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Plasma polymers from glycidol vapors are of interest for direct covalent grafting of molecules bearing amine or thiol groups. The question of whether pulsed plasma operation might lead to a higher surface density of epoxide groups and a higher density of grafted molecules is studied using the antifungal drug caspofungin. X‐ray photoelectron spectroscopy and Time of flight‐secondary ions mass spectrometry analysis followed by caspofungin grafting revealed that both continuous wave and pulsed plasmas led to surface epoxides but with higher densities upon pulsing. Investigations into stability suggested that glycidol plasma polymer coatings were still able to immobilize caspofungin after 2 years of storage, making them suitable for applications where grafting of molecules needs to be done immediately before usage of a device. [ABSTRACT FROM AUTHOR]

Plasma polymers have long been of interest as thin film coatings on biomedical devices and products, to generate desirable surface properties for favorable bio‐interfacial interactions. Plasma polymers have also been used as platforms for the covalent immobilization of bioactive molecules. More recently, additional aspects have been investigated, such as selective prevention of adhesion of microbial pathogens, either via plasma polymers per se or including antimicrobial drugs. Plasma polymers have also been investigated for the release of silver ions and small organic molecules. Complementing low‐pressure plasma approaches, processes at atmospheric pressure have attracted interest recently, including for nano/biocomposite coatings. This contribution reviews the use of plasma polymers for intended biomedical applications, with a focus on more recent topic areas. [ABSTRACT FROM AUTHOR]

Stimuli-responsive materials show considerable promise for applications that require control over biomolecule interactions at solid material interfaces. Graft coatings of poly(N-isopropylacrylamide) (pNIPAM) are of interest for biomedical and biotechnological applications due to their temperature-dependent switching of surface properties between adhesive and nonadhesive slates for cells and proteins. The characterization of protein adsorption to these switchable coatings is a formidable task since switching not only influences file affinity for proteins but at the same time induces a significant change in the coating. Here, the highly sensitive analytical technique of llme-of-flight-secondary ion mass spectrometry (TOFSIMS) combined with principal component analysis (PCA) was used for the characterization of protein adsorption onto pNIPAM coatings prepared by free radical polymerization onto-bound polymerlzable groups. Adsorption of bovine serum albumin and lysozyme onto pNIPAM coatings from phosphate buffered solutions was investigated at temperatures above and below the polymer's lower critical solution temperature (LCST). Below the LCST, no adsorbed proteins could be detected even with this ultrasensitive method. Whereas above the LCST, adsorbed protein was detected in amounts corresponding at less than the monolayer. PCA loadings plots showed that adventitious contaminants, which might lead to confounding or misleading spectral changes upon protein exposure, were not observed.

Cardiovascular disease is a leading cause of death worldwide; however, despite substantial advances in medical device surface modifications, no synthetic coatings have so far matched the native endothelium as the optimal hemocompatible surface for blood-contacting implants. A promising strategy for rapid restoration of the endothelium on blood-contacting biomedical devices entails attracting circulating endothelial cells or their progenitors, via immobilized cell-capture molecules; for example, anti-CD34 antibody to attract CD34+ endothelial colony-forming cells (ECFCs). Inherent is the assumption that the cells attracted to the biomaterial surface are bound exclusively via a specific CD34 binding. However, serum proteins might adsorb in-between or on the top of antibody molecules and attract ECFCs via other binding mechanisms. Here, we studied whether a surface with immobilized anti-CD34 antibodies attracts ECFCs via a specific CD34 binding or a nonspecific (non-CD34) binding. To minimize serum protein adsorption, a fouling-resistant layer of hyperbranched polyglycerol (HPG) was used as a "blank slate," onto which anti-CD34 antibodies were immobilized via aldehyde-amine coupling reaction after oxidation of terminal diols to aldehydes. An isotype antibody, mIgG1, was surface-immobilized analogously and was used as the control for antigen-binding specificity. Cell binding was also measured on the HPG hydrogel layer before and after oxidation. The surface analysis methods, x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, were used to verify the intended surface chemistries and revealed that the surface coverage of antibodies was sparse, yet the anti-CD34 antibody grafted surface-bound ECFCs very effectively. Moreover, it still captured the ECFCs after BSA passivation. However, cells also attached to oxidized HPG and immobilized mIgG1, though in much lower amounts. While our results confirm the effectiveness of attracting ECFCs via surface-bound anti-CD34 antibodies, our observation of a nonspecific binding component highlights the importance of considering its consequences in future studies. [ABSTRACT FROM AUTHOR]

Furanone compounds (fimbrolides) have attracted interest as antibacterial compounds for use in human health care, for instance, as an antibacterial coating for medical devices to combat device-centered infections. To ensure effectiveness for extended periods of time, they must be immobilized covalently onto a device surface; in this study, this was done via azide/nitrene chemistry and photochemical coupling. However, the detection and quantification of surface-immobilized small molecules such as fitranones presents a considerable analytical challenge, yet is necessary for optimization of coatings and reliable interpretation of biological responses. We have utilized the surface sensitivity and chemical specificity of time-of-flight secondary ion mass spectrometry (TOF-SIMS) to characterize each step of the grafting sequence. On account of the complexity of the data, principal component analysis (PCA) was used to interpret and compare spectra. The results demonstrate the utility of TOF-SIMS with PCA for the detection of the surface-grafted small molecules azidoaniline and a brominated furanone; imaging of the bromine ion peaks also enabled assessment of grafting uniformity. Thus, successful multilayer coating and furanone grafting was observed, and substantial and uniform coverage of furanone molecules on the surface. Even multiple grafting steps involving, in the present case, two low molecular weight compounds can readily be disentangled by PCA. The utility of TOF-SIMS analysis with PCA is particularly well illustrated in the present case by the grafting of the furanone molecules, which did not yield a singular unique peak in the positive ion mass spectra, whereas the collective spectral changes elucidated by PCA provided unambiguous verification of successful grafting of this low molecular weight compound.

Candida auris is known to survive for weeks on solid material surfaces. Its longevity contributes to medical device contamination and spread through healthcare facilities. We fabricated antifungal surface coatings by coating plastic and glass surfaces with a thin polymer layer to which the antifungal drug caspofungin was covalently conjugated. Caspofungin-susceptible and -resistant C. auris strains were inhibited on these surfaces by 98.7 and 81.1%, respectively. Cell viability studies showed that this inhibition was fungicidal. Our findings indicate that C. auris strains can be killed on contact when exposed to caspofungin that is reformulated as a covalently-bound surface layer. Lay summary Candida auris is pathogenic, multidrug resistant yeast with the ability to survive on surfaces and remain transmissible for long periods of time in healthcare settings. In this study, we have prepared an antifungal surface coating and demonstrated its ability to kill adhering C. auris cells on contact. [ABSTRACT FROM AUTHOR]

There are many reports of antimicrobial coatings bearing immobilized active agents on surfaces; however, strong analytical evidence is required to verify that the agents are indeed covalently attached to the surface. In the absence of such evidence, antimicrobial activity could result from a release of active agents. We report a detailed assessment of antifungal surface coatings prepared using covalent attachment chemistries, with the aim of establishing a set of instrumental and biological evidence required to convincingly demonstrate antimicrobial activity due to nonreleasing, surface active compounds and to exclude the alternate possibility of activity due to release. The strongest biological evidence initially supporting permanent antifungal activity was the demonstration of the ability to reuse samples in multiple, sequential pathogen challenges. However, additional supporting evidence from washing studies and instrumental analysis is also required to probe the possibility of gradual desorption of strongly physisorbed compounds versus covalently attached compounds. Potent antifungal surface coatings were prepared from approved pharmaceutical compounds from the echinocandin drug class (caspofungin, anidulafungin, and micafungin) and assessed by microbiological tests and instrumental methods. Carbonyl diimidazole linking chemistry enabled covalent attachment of caspofungin, anidulafungin, and micafungin to plasma polymer surfaces, with antifungal surface activity likely caused by molecular orientations that present the lipophilic tail toward interfacing fungal cells. This study demonstrates the instrumental and biological evidence required to convincingly ascertain activity due to nonreleasing, surface active compounds and summarize these as three criteria for assessing other reports on surface-immobilized antimicrobial compounds. [ABSTRACT FROM AUTHOR]

Improved retention of desirable chemical structures during plasma polymerization requires rational tailoring of plasma‐phase conditions. Using ethyl trimethylacetate, we studied the effects of pressure and power on the contribution of intact molecular ions to deposition and retention of ester groups. The abundance of protonated molecular ions in plasmas varies with pressure and power, but the functionality of plasma polymers, assessed by X‐ray photoelectron spectroscopy and time‐of‐flight secondary ion mass spectrometry, is not correlated. Together with high ion flux, the ion energy distribution was found to be a key parameter and needs to be tailored to enable the soft landing of ions on the surface after traversing the sheath. The compromise between the abundance of ions and their energy distribution is optimal near the transition between the α and γ plasma phases. [ABSTRACT FROM AUTHOR]

A drug-eluting coating applied onto biomedical devices and implants is an appropriate way to ensure that an inhibitory concentration of antimicrobial drugs is present at the device surface, thus preventing surface colonization and subsequent biofilm formation. In this study, a thin polymer coating was applied to materials, and it acted as a drug-delivery reservoir capable of surface delivery of the antifungal drug fluconazole to amounts up to 21 μg/cm2. The release kinetics into aqueous solution were quantified by UV spectroscopy and conformed to the Ritger–Peppas and Korsmeyer–Peppas model. Complementary microbiological assays were used to determine effectiveness against Candida albicans attachment and biofilm formation, and against the control heptylamine plasma polymer coating without drug loading, on which substantial fungal growth occurred. Fluconazole release led to marked antifungal activity in all assays, with log 1.6 reduction in CFUs/cm2. Cell viability assays and microscopy revealed that fungal cells attached to the fluconazole-loaded coating remained rounded and did not form hyphae and biofilm. Thus, in vitro screening results for fluconazole-releasing surface coatings showed efficacy in the prevention of the formation of Candida albicans biofilm. [ABSTRACT FROM AUTHOR]

Amphiphilic polymers bearing cationic moieties are an emerging alternative to traditional antibiotics given their broad-spectrum activity and low susceptibility to the development of resistance. To date, however, much remains unclear regarding their mechanism of action. Using functional assays (ATP leakage, cell viability, DNA binding) and super-high resolution structured illumination microscopy (OMX-SR) of fluorescently tagged polymers, we present evidence for a complex mechanism, involving membrane permeation as well as cellular uptake, interaction with intracellular targets and possible complexation with bacterial DNA. This manuscript details the first study to systematically and directly investigate the mechanism of action of antimicrobial polymers, using super-resolution fluorescence imaging as well as functional assays. While many in the field cite membrane permeation as the sole mechanism underlying the activity of such polymers, we present evidence for multimodal actions including high cellular uptake and interaction with intracellular targets. It is also the first report to show competitive binding of antimicrobial polymers with bacterial DNA in a dose-dependent manner. Image, graphical abstract [ABSTRACT FROM AUTHOR]