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WIREs Nanomed Nanobiotechnol
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Coatings and surface modifications imparting antimicrobial activity to orthopedic implants

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Bacterial colonization and biofilm formation on an orthopedic implant surface is one of the worst possible outcomes of orthopedic intervention in terms of both patient prognosis and healthcare costs. Making the problem even more vexing is the fact that infections are often caused by events beyond the control of the operating surgeon and may manifest weeks to months after the initial surgery. Herein, we review the costs and consequences of implant infection as well as the methods of prevention and management. In particular, we focus on coatings and other forms of implant surface modification in a manner that imparts some antimicrobial benefit to the implant device. Such coatings can be classified generally based on their mode of action: surface adhesion prevention, bactericidal, antimicrobial‐eluting, osseointegration promotion, and combinations of the above. Despite several advances in the efficacy of these antimicrobial methods, a remaining major challenge is ensuring retention of the antimicrobial activity over a period of months to years postoperation, an issue that has so far been inadequately addressed. Finally, we provide an overview of additional figures of merit that will determine whether a given antimicrobial surface modification warrants adoption for clinical use. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants
A pictographic representation of the steps in bacterial biofilm formation using a Pseudomonas aeruginosa case study. (a) Bacteria adhere loosely and reversibly to the surface by non‐specific binding. (b) Bacteria attach irreversibly to the surface and begin forming cell clusters. (c) Accumulation—Multiple layers of bacteria form and EPS layer provides protection to bacterial community. (d) Maturation—Biofilm reaches maximum thickness and cells communicate via quorum sensing. and (e) Dispersion—Clusters detach and infection spreads to new areas. (Reprinted with permission from Ref 17. Copyright 2003 Nature Publishing Group)
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Enhanced antimicrobial activity using ionic liquids. (a) Schematic showing antimicrobial effect of porous sol–gel coating incorporating a silver ion (Ag+)‐generating ‘ionosol’ on Escherichia coli cells. (b) Cross‐sectional scanning electron microscope (SEM) images of the antimicrobial coatings revealing porous structure throughout the coating. (Reprinted with permission from Ref 117. Copyright 2012 American Chemical Society)
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Schematic illustrating bactericidal processes for Escherichia coli cells on Cu/TiO2 thin film under weak UV light irradiation. (a) E. coli cell membranes are shown. (b) Reactive species generated by the TiO2 photocatalyst attack and open the outer membrane. (c) Cu ions effectively penetrate into the cell cytoplasmic membrane, resulting in cell lysis. (Reprinted with permission from Ref 53. Copyright 2003 American Chemical Society)
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Examples of grafting polymers onto substrates resulting in prevention of bacterial adhesion on the surfaces. (a) A substrate modified by grafting‐to approach in which the initially adsorbed polymer impedes further deposition, resulting in a low density of brushes. (b) Modification of a substrate by grafting‐from approach in which an initiator‐bearing substrate is exposed to monomer to afford thick, dense polymer brushes. (c) Schematic of grafting poly(SPMA) on the three‐dimensional (3D) printed structures: to initiate atom transfer radical polymerization (ATRP), the Br‐containing vinyl‐terminated initiator [2‐(2‐bromoisobutyryloxy)ethyl methacrylate (BrMA)] was premixed with the resin consisting of acrylate‐based prepolymers, cross‐linking agents, and a phosphine oxide‐based photoinitiator. The acrylate‐terminated polymers were utilized to incorporate with the initiator to achieve covalent bonding and BrMA was used without affecting the photopolymerization during three‐dimensional (3D) printing processes. (a, b: Reprinted with permission from Ref 108. Copyright 2009 American Vacuum Society, c: Reprinted with permission from Ref 50. Copyright 2013 Royal Society of Chemistry)
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Schematic representation of multilayer biodegradable films produced by a layer‐by‐layer deposition method. Multiple layers of (heparin/chitosan) − (polyvinylpyrrolidone/poly(acrylic acid))x [(HEP/CHI)x − (PVP/PAA)x], where ‘x’ denotes number of layers, are constructed based on electrostatic interaction for HEP/CHI and hydrogen bond interaction for PVP/PAA, followed by thermal treatment at 110°C for 16 h for crosslinking to form anhydride groups. In simulated physiological condition (e.g., PBS buffer at 37°C), (PVP/PAA)10 layers were degradable in 24 h, leading to almost no bacterial adhesion. After degradation of (PVP/PAA) layers, the underlying (HEP/CHI)x layers displayed contact killing of bacteria. (Reprinted with permission from Ref 48. Copyright 2013 American Chemical Society)
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A schematic illustrating the various modes of action of different coatings and surface modifications. (a) Prevention of bacterial adhesion is possible due to physical actions like presence of polymer brush. (b) Prevention of bacterial adhesion due to the presence of a sacrificial layer which do not allow the bacteria to adhere to the surface. (c) Killing of bacteria due to the release of antimicrobial agents to the surrounding regions. (d) Killing of adherent bacteria due to the presence of antimicrobial agents present on the surface. (e) Promotion and acceleration of desired cells which compete with the bacteria to promote osseointegration and prevent colonization.
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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