been intense research and development of hydrogels for medical applications since the invention of hydrogel contact lenses in 1960. More recently, functional hydrogel coatings with controlled thickness and tough adhesion have been achieved on various substrates. Hydrogel-coated substrates combine the advantages of hydrogels, such as lubricity, biocompatibility and anti-biofouling properties, with the advantages of substrates, such as stiffness, toughness and strength. In this review, we focus on three aspects of functional hydrogel coatings: (i) applications and functions enabled by hydrogel coatings, (ii) methods of coating various substrates with different functional hydrogels with tough adhesion, and (iii) tests to evaluate the adhesion between functional hydrogel coatings and substrates. Conclusions and outlook are given at the end of this review.
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Affiliation(s)
- Junjie Liu
- Center for X-Mechanics, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province and Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China
- State Key Laboratory of Fluid Power and Mechatronic System, Zhejiang University, Hangzhou 310027, China
- Applied Mechanics and Structure Safety Key Laboratory of Sichuan Province, School of Mechanics and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Shaoxing Qu
- Center for X-Mechanics, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province and Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China
- State Key Laboratory of Fluid Power and Mechatronic System, Zhejiang University, Hangzhou 310027, China
| | - Zhigang Suo
- John A. Paulson School of Engineering and Applied Sciences, Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA 02138, USA
| | - Wei Yang
- Center for X-Mechanics, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province and Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China
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Franceschini M, Sandiford NA, Cerbone V, Araujo LCTD, Kendoff D. Defensive antibacterial coating in revision total hip arthroplasty: new concept and early experience. Hip Int 2020; 30:7-11. [PMID: 32907424 DOI: 10.1177/1120700020917125] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Infections remains the most feared complication in total hip arthroplasty (THA). New strategies of PJI prevention includes coating of conventional implants. Defensive Antibacterial Coating (DAC), an antibacterial hydrogel coating made of hyaluronan, poly-D and L-lactide can protect biomaterials as an effective barrier at the time of implantation. In addition, it can be used with topical antibiotics to prevent early colonisation of the implant. SCOPE This manuscript describes the detailed function of the DAC in general as well as an analysis of its use in revision THA in a series of 28 patients in a short-term follow-up.Its use in patients undergoing cementless re-implantation after 2-staged procedures in THA is described in detail within the manuscript. CONCLUSION DAC found to be effective in terms of infection control and safety in our patient cohort and has been expanded for cementless 1-staged revisions in PJI of the hip in our institution.
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Filipović U, Dahmane RG, Ghannouchi S, Zore A, Bohinc K. Bacterial adhesion on orthopedic implants. Adv Colloid Interface Sci 2020; 283:102228. [PMID: 32858407 DOI: 10.1016/j.cis.2020.102228] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 07/29/2020] [Accepted: 07/30/2020] [Indexed: 01/19/2023]
Abstract
Orthopedic implants are routinely used for fixation of fractures, correction of deformities, joint replacements, and soft tissue anchorage. Different biomaterials have been engineered for orthopedic implants. Previously, they were designed merely as mechanical devices, now new strategies to enhance bone healing and implant osteointegration via local delivery of molecules and via implant coatings are being developed. These biological coatings should enhance osteointegration and reduce foreign body response or infection. This article reviews current and future orthopedic implants, materials and surface characteristics, biocompatibility, and mechanisms of bacterial adhesion. Additionally, the review is addressing implant-related infection, the main strategies to prevent it and suggest possible future research that may control implant related-infection.
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Affiliation(s)
- Urška Filipović
- University Clinical Center of Ljubljana, Department of Traumatology, Zaloska 7, 1000 Ljubljana, Slovenia
| | - Raja Gošnak Dahmane
- University of Ljubljana, Faculty of Health Sciences, Zdravstvena pot 5, 1000 Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Institute of Anatomy, Korytkova 2, 1000 Ljubljana, Slovenia
| | | | - Anamarija Zore
- University of Ljubljana, Faculty of Health Sciences, Zdravstvena pot 5, 1000 Ljubljana, Slovenia
| | - Klemen Bohinc
- University of Ljubljana, Faculty of Health Sciences, Zdravstvena pot 5, 1000 Ljubljana, Slovenia.
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Ricciardi BF, Muthukrishnan G, Masters EA, Kaplan N, Daiss JL, Schwarz EM. New developments and future challenges in prevention, diagnosis, and treatment of prosthetic joint infection. J Orthop Res 2020; 38:1423-1435. [PMID: 31965585 PMCID: PMC7304545 DOI: 10.1002/jor.24595] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 01/03/2020] [Indexed: 02/04/2023]
Abstract
Prosthetic joint infection (PJI) is a devastating complication that results in substantial costs to society and patient morbidity. Advancements in our knowledge of this condition have focused on prevention, diagnosis, and treatment, in order to reduce rates of PJI and improve patient outcomes. Preventive measures such as optimization of patient comorbidities, and perioperative antibiotic usage are intensive areas of current clinical research to reduce the rate of PJI. Improved diagnostic tests such as synovial fluid (SF) α-defensin enzyme-linked immunosorbent assay, and nucleic acid-based tests for serum, SF, and tissue cultures, have improved diagnostic accuracy and organism identification. Increasing the diversity of available antibiotic therapy, immunotherapy, and alternative implant coatings remain promising treatments to improve infection eradication in the setting of PJI.
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Affiliation(s)
- Benjamin F Ricciardi
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Gowrishankar Muthukrishnan
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Elysia A Masters
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Nathan Kaplan
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - John L Daiss
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Edward M Schwarz
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
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