Coatings For Biomedical Devices Research Articles

Mussel-Inspired Polymer-Based Coating Technology for Antifouling and Antibacterial Properties.

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.

Atmospheric Pressure Plasma Polymerization of Carvone: A Promising Approach for Antimicrobial Coatings

Medical devices are often vulnerable to colonization by nosocomial pathogens (bacteria), leading to infections. Traditional sterilization methods may not always be effective, and as a result, alternative options are being explored to prevent microbial contamination. Recently, scientists are emphasizing using plant-derived essential oils that possess inherent antibacterial properties to produce antimicrobial coatings using plasma polymerization technology carried out at atmospheric pressure (AP). This approach shows promise compared to other coating strategies that need several processing steps, including a high-vacuum system, and are laborious, such as the immobilization of antimicrobial materials on precoated layers in the low-pressure plasma polymerization approach. The present study demonstrates the potential of AP plasma polymerization for producing thin films with excellent antibacterial properties and surface characteristics. The resulting coatings are stable, smooth, and have high wettability, making them ideal for repelling bacteria. The calculated zeta potential and deposition rate for the films are also favorable. These AP plasma-polymerized thin films created from carvone show a reduction rate of more than 90% for Escherichia coli and Staphylococcus aureus bacteria. Our computational docking studies also reveal strong binding interactions between the original carvone monomer and both bacteria. The study suggests that these AP plasma-produced coatings have great potential as antibacterial coatings for biomedical devices.

Microgel reinforced zwitterionic hydrogel coating for blood-contacting biomedical devices

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.

Novelty in the development of biodegradable polymer coatings for biomedical devices: paclitaxel grafting on PDMMLA derivatives

ABSTRACT Biocompatible and biodegradable polymers are widely used in the medical field. In some cases, the biopolymer is accompanied by an active drug, which is delivered locally in a controlled manner in order to improve the healing conditions. Poly([R,S]-3,3-dimethylmalic acid) (PDMMLA) is a synthetic amphiphilic biodegradable polymer, which unlike PLA, can be chemically modified to adapt hydrophilic/hydrophobic balance, degradation kinetics, and physicochemical and biological properties. It may contain a lateral alkyl group or a functional group for coupling bioactive molecules to release during its degradation. In this work, we realized the chemical grafting of paclitaxel (PTX), a microtubule stabilizing anti-cancer agent on PDMMLA derivatives bio-polyesters following a Steglich esterification protocol. 1D and 2D NMR analyses validated the reaction with 10% (using 0.1 equivalent) of PTX on the copolymer PDMMLAH40-co-Hex60 (PDMMLA 40/60) and a maximal PTX grafting rate of 55% on the homopolymer PDMMLAH (PDMMLA 100/0). In vitro adhesion and cytotoxicity assays were carried out on HUVEC cells with PDMMLA 40/60, PDMMLA-PTX 30/10/60 and PLA.

Developmental exposure to silver nanoparticles leads to long term gut dysbiosis and neurobehavioral alterations

Due to their antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such AgNPs may lead to gut dysbiosis and long-term health consequences in exposed offspring. AgNPs can cross the placenta and blood–brain-barrier to translocate in the brain of offspring. The underlying hypothesis tested in the current study was that developmental exposure of male and female mice to AgNPs disrupts the microbiome–gut–brain axis. To examine for such effects, C57BL6 female mice were exposed orally to AgNPs at a dose of 3 mg/kg BW or vehicle control 2 weeks prior to breeding and throughout gestation. Male and female offspring were tested in various mazes that measure different behavioral domains, and the gut microbial profiles were surveyed from 30 through 120 days of age. Our study results suggest that developmental exposure results in increased likelihood of engaging in repetitive behaviors and reductions in resident microglial cells. Echo-MRI results indicate increased body fat in offspring exposed to AgNPs exhibit. Coprobacillus spp., Mucispirillum spp., and Bifidobacterium spp. were reduced, while Prevotella spp., Bacillus spp., Planococcaceae, Staphylococcus spp., Enterococcus spp., and Ruminococcus spp. were increased in those developmentally exposed to NPs. These bacterial changes were linked to behavioral and metabolic alterations. In conclusion, developmental exposure of AgNPs results in long term gut dysbiosis, body fat increase and neurobehavioral alterations in offspring.

Analytical strategy for studying the formation and stability of multilayered films containing gold nanoparticles.

The design of layer-by-layer (LbL) polyelectrolyte films including nanoparticles is a growing field of innovation in a wide range of biomedical applications. Gold nanoparticles (AuNPs) are very attractive for further biomolecule coupling to induce a pharmacological effect. Nanostructured LbL films coupled with such metallic species show properties that depend on the conditions of construction, i.e. the polymer nature and dissolution buffer. Tripartite LbL films (polycation, AuNP, and polyanion) were evaluated using two different polycationic polymers (poly(allylamine hydrochloride) (PAH), poly(ethylene imine) (PEI)) and various medium conditions (salts, i.e. phosphate, Tris or Tris-NaCl buffers, and concentration). AuNP incorporation and film stability were analysed by visible spectrophotometry, capillary zone electrophoresis, a quartz crystal microbalance, and high-performance liquid chromatography. The ideal compromise between AuNP loading and film stability was obtained using PAH prepared in Tris-NaCl buffer (0.01-0.15M). This condition allowed the formation of a LbL film that was more stable than the film with PEI and provided an AuNP quantity that was 4.8 times greater than that of the PAH-PBS-built film. In conclusion, this work presents an analytical strategy for the characterization of nanostructured multilayer films and optimization of LbL films enriched with AuNPs to design biomedical device coatings.

Surface Immobilization Chemistry of a Laminin-Derived Peptide Affects Keratinocyte Activity.

Many chemical routes have been proposed to immobilize peptides on biomedical device surfaces, and in particular, on dental implants to prevent peri-implantitis. While a number of factors affect peptide immobilization quality, an easily controllable factor is the chemistry used to immobilize peptides. These factors affect peptide chemoselectivity, orientation, etc., and ultimately control biological activity. Using many different physical and chemical routes for peptide coatings, previous research has intensely focused on immobilizing antimicrobial elements on dental implants to reduce infection rates. Alternatively, our strategy here is different and focused on promoting formation of a long-lasting biological seal between the soft tissue and the implant surface through transmembrane, cell adhesion structures called hemidesmosomes. For that purpose, we used a laminin-derived call adhesion peptide. However, the effect of different immobilization chemistries on cell adhesion peptide activity is vastly unexplored but likely critical. Here, we compared the physiochemical properties and biological responses of a hemidesmosome promoting peptide immobilized using silanization and copper-free click chemistry as a model system for cell adhesion peptides. Successful immobilization was confirmed with water contact angle and X-ray photoelectron spectroscopy. Peptide coatings were retained through 73 days of incubation in artificial saliva. Interestingly, the non-chemoselective immobilization route, silanization, resulted in significantly higher proliferation and hemidesmosome formation in oral keratinocytes compared to chemoselective click chemistry. Our results highlight that the most effective immobilization chemistry for optimal peptide activity is dependent on the specific system (substrate/peptide/cell/biological activity) under study. Overall, a better understanding of the effects immobilization chemistries have on cell adhesion peptide activity may lead to more efficacious coatings for biomedical devices.

Surface modification approaches for prevention of implant associated infections

In this highlight, we summarize the surface modification approaches for development of infection-resistant coatings for biomedical devices and implants. We discuss the relevant key and highly cited research that have been published over the last five years which report the generation of infection-resistant coatings. An important strategy utilized to prevent bacterial adhesion and biofilm formation on device/implant surface is anti-adhesive protein repellant polymeric coatings based on polymer brushes or highly hydrated hydrogel networks. Further, the attachment of antimicrobial agents that can efficiently kill bacteria on the surface while also prevent bacterial adhesion on the surface is also investigated. Other approaches include the incorporation of antimicrobial agents to the surface coating resulting in a depot of bactericides which can be released on-demand or with time to prevent bacterial colonization on the surface that kill the adhered bacteria on the surface to make surface infection resistant.

Mussel-Inspired, Surface-Attachable Initiator for Grafting of Antimicrobial and Antifouling Hydrogels.

In this work, a novel biomimetic surface-attachable initiator is successfully synthesized by the conjugation of 3,4-dihydroxyphenylacetic acid and thermal 2,2'-azobis(2-methylpropionamide) dihydrochloride (V-50). The synthesized initiator (DOPV) can adhere to various material surfaces in a mussel-inspired way and initiate the surface grafting polymerization. Hydrogel coatings are facilely prepared by the thermal-initiated radical copolymerization of antimicrobial polyhexamethylene guanidine and antifouling polyethylene glycol oligomers. The developed hydrogel coatings not only show antimicrobial activity toward gram-negative and gram-positive bacteria but also demonstrate protein resistance, antibiofilm efficacy, hemocompatibility, and low cytotoxicity in vitro. Most importantly, the hydrogel coatings reveal excellent antimicrobial efficacy with a log reduction above 5 in a rodent subcutaneous infection model. These results demonstrate the potential fabrication of bio-functional coatings for biomedical devices or implants through an inexpensive, facile, and environmentally friendly mussel-inspired technique.

Co-Deposition and Characterization of Hydroxyapatite-Chitosan and Hydroxyapatite-Polyvinylacetate Coatings on 304 SS for Biomedical Devices

During the last decades, biomaterials have been deeply studied to perform and improve coatings for biomedical devices. Metallic materials, especially in the orthopedic field, represent the most common material used for different type of devices thanks to their good mechanical properties. Nevertheless, low/medium resistance to corrosion and low osteointegration ability characterizes these materials. To overcome these problems, the use of biocoatings on metals substrate is largely diffused. In fact, biocoatings have a key role to confer biocompatibility properties, to inhibit corrosion and thus improve the lifetime of implanted devices. In this work, the attention was focused on Hydroxyapatite-Chitosan (HA/CS) and Hydroxyapatite-Polyvinylacetate (HA/PVAc) composites, that have been studied as biocoatings for 304 SS based devices. Hydroxyapatite was selected for its osteoconductivity thanks to its chemical structure similar to bones. Furthermore, Chitosan and Polyvinylacetate are largely used yet in medical field (e.g. antibacterial agent or drug deliver) and in this work were used to create a synergic interaction with hydroxyapatite to increase the strength and bioactivity of coating. Biocotings were obtained by galvanic deposition process that does not require an external power supply. It is a spontaneous electrochemical deposition in which materials with different standard electrochemical potential were short-circuited and immersed in an electrolytic solution. Electrons supply for the cathodic reaction in the noblest material comes from oxidation of the less noble material. SEM, EDS, XRD and RAMAN were performed for chemical-physics characterization of biocoatings. Polarization and impedance measurements have been carried out to evaluate corrosion behavior. Besides, in-vitro cytotoxicity assays have been done for the biological features.

Silver Nanoparticles: Synthesis and Application for Nanomedicine.

Over the past few decades, metal nanoparticles less than 100 nm in diameter have made a substantial impact across diverse biomedical applications, such as diagnostic and medical devices, for personalized healthcare practice. In particular, silver nanoparticles (AgNPs) have great potential in a broad range of applications as antimicrobial agents, biomedical device coatings, drug-delivery carriers, imaging probes, and diagnostic and optoelectronic platforms, since they have discrete physical and optical properties and biochemical functionality tailored by diverse size- and shape-controlled AgNPs. In this review, we aimed to present major routes of synthesis of AgNPs, including physical, chemical, and biological synthesis processes, along with discrete physiochemical characteristics of AgNPs. We also discuss the underlying intricate molecular mechanisms behind their plasmonic properties on mono/bimetallic structures, potential cellular/microbial cytotoxicity, and optoelectronic property. Lastly, we conclude this review with a summary of current applications of AgNPs in nanoscience and nanomedicine and discuss their future perspectives in these areas.

Large-area alginate/PEO-PPO-PEO hydrogels with thermoreversible rheology at physiological temperatures

Alginate hydrogels have shown great promise for applications in wound dressings, drug delivery, and tissue engineering. This report details the fabrication and rheological properties of a multicomponent hydrogel consisting of alginate and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, and the achievement of thick, castable gels with tunable, thermoreversible behavior at physiological temperatures. PEO-PPO-PEO triblock copolymers can form temperature-sensitive hydrogels that exist as liquids at low temperatures and soft solids at high temperatures. In this work, we have employed PEO-PPO-PEO triblock copolymers to impart thermoresponsive properties to alginate hydrogels in the form of a multicomponent hydrogel. These systems can transition between a weak gel and a stiff gel, with a corresponding increase in the viscoelastic moduli of approximately two orders of magnitude as temperature is increased. The temperatures corresponding to the upper and lower boundaries of the stiff gel region, as well as the storage modulus at physiological temperatures (e.g., 36–40 °C), can be controlled through the PEO-PPO-PEO concentration. Optically clear gels that are homogeneous on the microscale can be fabricated in a scalable manner to create flat, large-area thick films, making these systems favorable for applications in wound healing, soft tissue repair, and biomedical device coatings.

Investigation of Antibacterial 1,8-Cineole-Derived Thin Films Formed via Plasma-Enhanced Chemical Vapor Deposition.

The need for low-fouling coatings for biomedical devices has prompted considerable interest in antibacterial compounds from natural and sustainable sources, such as essential oils. Herein, a tea tree oil-based precursor, 1,8-cineole, is used to fabricate antimicrobial films (denoted ppCin) by plasma-enhanced chemical vapor deposition. Film properties were comprehensively characterized using a variety of surface and bulk analytical tools, and the plasma gas phase is assessed using optical emission spectroscopy, which can be correlated to ppCin film properties. Notably, film wettability increases linearly with plasma pressure, yielding water contact angles ranging from ∼50° to ∼90°. X-ray photoelectron spectroscopy reveals less oxygen is incorporated at higher pressures, likely arising from the lower density of OH(g) species. Further, we utilized H2O(v) plasma surface modification of the ppCin films to improve wettability and find this results in a substantial increase in surface oxygen content. To elucidate the role of film wettability and antibacterial properties, both as-deposited and H2O(v) plasma-modified films were exposed to Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus using glass slides and hydrocarbon films deposited from 1,7-octadiene as positive controls. Overall, bacteria attach to a similar extent on all films, including controls, yet only essential oil-based films significantly prevent biofilm formation (4-7% coverage compared to ∼40% for controls).

Caspofungin on ARGET-ATRP grafted PHEMA polymers: Enhancement and selectivity of prevention of attachment of Candida albicans.

There is a need for coatings for biomedical devices and implants that can prevent the attachment of fungal pathogens while allowing human cells and tissue to appose without cytotoxicity. Here, the authors study whether a poly(2-hydroxyethylmethacrylate) (PHEMA) coating can suppress attachment and biofilm formation by Candida albicans and whether caspofungin terminally attached to surface-tethered polymeric linkers can provide additional benefits. The multistep coating scheme first involved the plasma polymerization of ethanol, followed by the attachment of α-bromoisobutyryl bromide (BiBB) onto surface hydroxyl groups of the plasma polymer layer. Polymer chains were grafted using surface initiated activators regenerated by electron transfer atom transfer radical polymerization with 2-hydroxyethylmethacrylate, yielding PHEMA layers with a dry thickness of up to 89 nm in 2 h. Hydroxyl groups of PHEMA were oxidized to aldehydes using the Albright-Goldman reaction, and caspofungin was covalently immobilized onto them using reductive amination. While the PHEMA layer by itself reduced the growth of C. albicans biofilms by log 1.4, the addition of caspofungin resulted in a marked further reduction by >4 log units to below the threshold of the test. The authors have confirmed that the predominant mechanism of action is caused by antifungal drug molecules that are covalently attached to the surface, rather than out-diffusing from the coating. The authors confirm the selectivity of surface-attached caspofungin in eliminating fungal, not mammalian cells by showing no measurable toxicity toward the myeloid leukaemia suspension cell line KG-1a.

Configurable microfluidic platform for investigating therapeutic delivery from biomedical device coatings.

Advanced biomedical device coatings have shown significant promise in delivery of therapeutics (e.g., small-molecule drugs, proteins) for a wide range of medical interventions ranging from targeted cancer therapy to management of atherosclerosis. In order to accelerate the development of such coatings, there is a need for tools to investigate the loading capacity and release kinetics with high temporal resolution and in a variety of physiological conditions. To address this need, we report a microfluidic platform, where the coating on a substrate can be mounted onto the microchannel and the device can be configured in two physiologically-relevant modes: (i) flow-mode allows for monitoring the release from the coating in contact with a liquid flowing at a specific rate, modeling the case of a drug-eluting stent. (ii) Static-mode, where the channel is filled with a stationary gel, mimics the case of drug-eluting brain implant. We demonstrate the utility of the platform with a fluorescein-loaded nanoporous gold coating and monitor in real-time the release kinetics both under deionized water infusion and an agarose gel-filled channel via fluorescence microscopy coupled to a LabVIEW-based interface.

Antibacterial polyurethane materials with silver and copper nanoparticles

New biologically active polyurethanes with silver and copper nanoparticles in their composition were prepared by saturation of liquid polyether (the initial component for polyurethane synthesis) with nanoparticles (Ag, Cu), followed by synthesis of polyurethane. The results of these studies allow consideration of these materials as medical suppliers with antibacterial properties. The main problem of their creation is uniform distribution of the metal nanoparticles inside the polymer matrix without changing the physico-chemical properties of the latter. Obtaining of metal nanoparticles’ colloid in a liquid polyoxytetramethylene glycol, MM 1000 was carried out by electron beam evaporation technology and vacuum deposition. This method allowed creating, on the basis of obtained colloids, the metal-containing polyurethane materials with targeted properties and structure that are determined by diisocyanates and chain extenders nature. Biological study has shown that polyurethanes containing Cu and Ag nanoparticles possess bactericidal/bacteriostatic effect against bacteria, fungi and yeast-like fungi. Polymer samples did not exhibit toxicity to the tissue culture cells and there were no biodegradation products observed in the culture medium. Resulting biologically active metal-containing polyurethane materials can be processed into products for medical purposes (implants, drug delivery systems, antimicrobial coatings for biomedical devices and antimicrobial packaging) by standard methods of polyurethane processing, since the presence of metal nanoparticles in their composition does not affect the physical properties of the polymer.

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation.

As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.

Effect of Winemaking on the Composition of Red Wine as a Source of Polyphenols for Anti-Infective Biomaterials.

Biomaterials releasing bactericides have currently become tools for thwarting medical device-associated infections. The ideal anti-infective biomaterial must counteract infection while safeguarding eukaryotic cell integrity. Red wine is a widely consumed beverage to which many biological properties are ascribed, including protective effects against oral infections and related bone (osteoarthritis, osteomyelitis, periprosthetic joint infections) and cardiovascular diseases. In this study, fifteen red wine samples derived from grapes native to the Oltrepò Pavese region (Italy), obtained from the winemaking processes of “Bonarda dell’Oltrepò Pavese” red wine, were analyzed alongside three samples obtained from marc pressing. Total polyphenol and monomeric anthocyanin contents were determined and metabolite profiling was conducted by means of a chromatographic analysis. Antibacterial activity of wine samples was evaluated against Streptococcus mutans, responsible for dental caries, Streptococcus salivarius, and Streptococcus pyogenes, two oral bacterial pathogens. Results highlighted the winemaking stages in which samples exhibit the highest content of polyphenols and the greatest antibacterial activity. Considering the global need for new weapons against bacterial infections and alternatives to conventional antibiotics, as well as the favorable bioactivities of polyphenols, results point to red wine as a source of antibacterial substances for developing new anti-infective biomaterials and coatings for biomedical devices.

Advanced biomedical device coatings inspired by prebiotic chemistry

Advanced biomedical device coatings inspired by prebiotic chemistry

Characteristics, interactions and coating adherence of heterogeneous polymer/drug coatings for biomedical devices

With this rise in surgical procedures it is important to focus on the mobility and safety of the patient and reduce the infections that are associated with hip replacements. We examine the mechanical properties of gentamicin sulphate as a model antimicrobial layer for titanium-alloy based prosthetic hips to help prevent methicillin-resistant Staphylococcus aureus infection after surgery. A top layer of poly(lactic-co-glycolic acid) is added to maintain the properties of the gentamicin sulphate as well as providing a drug delivery system. Through the use of nanoindentation and micro-scratch techniques it is possible to determine the mechanical and adhesive properties of this system. Nanoindentation determined the modulus values for the poly(lactic-co-glycolic acid) and gentamicin sulphate materials to be 8.9 and 5.2GPa, respectively. Micro-scratch established that the gentamicin sulphate layer is strongly adhered to the Ti alloy and forces of 30N show no cohesive or adhesive failure. It was determined that the poly(lactic-co-glycolic acid) is ductile in nature and delaminates from the gentamicin sulphate layer of at 0.5N.