Date Published: March 08, 2018
Publisher: John Wiley and Sons Inc.
Author(s): Serena Rigo, Chao Cai, Gesine Gunkel‐Grabole, Lionel Maurizi, Xiaoyan Zhang, Jian Xu, Cornelia G. Palivan.
Microbial contamination and biofilm formation of medical devices is a major issue associated with medical complications and increased costs. Consequently, there is a growing need for novel strategies and exploitation of nanoscience‐based technologies to reduce the interaction of bacteria and microbes with synthetic surfaces. This article focuses on surfaces that are nanostructured, have functional coatings, and generate or release antimicrobial compounds, including “smart surfaces” producing antibiotics on demand. Key requirements for successful antimicrobial surfaces including biocompatibility, mechanical stability, durability, and efficiency are discussed and illustrated with examples of the recent literature. Various nanoscience‐based technologies are described along with new concepts, their advantages, and remaining open questions. Although at an early stage of research, nanoscience‐based strategies for creating antimicrobial surfaces have the advantage of acting at the molecular level, potentially making them more efficient under specific conditions. Moreover, the interface can be fine tuned and specific interactions that depend on the location of the device can be addressed. Finally, remaining important challenges are identified: improvement of the efficacy for long‐term use, extension of the application range to a large spectrum of bacteria, standardized evaluation assays, and combination of passive and active approaches in a single surface to produce multifunctional surfaces.
Surfaces in contact with biological fluids are prone to colonization with bacteria, which severely hamper their function and can cause infections and other unwanted side effects. Several types of medical implants and devices (i.e., catheters, tubes, artificial joints, etc.) are used in various parts of the body to replace the function of missing or disabled organs/joints or to facilitate tissue repair. For example, 17.5% of patients in European hospitals have a urinary catheter,1 and catheter‐associated urinary tract infections, often caused by Escherichia coli,2 are a common cause of secondary blood stream infections.1 Moreover, with the growth of an elderly population there is an increasing need for medical implant devices such as feeding‐ or tracheostomy tubes.3 Continued function of these implanted devices is a central aspect to improve the quality of life of patients; therefore, complications such as device‐associated infections (DAIs) are one of the most important challenges in this field. Bacteria can cause DAI if they colonize the device surface and grow into biofilms that induce a dynamic and multifaceted process, in which products like signaling molecules are actively shared and exchanged. The different states of biofilm formation include the transition of planktonic to sessile bacteria, attachment and cell‐to‐cell adhesion, growth and maturation, and detachment and dissolution to spread and colonize new areas. The microorganisms within a biofilm are embedded and protected by self‐produced extracellular polymeric substances (EPSs), which contain polysaccharides, proteins, extracellular DNA, glycoproteins, and other natural polymers. Treating DAI is difficult, because the bacteria in a biofilm are not easily accessible, the efficacy of antibiotic treatments is low due to their resistance to antibiotics4 and further reduced since concentration of the antibiotic below the minimal inhibitory concentration (MIC) even supports biofilm formation,5 thereby inducing ineffective treatment against nonmultidrug‐resistant bacteria strains, which tend to form more robust biofilms.6 Moreover, DAIs of orthopedic devices, which typically have low infection rates,7 are particularly difficult to treat. The device must be removed and replaced after disinfection of the infected area. Furthermore, replacement due to an infection is several times more costly than the primary implantation or replacement of a noninfected implant.8
In order to prevent biofilm formation on implanted devices, various substances and technological approaches have been proposed and tested that fulfill the specific constraints related to the production of devices with antibacterial surfaces. These requirements include easy and reproducible production,[[qv: 9a]] adequate sterilization,24 and possible repair without increasing the damage.25 Moreover, the several requirements have been identified that are essential for an efficient antimicrobial surface (Figure2), including specific properties and functionalities, which can change depending on the needed function and location of the aimed surface. In the following, current developments and importance of each of these parameters are highlighted.
Antimicrobial effects of surfaces can be evoked chemically, either the bulk material itself or the antimicrobial compounds embedded in it53 and by the surface architecture and topography.[[qv: 13b,54]] Different nanoscience‐based strategies have been developed to equip surfaces with antimicrobial or bacteria repelling activity: micro‐ and nanostructured surfaces, dynamic surfaces, coated surfaces, and surfaces that release active agents (Figure3).
In nature, surfaces that impede biofilm formation based on special compositions or topography have been discovered and inspired the development of synthetic antimicrobial surfaces with the tools of nanoscience. Active (bacteria killing) or passive (preventing bacteria attachment) strategies provide new solutions to effectively reduce DAI. Owing to the advances in nanoscience, smart surfaces that act in a special and time‐restricted area, and therefore able to lower doses and side effects were introduced. Moreover, an improved understanding of surface–microbe interactions at the micro‐ and nanoscale allows to engineer surfaces without any active agents needed, thereby eliminating side effects. In addition to conventional antibiotics, AMPs were recently introduced as an elegant approach that avoids both toxicity and bacterial resistance. However, there is still a long way to go in the development of effective, ecological, and economic antimicrobial surface strategies. Various antimicrobial surfaces with specific topography have been fabricated to obtain efficient and long‐term antifouling properties. Micro‐ and nanopatterns represent a passive approach and are generally less toxic than antibiotic‐releasing surfaces. However, most of the current fabrication methods for producing such patterns are still too complex and involve high costs. In addition, the domain of antimicrobial surfaces is still controversial due to the biocomplexity of the medical conditions and a lack of standardization of the characterization methods and functionality of such surfaces. Therefore, we limited our review to examples that support the first step of surface modification and indicated the advantages and limitations still to be solved but without details related to a specific application. A multitude of different medical applications for antibacterial and antimicrobial surfaces is evident; however, more recently new application areas have emerged, such as antimicrobial semiconductors on textile surfaces.114 It is clear that the biospecificity of the application is inducing supplementary requirements the functionalized surface should cope with, but they are not the focus of this review.
The authors declare no conflict of interest.