Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections
Abstract
:1. Introduction
2. Etiopathology
- (1)
- Attachment. Microorganisms come into contact with the surface, a process that is at least partly stochastic, driven by physical and chemical forces [25,26,27]. Furthermore, host proteins rapidly coat the surface of medical devices, facilitating specific adhesion mediated by microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), which are part of the surface of many bacteria, e.g., Staphylococcus spp. [28,29].
- (2)
- Maturation is characterized by intercellular aggregation coupled to a variety of molecules such as proteins or, usually, exopolysaccharides of a polysaccharide nature, and structuring forces that rearrange the biofilm into three-dimensional structures of variable morphology depending on the species and with microchannels within them [28]. During this stage, one of the most important processes is the production of the exopolysaccharide matrix, whose composition is characteristic of each species, and even of each strain [28,29,30,31]. At this stage, the relatively simple structure that the pre-biofilm acquired in irreversible adhesion takes on a much more structurally complex three-dimensional organization [32]. The nutritional gradient inside the biofilm gives rise to a variety of cells with metabolic differences, including starved cells, dormant cells, viable non-cultivable cells, “persister” cells, and dead cells [27,33].
- (3)
- Dispersal. This is the process by which mature biofilm cells disperse to adjacent areas passively or actively [23,27]. Through this stage, the infection spreads to adjacent niches in an environment or within the host once nutrients or space has been depleted [32], where it attaches again and restarts the cycle.
3. Conventional Prevention of Prosthetic Joint Infections
4. Local Preventive Antibiotic-Based Strategies
4.1. Active Titanium Surfaces Loaded with Antibiotics
4.2. Coating Loaded with Antibiotic for Titanium Alloys
4.3. The Antibiotic of Choice for Local Antibiotic-Based Therapy
5. Local Preventive Heavy Metals-Based Strategies
6. Limitations Associated with Local PJI Prevention
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Year | Type of Surface Modification | Bacteria Evaluated | Bacterial State | Cytotoxicity (%) | Level Study | Cell Lines/Animal Used In Vivo | Reference |
---|---|---|---|---|---|---|---|
2014 | Gentamicin-loaded nanotubes with different diameters | SA, SE | Biofilm | ND | In vitro | hBMMS cells | [71] |
2016 | Chitosan-coated gentamicin-loaded nanotubes | SA | Planktonic | 20 | In vitro | MG-63 osteoblasts | [72] |
2017 | Gentamicin-loaded nanotubes made with anodization | SA | Biofilm | ND | In vivo | ‒/rabbit | [73] |
2018 | Chitosan-hyaluronic acid-coated vancomycin-loaded nanotubes | SA | Planktonic/Biofilm | 0 | In vitro/in vivo | Primary osteoblasts/rat | [74] |
Vancomycin-loaded micro-patterning | MRSA | Biofilm | ND | In vivo | ‒/rabbit | [75] | |
Gentamicin and/or vancomycin F-dopped nanotubes | SA, SE, EC | Planktonic | ND | In vitro | ‒/‒ | [66] | |
2019 | Gentamicin plus vancomycin F- and P-dopped bottle-shaped nanotubes | SA | Biofilm | 0 | In vitro/in vivo | MC3T3-E1 osteoblasts/rabbit | [76] |
Year | Antibiotic Covalently Bound | Bacteria Evaluated | Bacterial State | Cytotoxicity (%) | Level Study | Cell Lines/Animal Used In Vivo | Reference |
---|---|---|---|---|---|---|---|
2010 | Daptomycin | SA | Biofilm | ND | In vitro | ‒/‒ | [90] |
2014 | Doxycycline | ‒ | ‒ | 0− <40 | In vitro/in vivo | MC3T3-E1 osteoblasts/rabbit | [85] |
2015 | Ciprofloxacin | PA | Biofilm | 0 | In vitro/in vivo | NIH3T3 fibroblasts/mouse | [84] |
2016 | Vancomycin/caspofungin | SA, CA | Biofilm | 0 | In vitro/in vivo | hME cells/rat | [86] |
SPI031 | SA, PA | Biofilm | 0 | In vitro/in vivo | hBMMS cells, hME cells/mouse | [89] | |
Enoxacin | MRSA, SE, EC | Planktonic, Biofilm | 0 | In vitro/in vivo | hBMMS cells/rat | [87] | |
2017 | Bacitracin | SA | Biofilm | ND | In vivo | ‒/rat | [88] |
Year | Type of Coating | Evaluated Bacteria | Bacterial State | Cytotoxicity (%) | Level Study | Cell Lines/Animal Used In Vivo | Reference |
---|---|---|---|---|---|---|---|
2010 | Vancomycin-loaded PMMA | SE | Biofilm | ND | In vitro | ‒/‒ | [91] |
Inorganic sol–gel with Polymyxin B covalently bound | EC | Planktonic | ND | In vitro | ‒/‒ | [92] | |
Gentamicin-loaded polyelectrolyte multilayer | SA | Planktonic, Biofilm | 0–80 | In vitro/in vivo | MC3T3-E1 osteoblasts/rabbit | [93] | |
2014 | Rifampicin and fosfomycin-loaded Hydroxyapatite coating | MSSA, MRSA | Biofilm | ND | In vivo | ‒/rabbit | [94] |
Ciprofloxacin-loaded chitosan-nanoparticles coating | SA | Planktonic | <30 | In vitro | MG63 osteoblast-like cells | [95] | |
Chitosan–vancomycin composite coatings | SA | Planktonic | 0 | In vitro | MG63 osteoblast-like cells | [96] | |
Vancomycin-loaded PLGA-coating | SA | Planktonic/Biofilm | 0 | In vitro | MC3T3-E1 osteoblasts/rabbit | [97] | |
2015 | Doxycycline-loaded polymer-lipid encapsulation matrix coating | MSSA, MRSA | Planktonic, Biofilm | ND | In vitro/in vivo | ‒/mouse | [98] |
2015 | PLGA-gentamicin-hydroxyapatite-coating | SA, SE | Planktonic, Biofilm | ND | In vitro/in vivo | ‒/rabbit | [99] |
2016 | Gentamicin-derivates coating | SA | Biofilm | ND | In vivo | ‒/rats | [100] |
2016 | Vancomycin-loaded phosphatidyl-choline | SA | Biofilm | ND | In vivo | ‒/rabbit | [101] |
2016 | Tetracycline loaded chitosan-gelatin nanosphere coating | SA | Biofilm | >90 | In vitro/in vivo | MC3T3-E1 osteoblasts/rabbit | [102] |
2017 | Doxycycline-loaded coaxial PCL-PVA nanofiber coating | SA | Biofilm | ND | In vivo | ‒/rat | [103] |
Tobramycin-loaded PDLLA coating | SA | Biofilm | ND | In vivo | ‒/rabbit | [1] | |
2018 | Vancomycin-loaded mesoporous bioglass-PLGA coating | SA | Planktonic, Biofilm | 0 | In vitro | hBMMS cells | [104] |
Vancomycin-loaded mesoporous silica nanoparticles-containing gelatin coating | SA | Biofilm | 0 | In vitro | hBMMS cells | [105] | |
2019 | Gentamicin-loaded polyelectrolyte multilayer | SA, SE | Planktonic, Biofilm | <5 | In vitro/in vivo | MC3T3-E1 osteoblast/rats | [106] |
Tobramycin-loaded hydroxyapatite coating | SA | Planktonic, Biofilm | ND | In vitro/in vivo | Endothelial cells, primary osteoblasts/rabbit | [107] | |
Vancomycin plus tigecycline-loaded PEG-PPS coating | SA | Biofilm | ND | In vivo | ‒/mouse | [108] | |
Gentamicin-loaded calcium phosphate-based coating | SA | Biofilm | ND | In vivo | ‒/rat | [109] | |
Vancomycin-loaded polymethacrylate coating | SA | Planktonic/Biofilm | ND | In vitro/in vivo | ‒/mouse | [110] | |
2020 | Cephalexin- and VEGF-loaded agarose-nanocrystalline apatite coating | SA | Planktonic | 0 | In vitro | MC3T3-E1 osteoblast | [111] |
Moxifloxacin-loaded organic-inorganic sol–gel | SA, SE, EC | Planktonic, Biofilm | 0 | In vitro/in vivo | MC3T3-E1 osteoblasts/mouse | [112] | |
Gentamicin loaded autologous blood glue | PA | Planktonic, Biofilm | 0 | In vitro | hBMMS cells | [113] | |
Fluconazole/anidulafungin-loaded organic-inorganic sol–gel | CA, CP | Planktonic, Biofilm | 0 | In vitro | MC3T3-E1 osteoblasts | [114] | |
Anidulafungin-loaded organic-inorganic sol–gel | CA | Biofilm | - | In vivo | ‒/mouse | [115] | |
Vancomycin-loaded starch coating | SA | Planktonic | ND | In vitro | ‒/‒ | [116] |
Year | Type of Surface Modification | Incorporated Metal | Metal Incorporation | Bacteria Evaluated | Bacterial State | Cytotoxicity (%) | Level Study | Cell Lines/Animal Used In Vivo | Reference |
---|---|---|---|---|---|---|---|---|---|
2009 | Metallurgical addition | Cu | Forge | SA, EC | Planktonic/biofilm | Ctyocompatible | In vitro/ in vivo | V79 cell line/rabbits | [148] |
2010 | Co-sputtering | Cu-Mn-O, Ag-Mn-O | ternary and quaternary oxides | SA, SE | Planktonic | - | In vitro | - | [149] |
Single step silver plasma immersion ion implantation | Ag | Nanoparticles | SA, EC | Planktonic | Cytocompatible | In vitro | MG63 human osteoblast-like cells | [150] | |
2011 | TiO2-chitosan/heparin coating | Ag | Nanoparticles | SA | Biofilm | - | In vivo | - | [151] |
Hydroxyapatite coating | Ag | Nanoparticles | EC | Planktonic | - | In vitro | - | [152] | |
2013 | Metallurgical addition | Cu | Powder metallurgy | SA, EC | Planktonic | - | In vitro | - | [153] |
Titanium nanotubular | Ag | Nanoparticle loading | SA, EC | Planktonic | - | In vitro | - | [154] | |
Polydopamine-modified alloy surface | Ag | Silver inonic inmobilization | EC | Planktonic | - | In vitro | - | [155] | |
Poly(ethylene glycol diacrylate)-co-acrylic acid coating | Ag | Nanoparticles | SA, EC, PA | Planktonic | Cytocompatible | In vitro | MG63 human osteoblast-like cells | [156] | |
2014 | Metallurgical addition | Cu | Powder metallurgy | SA, EC | Planktonic | - | In vitro | - | [157] |
Metallurgical addition | Cu | Casting with post-treatment | SA, EC | Planktonic | Cytocompatible | In vitro | L929 cell line | [158] | |
BMP-2/heparinchitosan-hydroxyapatite coating | Ag | Nanoparticles | SE, EC | Planktonic | Cytocompatible | In vitro | MC3T3-E1 cells, BMS cells | [159] | |
Aminosilanized titanium alloy | Ag | Nanoparticles | SA | Planktonic | - | In vitro | - | [160] | |
2016 | Metallurgical addition | Ag | Sintering | SA | Planktonic | - | In vitro | - | [161] |
2017 | Metallurgical addition | Ag | Sintering, casting, casting with appropiate post-treatment w/o surface tretament | SA | Planktonic | Cytocompatible | In vitro | MC3T3-E1 cells | [162] |
2018 | Metallurgical addition | Cu | Powder metallurgy | SA, EC | Planktonic | Cytocompatible | In vitro | HeLa cells | [163] |
Metallurgical addition | Ag | Spark plasma sintering and acid etching | SA | Planktonic | Cytocompatible | In vitro | MC3T3-E1 cells | [164] | |
Metallurgical addition | Cu | Casting with post-treatment | SA | Planktonic | - | In vitro | - | [165] | |
2019 | Metallurgical addition | Cu | Sintering | SA | Biofilm | - | In vivo | - | [166] |
Metallurgical addition | Ga | Powder metallurgy | MRSA | Planktonic/biofilm | Cytocompatible | In vitro | ATCC CRL-11372 and ATCC HTB-96 | [167] | |
2020 | Metallurgical addition | Cu | Microwave sintering | SA, EC | Planktonic | - | In vitro | - | [168] |
Metallurgical addition | Cu | Powder metallurgy | EC | Planktonic | - | In vitro | - | [169] | |
Metallurgical addition | Ag | Casting with appropiate post-treatment w/o surface tretament | SA | Planktonic | Cytocompatible | In vitro | MC3T3-E1 cells | [170] | |
2021 | Metallurgical addition | Cu | As-cast | SA | Biofilm | - | In vitro/in vivo | Mouse | [171] |
Metallurgical addition | Cu | As-cast | MRSA | Planktonic/biofilm | Cytocompatible | In vitro/in vivo | MC3T3-E1 cells/rat | [172] |
Preventive Approach of PJI | Advantages | Disadvantages |
---|---|---|
Antibiotic-based strategies | ||
Nanostructured titanium surfaces | Possibility of increasing the osteointegration of the titanium surfaces | Reduced durability of antibiotic protection |
Unknown biomechanical stability | ||
Loaded antibiotic can act against both bacteria directly adhered on the titanium surface and bacteria near but not in contact with it | Unknown effects on the useful life of the implant, osteointegration, and coagulation profile | |
Impossibility of intra-operative antibiotic load No clinical trials to support their use | ||
Antibiotics covalently bound to titanium surfaces | Long durability of antibiotic protection, up to months or years | Loaded antibiotic can only act against bacteria directly adhered on the titanium surface |
Unknown durability of antibiotic protection | ||
Impossibility of intra-operative antibiotic load | ||
No clinical trials to support their use | ||
Coatings loaded with antibiotic for titanium alloys | Possibility of increasing the osteointegration of the titanium surfaces | Incomplete surface protection |
Loaded antibiotic can act against both bacteria directly adhered on the titanium surface and bacteria near but not in contact with it | Unknown effects on the useful life of the implant, osteointegration, and coagulation profile | |
Possibility of intra-operative antibiotic load | ||
Clinical trials to support their use | Clinical trials that support their use has been carried out with few antibiotics | |
Heavy metals-based strategies | Broad spectrum antimicrobial effect (beyond antibacterial effect) | Local and systemic toxicity supported by clinical trials |
Loaded metals can act against both microorganisms directly adhered on the titanium surface and those near but not in contact with it | ||
Long durability | ||
Clinical trials to support their use |
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Esteban, J.; Vallet-Regí, M.; Aguilera-Correa, J.J. Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections. Antibiotics 2021, 10, 1270. https://doi.org/10.3390/antibiotics10101270
Esteban J, Vallet-Regí M, Aguilera-Correa JJ. Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections. Antibiotics. 2021; 10(10):1270. https://doi.org/10.3390/antibiotics10101270
Chicago/Turabian StyleEsteban, Jaime, María Vallet-Regí, and John J. Aguilera-Correa. 2021. "Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections" Antibiotics 10, no. 10: 1270. https://doi.org/10.3390/antibiotics10101270
APA StyleEsteban, J., Vallet-Regí, M., & Aguilera-Correa, J. J. (2021). Antibiotics- and Heavy Metals-Based Titanium Alloy Surface Modifications for Local Prosthetic Joint Infections. Antibiotics, 10(10), 1270. https://doi.org/10.3390/antibiotics10101270