Surfaces Of Medical Devices Research Articles

Reducing bacteria and macrophage density on nanophase hydroxyapatite coated onto titanium surfaces without releasing pharmaceutical agents.

Reducing bacterial density on titanium implant surfaces has been a major concern because of the increasing number of nosocomial infections. Controlling the inflammatory response post implantation has also been an important issue for medical devices due to the detrimental effects of chronic inflammation on device performance. It has recently been demonstrated that manipulating medical device surface properties including chemistry, roughness and wettability can control both infection and inflammation. Here, we synthesized nanophase (that is, materials with one dimension in the nanoscale) hydroxyapatite coatings on titanium to reduce bacterial adhesion and inflammatory responses (as measured by macrophage functions) and compared such results to bare titanium and plasma sprayed hydroxyapatite titanium coated surfaces used clinically today. This approach is a pharmaceutical-free approach to inhibit infection and inflammation due to the detrimental side effects of any drug released in the body. Here, nanophase hydroxyapatite was synthesized in sizes ranging from 110-170 nm and was subsequently coated onto titanium samples using electrophoretic deposition. Results indicated that smaller nanoscale hydroxyapatite features on titanium surfaces alone decreased bacterial attachment in the presence of gram negative (P. aeruginosa), gram positive (S. aureus) and ampicillin resistant gram-negative (E. coli) bacteria as well as were able to control inflammatory responses; properties which should lead to their further investigation for improved medical applications.

Microbial biofilm formation on silicone nasal splints: optimal time for splint removal

Biofilms are sessile communities associated with persistent infections and are resistant to conventional therapeutic strategies. They survive on the surface of various inorganic medical devices and cause serious medical problems. We recruited 25 patients who underwent nasal surgery between January and May 2013. All patients received silicone splints at the conclusion of the procedure. Pieces of the splints were collected 48, 72 and 96 h post-surgery and prepared for scanning electron microscopy evaluation to assess biofilm formation. Biofilm was observed in 3, 14 and 25 of the 25 samples at 48, 72 and 96 h, respectively. The differences in the proportions of the samples with biofilm formation at each time point (48, 72, and 96 h) were statistically significant. Our data demonstrated that biofilm formation on silicone splints increases significantly after 48 h following placement. Although packing may reduce complications, surgeons must consider the potential hazards of packing materials, such as biofilm formation at 48 h post-surgery.

Microbial biofilm formation on silicone nasal splints: optimal time for splint removal.

Biofilms are sessile communities associated with persistent infections and are resistant to conventional therapeutic strategies. They survive on the surface of various inorganic medical devices and cause serious medical problems. We recruited 25 patients who underwent nasal surgery between January and May 2013. All patients received silicone splints at the conclusion of the procedure. Pieces of the splints were collected 48, 72 and 96 h post-surgery and prepared for scanning electron microscopy evaluation to assess biofilm formation. Biofilm was observed in 3, 14 and 25 of the 25 samples at 48, 72 and 96 h, respectively. The differences in the proportions of the samples with biofilm formation at each time point (48, 72, and 96 h) were statistically significant. Our data demonstrated that biofilm formation on silicone splints increases significantly after 48 h following placement. Although packing may reduce complications, surgeons must consider the potential hazards of packing materials, such as biofilm formation at 48 h post-surgery.

Assessing Collagen Nanoscale Thin Films Heterogeneity by AFM Multimode Imaging and Nanoindetation for NanoBioMedical Applications

Collagen due to its filamentous shape and unique properties is a very promising molecule for the development of nanostructures, scaffolds, cell culture platforms and nanobiomaterials. Furthermore, collagen thin films are of great interest as they can cover non-biological surfaces in medical devices and sensors so as to offer them biocompatibility. Since surface nanotopography and mechanical properties can influence cell-biomaterial interactions it is of crucial im- portance to nano-characterize collagen surface and heterogeneity. Nano-characterization can be performed with Atomic Force Microscopy (AFM), which operates in a variety of modes/techniques and can offer a wide range of information, from topography to mechanical properties. In this paper it was sought to gain insights of structural and mechanical hetero- geneity of collagen fibers in thin films by combining AFM multimode-imaging, including phase imaging, with quantita- tive measurements through nanoindentation. The results demonstrated that the overlap-gap regions on collagen fibers (D-periodicity) yield a significant phase contrast, due to different mechanical properties. In addition, phase contrast was also demonstrated in collagen 'kinks', which provides evidence that collagen fiber shell and core possess different properties. The mechanical heterogeneity of the collagen fibers in the kink areas was confirmed by AFM-nanoindentation and the obtained quantitative measurements. In addition, AFM multimode imaging performance was demonstrated on fibroblasts cultured on collagen thin films. The correlation between the heterogeneous structure and the mechanical properties of collagen fibers in thin films will enable the design and development of biomaterials and tissue scaffolds with improved properties.

Biomimetic ultra-bubble-repellent surfaces based on a self-organized honeycomb film.

The adhesion of bubbles underwater remains the greatest cause of malfunctions in applications such as microfluidics, medical devices and heat exchangers. There is therefore an emerging need for ultra-bubble-repellent surfaces. Inspired by fish scales, which show high bubble repellency due to their hydrophilic nature and surface microstructures, we propose a novel method for preparing ultra-bubble-repellent surfaces by the hydrophilic treatment of self-organized microstructures. When in contact with air bubbles underwater, the artificial hydrophilic microstructured surfaces had a higher contact angle and a lower adhesion force than a flat surface. The mechanism leading to these properties is also investigated. Our method for the fabrication of ultra-bubble-repellent, hydrophilic, microstructured surfaces is simple and cost-effective, opening the way for its application in artificial devices, such as the inner surfaces of tubes, medical devices, and heat exchangers.

Bacterial adherence and biofilm formation on medical implants: a review.

Biofilms are a complex group of microbial cells that adhere to the exopolysaccharide matrix present on the surface of medical devices. Biofilm-associated infections in the medical devices pose a serious problem to the public health and adversely affect the function of the device. Medical implants used in oral and orthopedic surgery are fabricated using alloys such as stainless steel and titanium. The biological behavior, such as osseointegration and its antibacterial activity, essentially depends on both the chemical composition and the morphology of the surface of the device. Surface treatment of medical implants by various physical and chemical techniques are attempted in order to improve their surface properties so as to facilitate bio-integration and prevent bacterial adhesion. The potential source of infection of the surrounding tissue and antimicrobial strategies are from bacteria adherent to or in a biofilm on the implant which should prevent both biofilm formation and tissue colonization. This article provides an overview of bacterial biofilm formation and methods adopted for the inhibition of bacterial adhesion on medical implants.

Grazing incidence angle based sensing approach integrated with fiber-optic Fourier transform infrared (FO-FTIR) spectroscopy for remote and label-free detection of medical device contaminations.

Contamination of medical devices has become a critical and prevalent public health safety concern since medical devices are being increasingly used in clinical practices for diagnostics, therapeutics and medical implants. The development of effective sensing methods for real-time detection of pathogenic contamination is needed to prevent and reduce the spread of infections to patients and the healthcare community. In this study, a hollow-core fiber-optic Fourier transform infrared spectroscopy methodology employing a grazing incidence angle based sensing approach (FO-FTIR-GIA) was developed for detection of various biochemical contaminants on medical device surfaces. We demonstrated the sensitivity of FO-FTIR-GIA sensing approach for non-contact and label-free detection of contaminants such as lipopolysaccharide from various surface materials relevant to medical device. The proposed sensing system can detect at a minimum loading concentration of approximately 0.7 μg/cm(2). The FO-FTIR-GIA has the potential for the detection of unwanted pathogen in real time.

Addressing the Inflammatory Response to Clinically Relevant Polymers by Manipulating the Host Response Using ITIM Domain-Containing Receptors.

Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPhα), and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials.

An average enumeration method of hyperspectral imaging data for quantitative evaluation of medical device surface contamination.

We propose a quantification method called Mapped Average Principal component analysis Score (MAPS) to enumerate the contamination coverage on common medical device surfaces. The method was adapted from conventional Principal Component Analysis (PCA) on non-overlapped regions of a full frame hyperspectral image to resolve the percentage of contamination from the substrate. The concept was proven by using a controlled contamination sample with artificial test soil and color simulating organic mixture, and was further validated using a bacterial system including biofilm on stainless steel surface. We also validate the results of MAPS with other statistical spectral analysis including Spectral Angle Mapper (SAM). The proposed method provides an alternative quantification method for hyperspectral imaging data, which can be easily implemented by basic PCA analysis.

Layers of ways to control drug release

Drug Delivery When people overuse antibiotics, microbes can develop resistance. In a setting such as a hospital, where bacteria may accumulate on the surfaces of medical devices, it is important to be able to administer antibiotics on demand, without overusing them. Zhuk et al. show how films made from tannic acid and one of three antibiotics can decrease antibiotic use. They created a film that does not release any antibiotic at a pH of 7.4, but which does release it when it is exposed to Staphylococcus epidermidis or Escherichia coli , which acidify their local environments. The release depends on the antibiotic used, the film fabrication method, and the overall thickness of the film, providing multiple ways to control antibiotic delivery. ACS Nano 10.1021/nn500674g (2014).

Improved antibacterial behavior of titanium surface with torularhodin–polypyrrole film

The problem of microorganisms attaching and proliferating on implants and medical devices surfaces is still attracting interest in developing research on different coatings based on antibacterial agents. The aim of this work is centered on modifying titanium (Ti) based implants surfaces through incorporation of a natural compound with antimicrobial effect, torularhodin (T), by means of a polypyrrole (PPy) film. This study tested the potential antimicrobial activity of the new coating against a range of standard bacterial strains: Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and Pseudomonas aeruginosa. The morphology, physical and electrochemical properties of the synthesized films were assessed by SEM, AFM, UV–Vis, FTIR and cyclic voltammetry. In addition, biocompatibility of this new coating was evaluated using L929 mouse fibroblast cells. The results showed that PPy–torularhodin composite film acts as a corrosion protective coating with antibacterial activity and it has no harmful effect on cell viability.

Influence of papain in biofilm formed by methicillin-resistant Staphylococcus epidermidis and methicillin-resistant Staphylococcus haemolyticus isolates

Methicillin-resistant Staphylococcus epidermidis (MRSE) and methicillin-resistant Staphylococcus haemolyticus (MRSHa) are important coagulase-negative staphylococci. They are often isolated from bacteremia in humans mainly due to their ability to form biofilm on the surfaces of medical devices. Papain is a complex mixture of proteolytic enzymes and peroxidases extracted from the latex of Carica papaya and it is recognized by accelerating the healing process of wounds. This study aimed to evaluate the ability of the MRSE and MRSHa isolates to produce biofilms. Besides this, the ability of papain to inhibit the formation of biofilms or to disrupt the ones already formed by those bacteria was analyzed. Thirty MRSHa and 30 MRSE were isolated from bacteremia and used in this study. It was observed that papain has ability to reduce biofilms formed by MRSE (p < 0.06) and by MRSHa (p = 0.0005). In addition, papain was able to disrupt mature biofilms made by MRSE (p = 0.014). No antibacterial activity of papain was observed for any isolates of MRSE and MRSHa tested. Papain has been demonstrated as a potential product for reducing biofilm.

Substrate independent silver nanoparticle based antibacterial coatings

Infections arising from bacterial adhesion and colonization on medical device surfaces are a significant healthcare problem. Silver based antibacterial coatings have attracted a great deal of attention as a potential solution. This paper reports on the development of a silver nanoparticles based antibacterial surface that can be applied to any type of material surface. The silver nanoparticles were surface engineered with a monolayer of 2-mercaptosuccinic acid, which facilitates the immobilization of the nanoparticles to the solid surface, and also reduces the rate of oxidation of the nanoparticles, extending the lifetime of the coatings. The coatings had excellent antibacterial efficacy against three clinically significant pathogenic bacteria i.e. Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa. Studies with primary human fibroblast cells showed that the coatings had no cytotoxicity in vitro. Innate immune studies in cultures of primary macrophages demonstrated that the coatings do not significantly alter the level of expression of pro-inflammatory cytokines or the adhesion and viability of these cells. Collectively, these coatings have an optimal combination of properties that make them attractive for deposition on medical device surfaces such as wound dressings, catheters and implants.

Use of Poly (ε-Lysine) Dendrons: A Strategy Targeting Bacterial Quorum Sensing and Biofilm Formation

Pseudomonas aeruginosa is recognised as a major aetiological agent of nosocomial infections, which are associated with multiple-antibiotic resistance. Among many of its important virulence factors is its ability to form biofilms on the surfaces of implantable medical devices and to produce toxic metabolites, pyocyanin, via an intercellular cell density-dependent signalling system of communication. In this study, poly (ε-lysine) dendrons composed of increasingly branching generations were synthesised, characterised, and examined for their effects on virulence factor production in P. aeruginosa. The results show that these hyperbranched poly (ε-lysine) dendrons, in particular the 3rd generation, can increase the efficacy of a conventional antibiotic, ciprofloxacin, and reduce pyocyanin production, with marginal effects on the rate of bacterial replication, suggesting that the observed effects are not due to dendron toxicity. Furthermore, dendron and ciprofloxacin coadministration was identified as the most effective strategy which highlights the potential of peptide-based dendrons as quorum sensing inhibitors.

English

Acinetobacter baumannii is an opportunistic pathogen responsible for nosocomial infections due to biofilm formation on the surface of implantable medical devices. Thirty (30) strains of A. baumannii were isolated from medical devices and tested for their ability to form a biofilm. The factors that may influence this process, such as the hydrophobicity of the bacterial wall, temperature, duration of implantation and the nature of the medical device, were also investigated. Strains were able to form a biofilm; however this process was more substantial at 30°C than at 37°C and was maximal after 96 h of incubation. Strains seem to adhere better to silicone and latex than to polyvinylchloride (PVC) and no apparent relationship was found between hydrophobicity and biofilm formation.   Key words: Acinetobacter baumannii, biofilm, medical devices.

Highly sensitive pyrogen detection on medical devices by the monocyte activation test

Pyrogens are components of microorganisms, like bacteria, viruses or fungi, which can induce a complex inflammatory response in the human body. Pyrogen contamination on medical devices prior operation is still critical and associated with severe complications for the patients. The aim of our study was to develop a reliable test, which allows detection of pyrogen contamination on the surface of medical devices. After in vitro pyrogen contamination of different medical devices and incubation in a rotation model, the human whole blood monocyte activation test (MAT), which is based on an IL-1β-specific ELISA, was employed. Our results show that when combining a modified MAT protocol and a dynamic incubation system, even smallest amounts of pyrogens can be directly detected on the surface of medical devices. Therefore, screening of medical devices prior clinical application using our novel assay, has the potential to significantly reduce complications associated with pyrogen-contaminated medical devices.

Antimicrobial activity of tigecycline alone or in combination with rifampin against Staphylococcus epidermidis in biofilm

Staphylococcus epidermidis is a commensal inhabitant of the healthy human skin, but in the recent years, it has been recognized as a nosocomial pathogen especially in immunocompromised patients. The pathogenesis of S. epidermidis is thought to be based on its capacity to form biofilms on the surface of medical devices, where bacterial cells may persist, protected from host defence and antimicrobial agents. Rifampin has been shown to be one of the most active antimicrobial agents in the eradication of the staphylococcal biofilm. However, this antibiotic should not be used in monotherapy. Therefore, one of the objectives of our research was to study the efficacy of the tigecycline/rifampin combination against methicillin-resistant S. epidermidis embedded in biofilms. Of the 80 clinically significant S. epidermidis isolates, 75 strains possess the ability to form a biofilm. These bacteria formed the biofilm via ica-dependent mechanisms. However, other biofilm-associated genes, including aap (encoding accumulation-associated protein) and bhp (coding cell wall-associated protein), were present in 85 and 29 % of isolates, respectively. The biofilm structures of S. epidermidis strains were also analyzed in confocal laser scanning microscopy (CLSM) and the obtained image demonstrated differences in their architecture. In vitro studies showed that the MIC value for tigecycline against S. epidermidis growing in the biofilm ranged from 0.125 to 2 μg/mL. Tigecycline in combination with rifampin demonstrated higher activity against bacteria embedded in biofilms than tigecycline alone.

Development of a Novel Zinc Oxide/Polyvinyl Chloride Nanocomposite Material for Medical Implant Applications

ABSTRACTIn hospitals and clinics worldwide, medical device surfaces have become a rapidly growing source of nosocomial infections. Almost immediately after adhering to a device surface, bacteria can begin to form a biofilm, which makes the infection especially difficult to treat and often necessitates device removal. Adding to the severity of this problem is the spread of bacterial genetic tolerance to antibiotics, in part demonstrated by the recent and significant increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA).Nanomaterials are beginning to be used for a wide variety of biomedical applications due to their unique surface properties which have the ability to control initial protein adsorption and subsequent cell behavior. This “nanoroughness” gives nanomaterials a greater functional surface area than conventional materials, which do not have significant features on the nanoscale. In addition, it is theorized that nanoparticles may also have general mechanisms of toxicity towards bacteria that do not cause problems for mammalian cells.The objective of the present in vitro study was to develop a nanocomposite material by embedding conventional polyvinyl chloride (PVC) with zinc oxide nanoparticles through a simple and inexpensive procedure. The effect of different nanoparticle sizes and %wts were investigated. Results demonstrated that this technique significantly decreased S. aureus density and biofilm formation without the incorporation of antibiotics or other pharmaceuticals, as well as increased the adhesion of human fibroblast cells. Thus, this material could have much promise for use in the manufacture of common implanted medical devices.

Development of a Skin-Like Tactile Sensor Array for Curved Surface

In this paper, we develop a skin-like tactile sensor array to measure the contact pressure of curved surfaces. The sensor array is laminated into a thin film 3 mm in thickness and can easily be wrapped around a pencil without damaging its skin-like structure. So far, we have achieved the array containing 8 × 16 sensor elements. Its spatial resolution is 1 element per 9 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> area and it can measure the pressure up to 360 kPa. The sensor-array patch contains three layers. The upper and lower layers are polydimethylsiloxane (PDMS) thin films embedded with the conductor strips formed by PDMS-based silver nanowires (AgNWs) networks. The middle layer is formed by the mixing of nickel powder with liquid PDMS for contact force measurement. Experimental tests have demonstrated that conductor strips on the upper layer can maintain their resistances ~ 23 Ω with increase when the tensile strain is up to 50%. Noted is the conductor made with carbon nanotubes can keep its conductivity unchanged for up to only 40% tensile strain. Through fatigue tests, it is observed that the measured AgNWs/PDMS conductor strip exhibits low and stable resistances. This is one of the most desired behaviors of the stretchable interconnects for signal transmission. The integrated sensor system can successfully measure the contact pressure induced by objects of different shapes. It can be applied on curved or non-planar surfaces in robots or medical devices for force detection and feedback.

Antibacterial Efficacy and Cytotoxicity of Silver Nanoparticle Based Coatings Facilitated by a Plasma Polymer Interlayer

Antibacterial coatings have been accepted as a potent solution to the problem of medical-device-associated infections, which affect millions of patients worldwide. In this work, we present silver-nanoparticle-based antibacterial coatings that are highly potent against medi- cally relevant bacteria such as S. epidermidis and S. aureus but do not have apparent cytotoxicity to primary human fibroblast cells. The silver nanoparticles used in the coatings are synthesized in the presence of trisodium citrate. At a given moment, 2-mercaptosuccinc acid is added to allow for reduction of nanoparticle size and to provide the well-defined surface architecture necessary for controllable surface immobilization. Important for application, the technology is facilitated by a functional-plasma-deposited polymer interlayer. This makes it applicable to the surface of medical devices manufactured from any type of material.