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Antimicrobial/Antifouling Polycarbonate Coatings: Role of Block Copolymer Architecture
Abstract
The high prevalence of catheter-associated infections accounts for more than 3 billion dollars annually in hospitals, and antimicrobial polymer coatings on catheter surface may serve as an attractive weapon to mitigate infections. Triblock polycarbonate polymers consisting of three critical components including antifouling poly(ethylene glycol) (PEG), antimicrobial cationic polycarbonate, and a tethering or adhesive functional block were synthesized. In this study, the block topology or placement of the distinctive blocks was varied and their efficacy as antimicrobial and antifouling agents investigated on coated surfaces. The individual blocks were designed to have comparable lengths that were subsequently grafted onto a prefunctionalized catheter surface through covalent bonding under mild conditions. The anchoring/adhesive functional moiety based on a maleimide functional carbonate was positioned at either the center or end of the polymer block and subsequently tethered to the surface via Michael addition chemistry. The placement of the adhesive block was investigated in terms of its effect on antimicrobial and antifouling properties. The surface coated with the polymer containing the center-positioned tethering block (2.4k-V) was unable to prevent bacteria fouling, even though demonstrated higher bacteria killing efficacy in solution as compared to the surface coated with the polymer containing the end-positioned tethering block (2.4k-S). In contrast, the 2.4k-S coating resisted fouling of both Gram-positive S. aureus and Gram-negative E. coli effectively under conditions that simulate the device lifetime (1 week). Moreover, the coating prevented protein fouling and platelet adhesion without inducing significant hemolysis. Consequently, this antibacterial and antifouling polymer coating is an interesting candidate to prevent catheter-associated bloodstream infections.
... Antiadhesive PEG can further be used, along with a cationic PC combined either with tethering or with an adhesive functional block, to synthesize V-and S-shaped triblock copolymers by placing the tethering block centrally or at the end, respectively [172]. While the surfaces coated with V-shaped polymer exhibited antibacterial properties but without being able to prevent microbial adhesion, the surfaces coated with S-shaped polymer exhibited strong antibacterial and antiadhesive attributes [172]. ...
... Antiadhesive PEG can further be used, along with a cationic PC combined either with tethering or with an adhesive functional block, to synthesize V-and S-shaped triblock copolymers by placing the tethering block centrally or at the end, respectively [172]. While the surfaces coated with V-shaped polymer exhibited antibacterial properties but without being able to prevent microbial adhesion, the surfaces coated with S-shaped polymer exhibited strong antibacterial and antiadhesive attributes [172]. In comparison, linear PEGb-PC diblock copolymers were also reported to exhibit both antiadhesive and antimicrobial properties when grafted onto PDA-covered silicone rubber surfaces [173]. ...
Pathogenic microbes are the main cause of various undesired infections in living organisms, including humans. Most of these infections are favored in hospital environments where humans are being treated with antibiotics and where some microbes succeed in developing resistance to such drugs. As a consequence, our society is currently researching for alternative, yet more efficient antimicrobial solutions. Certain natural and synthetic polymers are versatile materials that have already proved themselves to be highly suitable for the development of the next-generation of antimicrobial systems that can efficiently prevent and kill microbes in various environments. Here, we discuss the latest developments of polymeric structures, exhibiting (reinforced) antimicrobial attributes that can be assembled on surfaces and coatings either from synthetic polymers displaying antiadhesive and/or antimicrobial properties or from blends and nanocomposites based on such polymers.
... The stable and long-term antibacterial effects of different films towards E. coli and S. aureus were also investigated through the optical density method [43]. Briefly, the pre-prepared bacterial suspension was diluted to 3 × 10 5 CFU/mL and then, the diluted bacterial suspension Scanning electron microscope (SEM, Hitachi, S-4800, Japan) was applied to detect the attachment of two kinds of bacteria on the prepared film surfaces and the biofilm formation [44]. The samples were made as the same procedure of optical density method stated above. ...
... Bacterial adhesion, especially biofilm formation, has a fatal weakening effect on the properties of film materials. Biofilm consists of live or dead bacteria, organic debris, the secreted extracellular matrix as well as other impurities, which are extremely hard to remove [42,44]. Therefore, the antibiofouling and anti-biofilm formation properties are of great significance to the application of the antibacterial films. ...
Due to the extraordinary photocatalytic effect, TiO2 nanoparticles (TiO2 NPs) have been widely applied in antibacterial fields. However, the agglomeration problem and dependence on light of TiO2 NPs seriously limit their antibacterial activity and practical applications. This study proposed an ingenious, facile and effective strategy for the preparation of polyacrylate/TiO2 nanocomposite antibacterial films by emulsion polymerization. In this work, a quaternary ammonium cationic ligand Vinylbenzyldimethyldodecylammonium chloride (VDAC) was successfully synthesized, which acted as a trinity of cationic ligand, organic antibacterial agent and polymerizable emulsifier to improve the dispersion of TiO2 NPs by electrostatic interaction and play the synergistic antibacterial effect with TiO2 NPs. The results demonstrated that TiO2 NPs were truly uniformly dispersed in the matrix and the particles sizes were reduced to around 5 nm. Moreover, the systematic investigations of antibacterial performance indicated that the prepared nanocomposite films displayed excellent antibacterial and antibiofouling abilities through the synergistic antibacterial effect of TiO2 NPs and VDAC. The films could maintain close to 100 % antibacterial rate and completely inhibit bacterial adhesion and biofilm formation in 7 days, exhibiting long-term and stable antibacterial performance. The nanocomposite films in this work exhibit a great potential to be applied to antibacterial coatings and other fields requiring high antibacterial properties.
... Zhou and collaborators [30] revised the different strategies to fabricate brushes on a wide variety of surfaces, either from physical adsorption or by chemical coupling reactions, grafting copolymers by surface initiated radical polymerization (SIRP). In different research, Yang et al. [31] focused on the study of antibacterial properties vs. the blockcopolymer structure. The copolymers consisted of three blocks, an antifouling PEG, antibacterial cationic polycarbonate, and maleimide-functionalized polycarbonate (so that the blocks could be anchored on the surface of a silicone rubber, like those used for a catheter tube). ...
... However, the visualization of surfaces with other microscopy techniques, such as SEM, can provide important information on bacterial growth and biofilm formation. For example, in a research work by Yang and colleagues [31], SEM micrographs on the surfaces of different samples after one day culture with E. Coli strain were done ( Figure 13). SEM micrographs showed that a biofilm was formed on pristine, thiol-functionalized and 2.4k-V surfaces, whereas just isolated bacteria were observed in the 2.4 k-S surface. ...
Infections caused by bacteria are one of the main causes of mortality in hospitals all over the world. Bacteria can grow on many different surfaces and when this occurs, and bacteria colonize a surface, biofilms are formed. In this context, one of the main concerns is biofilm formation on medical devices such as urinary catheters, cardiac valves, pacemakers or prothesis. The development of bacteria also occurs on materials used for food packaging, wearable electronics or the textile industry. In all these applications polymeric materials are usually present. Research and development of polymer-based antibacterial materials is crucial to avoid the proliferation of bacteria. In this paper, we present a review about polymeric materials with antibacterial materials. The main strategies to produce materials with antibacterial properties are presented, for instance, the incorporation of inorganic particles, micro or nanostructuration of the surfaces and antifouling strategies are considered. The antibacterial mechanism exerted in each case is discussed. Methods of materials preparation are examined, presenting the main advantages or disadvantages of each one based on their potential uses. Finally, a review of the main characterization techniques and methods used to study polymer based antibacterial materials is carried out, including the use of single force cell spectroscopy, contact angle measurements and surface roughness to evaluate the role of the physicochemical properties and the micro or nanostructure in antibacterial behavior of the materials.
... biofilm formation or eliminate already-constructed biofilms is well established [20][21][22]. Efficient antimicrobial coatings can prevent bacteria adhesion or kill the bacteria before or after contact with the surface, although many strategies include both mechanisms [23][24][25][26]. ...
... To overcome this problem, an urgent need for the development of coatings that are able to prevent prevent biofilm formation or eliminate already-constructed biofilms is well established [20][21][22]. Efficient antimicrobial coatings can prevent bacteria adhesion or kill the bacteria before or after contact with the surface, although many strategies include both mechanisms [23][24][25][26]. ...
Biocidal coatings that are based on quaternized ammonium copolymers were developed after blending and crosslinking and studied as a function of the ratio of reactive groups and the type of biocidal groups, after curing at room temperature or 120 °C. For this purpose, two series of copolymers with complementary reactive groups, poly(4-vinylbenzyl chloride-co-acrylic acid), P(VBC-co-AAx), and poly(sodium 4-styrenesulfonate-co-glycidyl methacrylate), P(SSNa-co-GMAx), were synthesized via free radical copolymerization and further modified resulting in covalently bound (4-vinylbenzyl dimethylhexadecylammonium chloride, VBCHAM) and electrostatically attached (hexadecyltrimethylammonium 4-styrene sulfonate, SSAmC16) units. The crosslinking reaction between the carboxylic group of acrylic acid (AA) and the epoxide group of glycidyl methacrylate (GMA) of these copolymers led to the stabilization of the coatings through reactive blending. The so developed coatings were cured at room temperature and 120 °C, and then immersed in ultra-pure water and aqueous NaCl solutions at various concentrations for a time period up to three months. Visual inspection of the integrity of the materials coated onto glass slides, gravimetry, scanning electron microscopy (SEM) characterization, as well as the determination of total organic carbon (TOC) and total nitrogen (TN) of the solutions, were used to investigate the parameters affecting the release of the materials from the coatings based on these systems. The results revealed that curing temperature, complementary reactive groups' content, and type of antimicrobial species control the release levels and the nature of releasable species of these environmentally-friendly antimicrobial coatings.
... However, most of these coatings can only prevent bacterial adhesion to a certain extent but fail to inhibit the growth of pathogenic bacteria. The coating surface may become contaminated, and bacteria can continue to live and colonize on them to compromise its anti-adhesion properties [138]. In the complex environment containing multiple biomolecules in the human body, most of these coatings have no long-term stability. ...
With the aging of population and the rapid improvement of public health and medical level in recent years, people have had an increasing demand for orthopedic implants. However, premature implant failure and postoperative complications frequently occur due to implant-related infections, which not only increase the social and economic burden, but also greatly affect the patient's quality of life, finally restraining the clinical use of orthopedic implants. Antibacterial coatings, as an effective strategy to solve the above problems, have been extensively studied and motivated the development of novel strategies to optimize the implant. In this paper, a variety of antibacterial coatings recently developed for orthopedic implants were briefly reviewed, with the focus on the synergistic multi-mechanism antibacterial coatings, multi-functional antibacterial coatings, and smart antibacterial coatings that are more potential for clinical use, thereby providing theoretical references for further fabrication of novel and high-performance coatings satisfying the complex clinical needs.
... According to their bactericidal characteristics, anti-adhesive bactericidal coatings can be divided into anti-adhesive contact bactericidal coatings and anti-adhesive release bactericidal coatings. Voo et al. [140] synthesized a tri-block polycarbonate polymer anti-adhesive contact bactericidal coating using PEG, antimicrobial cationic polycarbonate, and maleimide-functionalized polycarbonate, and achieved a 99.4% kill rate against Staphylococcus aureus. Paris et al. [141,142] constructed a contact bactericidal coating with an excellent killing effect on drug-resistant bacteria by pre-modifying hyaluronic acid on the surface of the material and immobilizing Streptococcus lactis peptides coupled with hyaluronic acid on the surface, which also avoided the accumulation of dead cells and maintained long-lasting antimicrobial properties. ...
In recent years, biomedical materials have been used in the response to the emergence of medical infections that pose a serious threat to the health and life of patients. The construction of superhydrophobic coatings and antimicrobial coatings is among the most effective strategies to address this type of medical derived infection. Firstly, this paper reviews the preparation methods of superhydrophobic surface coatings and their applications; summarizes the advantages and disadvantages of superhydrophobic surface preparation schemes based on the template method, spraying methods, etching methods, and their respective improvement measures; and focuses on the applications of superhydrophobic surfaces in self-cleaning and antibacterial coatings. Then, the action mechanisms of contact antibacterial coatings, anti-adhesion bacteriostatic coatings, anti-adhesion bactericidal coatings, and intelligent antibacterial coatings are introduced, and their respective characteristics, advantages, and disadvantages are summarized. The application potential of antimicrobial coatings in the field of biomedical materials is highlighted. Finally, the applications of superhydrophobic and antimicrobial coatings in medical devices are discussed in detail, the reasons for their current difficulties in commercial application are analyzed, and the future directions of superhydrophobic coatings and antimicrobial coatings are considered.
... Based on reported methods, 39,40 propidium iodide and SYTO 9 (live/dead BacLight viability kit, Life Technology, Carlsbad, CA, USA) were used to label bacterial cells on as-prepared hydrogels. The bacterial suspension was obtained by mixing 15 mL of tryptic soy broth and 50 μL of log-phase cultures of E. ...
Compared with single-network hydrogels, double-network hydrogels offer higher mechanical strength and toughness. Integrating useful functions into double-network hydrogels can expand the portfolios of the hydrogels. We report the preparation of double-network metallopolymer hydrogels with remarkable hydration, antifouling, and antimicrobial properties. These cationic hydrogels are composed of a first network of cationic cobaltocenium polyelectrolytes and a second network of polyacrylamide, all prepared via radical polymerization. Antibiotics were further installed into the hydrogels via ion-complexation with metal cations. These hydrogels exhibited significantly enhanced hydration, compared with polyacrylamide-based hydrogels, while featuring robust mechanical strength. Cationic metallopolymer hydrogels exhibited strong antifouling against oppositely charged proteins. These antibiotic-loaded hydrogels demonstrated a synergistic effect on the inhibition of bacterial growth and antifouling of bacteria, as a result of the unique ion complexation of cobaltocenium cations.
... For example, lotus leaf (Nelumbonucifera) is a relatively pyramidal, rough pyramid buildings made of 3D involuntary wax crystals, which allow water after sedimentation to be far from the surface and according to self-cleaning. Bioinspired technologies beyond Lotus-effect gave an upward momentum according to major research within a selfcleaning coating, specifying the amount of self-cleaning exterior paints [3]. ...
... It is known that biofilm formation can be prevented via chemical or physical modifications. Chemical approaches incorporate biocidal materials, such as nanoparticles [28][29][30] and polymers [31,32], to resist microbial colonisation. Physical methods on the other hand alter surface topographical parameters, including aspect ratio [33], roughness [34,35] and geometry [36], to induce spatial cues that combat biofilm formation. ...
The ability to control the interactions between functional biomaterials and biological systems is of great importance for tissue engineering and regenerative medicine. However, the underlying mechanisms defining the interplay between biomaterial properties and the human body are complex. Therefore, a key challenge is to design biomaterials that mimic the in vivo microenvironment. Over millions of years, nature has produced a wide variety of biological materials optimised for distinct functions, ranging from the extracellular matrix (ECM) for structural and biochemical support of cells to the holy lotus with special wettability for self-cleaning effects. Many of these systems found in biology possess unique surface properties recognised to regulate cell behaviour. Integration of such natural surface properties in biomaterials can bring about novel cell responses in vitro and provide greater insights into the processes occurring at the cell-biomaterial interface. Using natural surfaces as templates for bioinspired design can stimulate progress in the field of regenerative medicine, tissue engineering and biomaterials science. This literature review aims to combine the state-of-the-art knowledge in natural and nature-inspired surfaces, with an emphasis on material properties known to affect cell behaviour.
... The bacterial attachment and biofilm formation by S. aureus and E. coli on the surfaces were observed by FE-SEM. 54 Fresh bacteria at the logarithmic stage of growth were collected and resuspended (to OD 600 = 0.01) in MHB. The uncoated, poly (Ppep)-, and poly(Ppep/Psar)-coated PDMS films (1 × 1 cm 2 ) were individually immersed in 2 mL of the bacterial suspension and incubated at 37°C for 7 days to allow biofilm growth. ...
Medical catheters are prone to fouling by protein adsorption and platelet adhesion/activation due to their hydrophobic surface, resulting in bacterial adhesion/biofilm formation, associated infection and thrombosis. Hence, an ultralow-fouling and exceptional infection-resistant coating on devices is urgently needed. Herein, we synthesized mussel-inspired cationic polypeptide (cPep) and mixed-charge polypeptide (mPep) via N-carboxyanhydride ring opening polymerization (NCA-ROP) method. In the view of the chemical structure, in addition to the catechol group of levodopa, the cation-ic group of L-lysine (K) and the hydrophobic group of L-phenylalanine (F), the mPep, comparing with cPep, contains the anionic group of L-glutamic acid (E) since the negatively charge amino acid sequence is newly introduced, so as to guarantee its bactericidal ability, low toxicity and surface self-deposition. Both cPep and mPep coatings are conveniently obtained by dopamine-assisted co-deposition technique. Compared with the cPep coating, the mPep coating has a similar antibacterial activity level (> 99%) against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa). Meanwhile, it is demonstrated that the mPep coating has most effective antibiofilm activity (> 3 days) and protein/platelet-resistant ability in vitro, as well as improving hemocompatibility. Furthermore, the mPep-coated silicone catheter induces no inflammatory response and significantly lowers bacterial cell number with 6-log reduction in a mouse model of infection. Consequently, the rationally designed mPep with simple coating technique has great potential in combating against medical catheter-related clinical infections.
... In order to overcome these issues, various types of polymeric (i.e. polycaprolacton (PCL) [9], chitosan [10] and polydimethylsiloxane (PDMS) [11]), ceramic (i.e. hydroxyapatite [3]) and nanocomposite (i.e. ...
The purpose of this paper was to develop the hydrophobic nanocomposite coatings of polydimethylsiloxane (PDMS)-SiO2-CuO to improve biocompatibility, corrosion resistance and antibacterial property of 316 L stainless. In this research, after synthesize of CuO and SiO2 nanopowders using wet-chemical approaches, PDMS-SiO2-CuO coatings consisting of various amounts of CuO nanoparticles were developed using dip-coating process. The nanocomposite coatings were characterized with regard to the structural and physical properties, corrosion resistance, antibacterial activity and cellular interactive responses. The results showed that incorporation of CuO nanoparticles <2 wt% improved the corrosion resistance of 316 L stainless steel. At higher CuO nanoparticle contents (>1 wt%), the agglomeration of nanoparticles and their cytotoxic effects resulted in reduced antibacterial characteristics and MG63 …
... Although the coatings with only antifouling properties are able to reduce bacterial adhesion on the surfaces to a certain extent without killing them, their effect is usually not complete and has a short effective period of time. 6 On the other hand, the coatings with only antimicrobial activity are capable of effectively killing the attached microbes on the surface, but the dead cells and their debris often accumulate on the coating surfaces, thus obstructing their antimicrobial activity. 7 Therefore, the dual/multi-functional self-cleaning coatings with both antifouling and antimicrobial properties are highly desirable. ...
Biomaterial-associated infections caused by bacterial contamination and the subsequent formation of biofilms on the surfaces are challenging our healthcare system. In this work, povidone-iodine-functionalized fluorinated copolymers with stable antibacterial, antibiofilm, and antifouling activities were designed and prepared by a two-step synthesis. First, a series of poly(hexafluorobutyl methacrylate-co-N-vinyl-2-pyrrolidone), i.e., P(HFBMA-VP), were synthesized by radical copolymerization at different feed ratios to acquire water insoluble and antifouling copolymers. At the second step, the VP segments in the copolymer were complexed with iodine to obtain the objective antibacterial and antifouling copolymer P(HFBMA-VP)-I. The chemical and physical characteristics of the copolymers were investigated using 1H NMR, FTIR, XPS, EDX, UV-Vis, SEM, TEM, elemental analysis, and contact angle meter. P(HFBMA-VP)-I exhibited excellent antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus), as well as good biocompatibility towards human hepatocyte cells (L02) and Caenorhabditis elegans. Using electrospinning or spraying technique, P(HFBMA-VP)-I was coated on polystyrene slides, medical stainless steel sheets, and cotton fabric, allowing the surfaces to have stable antibacterial and antibiofilm activities against pathogenic bacteria and antifouling capability against foulants and blood, and exhibit excellent self-cleaning property.
... In order to overcome these issues, various types of polymeric (i.e. polycaprolacton (PCL) [9], chitosan [10] and polydimethylsiloxane (PDMS) [11]), ceramic (i.e. hydroxyapatite [3]) and nanocomposite (i.e. ...
With the advances in the development of biomaterials for tissue replacement, the attention of scientists has been focused on the improvement of clinical implant properties. In this regard, despite the appropriate properties of the stainless steel, the application of stainless steel as implants has been limited due to the weak corrosion resistivity. The purpose of this paper was preparation and characterization of hydrophobic polydimethylsiloxane (PDMS)-SiO2-CuO nanocomposite coating on the 316L stainless steel surface. The 316L stainless steel was coated by SiO2 nanoparticles (20 wt. %), CuO nanoparticles (0.5, 1 and 2 wt. %) and biocompatible PDMS. In this research, x-ray diffraction (XRD) and scanning electron microscopy (SEM) were applied to characterize the coating. Moreover, the roughness and water contact angle of the coatings consisting of various amounts of CuO nanopowder were estimated. Finally, the effects of various amounts of the CuO nanopowder on the corrosion resistivity of nanocomposite coatings were investigated. XRD patterns confirmed the presence of crystalline CuO nanoparticles on the substrate. Due to the non-crystalline nature of silica nanoparticles and the semi-crystalline PDMS polymer, no peak confirming the presence of these phases was detected on the XRD pattern of the nanocomposite coating. SEM images showed the formation of a lotus leaf-like layer on the surface of the nanocomposite coating containing 1 and 2 wt. % CuO. Moreover, water contact angle evolution revealed that while contact angle was 81 degree without CuO nanoparticles, it was enhanced to 146 degree in the presence of 1 wt. % CuO. Moreover, the corrosion study showed the nanocomposite containing 2 wt.% CuO had the best corrosion resistance, the corrosion current density of 2.1E-7 A.cm-2, and the corrosion potential of 0.22 V.
... The antimicrobial performance was quantified as MIC and MBC values, as listed in The lower MIC value against S. aureus compared to E. coli is consistent with studies which reported that polyQAS showed better bacteriostatic performance against Gram-positive compared to Gram-negative strains. [20][21][22][23][24][25] Although MeI-PDMAPMA possessed a stronger inhibition effect against S. aureus, the same value of MBC is required for the polymer against both strains. This means that disruption of the membrane of the two strains requires the same amount of polymer in solution, that is, same intensity of interaction between the polymer and the bacteria. ...
Antimicrobial polymers have been widely reported to exert strong biocidal effects against bacteria. In contrast with antimicrobial polymers with aliphatic ammonium groups, polymers with anilinium groups have been rarely studied and applied as biocidal materials. In this study, a representative polymer with aniline side functional groups, poly(N,N‐dimethylaminophenylene methacrylamide) (PDMAPMA), was explored as a novel antimicrobial polymer. PDMAPMA was synthesized and its physicochemical properties evaluated. The methyl iodide‐quaternized polymer was tested against the Gram‐positive Staphylococcus aureus, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 16–32 and 64–128 μg mL⁻¹, respectively. Against the Gram‐negative Escherichia coli, the MIC and MBC were both 64–128 μg mL⁻¹. To broaden the range of applications, PDMAPMA was coated on substrates via crosslinking to endow the surface with contact‐kill functionality. The effect of charge density of the coatings on the antimicrobial behavior was then investigated, and stronger biocidal performance was observed for films with higher charge density. This study of the biocidal behavior of PDMAPMA both in solution and as coatings is expected to broaden the application of polymers containing aniline side groups and provide more information on the antimicrobial behavior of such materials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019.
... 13−15 Therefore, numerous researchers have turned their attention to synthetic polymer mimics as AMP analogues to overcome these downfalls. To this end, a wide range of structures have been synthesized, including polyacrylates, 16,17 polymethacrylates, 14,18−21 polynorbornene derivatives, 22 polycarbonates, 23 polyacrylamides, 24 poly-(maleimide) analogues, 25 and cationic poly(benzyl ether)s. 26 For further structures and applications, readers are directed to reviews published. ...
There is growing interest in synthetic polymers which co-opt the structural features of naturally occurring antimicrobial peptides. However, our understanding of how macromolecular architecture affects antibacterial activity remains limited. To address this, we investigated whether varying architectures of a series of block and statistical co-oligomers influenced antibacterial and haemolytic activity. Cu(0)-mediated polymerization was used to synthesize oligomers constituting 2-(Boc-amino)ethyl acrylate units and either diethylene glycol ethyl ether acrylate (DEGEEA) or poly(ethylene glycol) methyl ether acrylate units with varying macromolecular architecture: subsequent deprotection produced primary amine functional oligomers. Further guanylation provided an additional series of antimicrobial candidates. Both chemical composition and macromolecular architecture were shown to affect antimicrobial activity. A broad spectrum antibacterial oligomer (containing guanidine moieties and DEGEEA units) was identified that possessed promising activity (MIC = 2 µg mL-1) towards both Gram-negative and Gram-positive bacteria. Bacterial membrane permeabilization was identified as an important contributor to the mechanism of action.
... 3 These polymers either possess inherent antimicrobial activity or are made antimicrobial through incorporation of organic or inorganic active agents. Examples of antimicrobial polymers belonging to the first class are chitosan, 4 poly-e-lysine, 5 quaternary ammonium polymers (e.g., cationic amphiphilic polycarbonates 6 ), polyguanidines, 7 polyethylenimine, 8 and halogen containing polymers (e.g., N-halamine). 9 Polymers possessing negligible or no antimicrobial activity can be modified to induce biocidal activity by addition of active antimicrobial agents. ...
Biomaterials based on non‐active polymers functionalized with antimicrobial agents by covalent modification or mixing are currently regarded as high potential solutions to prevent biomaterial associated infections that are major causes of biomedical device failure. Herewith a strategy is proposed in which antimicrobial materials are prepared by simply mixing‐and‐matching of ureido‐pyrimidinone (UPy) based supramolecular polymers with antimicrobial peptides (AMPs) modified with the same UPy‐moiety. The N‐terminus of the AMPs was coupled in solution to an UPy‐carboxylic acid synthon resulting in formation of a new amidic bond. The UPy‐functionalization of the AMPs did not affect their secondary structure, as proved by circular dichroism spectroscopy. The antimicrobial activity of the UPy‐AMPs in solution was also retained. In addition, the incorporation of UPy‐AMPs into an UPy‐polymer was stable and the final material was biocompatible. The addition of 4 mol % of UPy‐AMPs in the UPy‐polymer material protected against colonization by Escherichia coli, and methicillin‐sensitive and ‐resistant strains of Staphylococcus aureus. This modular approach enables a stable but dynamic incorporation of the antimicrobial agents, allowing at the same time for the possibility to change the nature of the polymer, as well as the use of AMPs with different activity spectra. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018
... Synthetic biodegradable polymers, such as aliphatic polyesters and polycarbonates, have attracted considerable attention in the field of biomedical and pharmaceutical applications. [1][2][3][4][5] Aliphatic polyester based materials are known to degrade in vivo by the bulk erosion process. 6,7 However, the generated acidic degradation products would cause local aseptic inflammation or living tissue injury and inactivate the loaded drugs. ...
In this work, poly(dimethylacrylamide)-b-poly(trimethylene carbonate) (PDMAAm-b-PTMC) block copolymers containing a pH-sensitive imine linkage were successfully synthesized by combination of ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. A variety of vanillin terminated PTMC were prepared by ROP of trimethylene carbonate (TMC) initiated by modified vanillin in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as organo-catalyst. Analysis of the resultant homopolymers by 1H NMR spectroscopy, size exclusion chromatography (SEC) and ESI-ToF masspectrometry (ESI-ToF-MS) revealed the excellent control of molar masses (Mn up to 14,000 g/mol), dispersities (ĐM < 1.15) and end groups. The PTMC homopolymer was subsequently end-capped with an amino functionalized RAFT-agent leading to a macroinitiator containing imine group. Using this macroinitiator PDMAAm-b-PTMC block copolymers with various molar masses were successfully prepared. In aqueous solution at pH 7.4, micelles could be formed by self-assembly of the amphiphilic block copolymer using a dialysis method. The hydrodynamic diameter (Dh) of the micelles was 76.3 ± 2.4 nm with polydispersity (PDI) of 0.179 ± 0.002. Under weak acidic condition (pH 6.0), the hydrophilic PDMAAm block could be cleaved from micelles by hydrolysis of the imine linkage, while PTMC nanoparticles formed in situ with an average size of 149.8 ± 4.5 nm (PDI = 0.287 ± 0.007). Based on our strategy, these pH-cleavable PTMC-based amphiphilic block copolymers will expand the range of biodegradable synthetic polymers available for potential biomedical applications, such as controlled drug and gene delivery.
... Due to their interesting thermal and mechanical properties, aliphatic Poly(carbonates) (PCs) find applications in a wide variety of fields, such as in regenerative medicine, drug delivery and in the coatings industry [25][26][27][28]. Furthermore, PCs typically present longer hydrolytic stability in water when compared to polyesters, are highly transparent to visible light and have a tunable and generally low T g value [29][30][31]. ...
Hydrophilic coatings have recently emerged as a new approach to avoiding the adhesion of (bio)organisms on surfaces immersed in water. In these coatings the hydrophilic character is crucial for the anti-fouling (AF) performance. However, this property can be rapidly lost due to the inevitable damages which occur at the surface, reducing the long-term effectiveness of the AF functionality. We report hydrophilic polycarbonate-poly(ethylene glycol) methyl ether (mPEG) polyurethane coatings with tunable hydrophilic properties as well as an excellent and long-term stability in water. The coatings exhibit low protein adhesion values and are able to self-replenish their hydrophilicity after damage, due to the existence of a reservoir of hydrophilic dangling chains incorporated in the bulk. The combination of low Tg and sufficient mobility of the mPEG dangling chains (enabled by chains with higher molecular weight) proved to be crucial to ensure autonomous surface hydrophilicity recovery when the coatings were immersed in water. This coatings and design approach offers new possibilities towards high-performance AF coatings with an extended service life-time which can be used in several major applications areas, such as marine and biomedical coatings, with major economic and environmental benefits.
... Triblock polycarbonate polymers composed of antifouling PEG, antimicrobial cationic polycarbonate, and a tethering or adhesive functional block have been synthesised and then covalently grafted on the catheter surface. Depending on the position of the adhesive block, the coatings demonstrated antibacterial and antifouling properties for both Gram-positive S. aureus and Gram-negative E. coli under conditions simulating the device lifetime (1 week) (Voo et al. 2015). Antimicrobial cationic polycarbonate/PEG hydrogels with strong broad-spectrum antimicrobial activities against clinically isolated multidrug-resistant microbes have been generated (Liu et al. 2012). ...
Drug resistance occurrence is a global healthcare concern responsible for the increased morbidity and mortality in hospitals, time of hospitalisation and huge financial loss. The failure of the most antibiotics to kill “superbugs” poses the urgent need to develop innovative strategies aimed at not only controlling bacterial infection but also the spread of resistance. The prevention of pathogen host invasion by inhibiting bacterial virulence and biofilm formation, and the utilisation of bactericidal agents with different mode of action than classic antibiotics are the two most promising new alternative strategies to overcome antibiotic resistance. Based on these novel approaches, researchers are developing different advanced materials (nanoparticles, hydrogels and surface coatings) with novel antimicrobial properties. In this review, we summarise the recent advances in terms of engineered materials to prevent bacteria-resistant infections according to the antimicrobial strategies underlying their design.
... The bacterial attachment and biofilm formation by S. aureus and E. coli on the surfaces were observed by FE-SEM. 54 Fresh bacteria at the logarithmic stage of growth were collected and resuspended (to OD 600 = 0.01) in MHB. The uncoated, poly (Ppep)-, and poly(Ppep/Psar)-coated PDMS films (1 × 1 cm 2 ) were individually immersed in 2 mL of the bacterial suspension and incubated at 37°C for 7 days to allow biofilm growth. ...
Methacrylate-ended polypeptides/polypeptoids (MePpep/MePsar) were successfully synthesized via ring-opening polymerization of N-carboxyanhydrides (NCAs). These oligomers were further initiated under ultraviolet (UV) irradiation by a polydopamine (pDA) layer which is attachable on virtually all materials surface to generate a polymer brush coating. This brush-like polymer coating comprising cationic antimicrobial polypeptides (MePpep) and antifouling polysarcosine (MePsar) exhibited effective antimicrobial activity against four pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans), as well as antifouling activity in the resistance to protein and platelet adhesion, and thus prevented biofilm formation for up to 7 days. An in vitro cytotoxicity study showed that this coating is biocompatible with mouse fibroblast (L929) cells. More importantly, this coating exhibited significant anti-infectivity in vivo. This dual-functional polymer brush coating can be immobili
... [10][11][12][13][14] Among these are selfassembling monolayers (SAMs), 5,12,15 polymer brushes based on PEG and zwitterionic moieties immobilized on different substrates [16][17][18][19][20] and the covalent introduction of PEG polymers based on click chemistry. 21,22 Moreover, PEG polymers can be anchored at different materials and substrates via the introduction of triblock copolymers, [23][24][25] in a supramolecular fashion by the post-modification of polymeric membranes based on cyclodextrin host-guest chemistry 26 or introduced at the surface of electrospun polyurethane (PU) fibers. 27 Additionally, multi-armed PEG polymers can be introduced at substrate surfaces to yield anti-fouling behavior. ...
Protein repellent coatings have been extensively studied to introduce anti-fouling properties at material surfaces. Here a covalent anti-fouling coating at the surface of supramolecular ureido-pyrimidinone (UPy) based materials introduced via post-modification of reactive UPy-functionalized tetrazine additives incorporated into the supramolecular polymer material. After material formulation, an anti-fouling coating comprised of bicyclononyne (BCN) functionalized poly (ethylene glycol) (PEG) polymers was reacted. This coating was covalently attached at the surface via a highly selective electron-demand Diels-Alder cycloaddition between tetrazine and BCN. The anti-fouling properties of three different BCN-PEG polymers, mono-functional-PEG-BCN, bi-functional-PEG-BCN and star-PEG-BCN, respectively, were systemetically studied. The mono-functional-PEG-BCN showed minor reduction in both protein adsorption and cell adhesion, whereas the bi-functional-PEG-BCN and the star-PEG-BCN polymer coating demonstrated complete anti-fouling performance, both towards protein adhesion as well as cell adhesion. Additionally, the bioorthogonal ligation strategy was performed in culture medium in the presence of cells showing similar behavior for the three anti-fouling coatings, which indicates this strategy can be applied for post-modification reactions in complex environment.
... All prepared silicone rubber surfaces were washed with 100% ethanol and distilled water three times each, followed by moist evaporation under nitrogen gas stream. 27 Polystyrene Surface Preparation. To prepare polystyrene surfaces for the polymer coating and contact angle measurements, Petri dishes were cut into uniform sizes (1.5 cm × 1.5 cm). ...
As reports of multidrug resistant pathogens have increased, patients with implanted medical catheters increasingly need alternative solutions to antibiotic treatments. As most catheter-related infections are directly associated with biofilm formation on the catheter surface, which, once formed, is difficult to eliminate, a promising approach to biofilm prevention involves inhibiting the initial adhesion of bacteria to the surface. In this study, we report an amphiphilic, antifouling polymer, poly(DMA-mPEGMA-AA) that can facilely coat the surfaces of commercially available catheter materials in water and prevent bacterial adhesion to and subsequent colonization of the surface, giving rise to an antibiofilm surface. The antifouling coating layer was formed simply by dipping a model substrate (polystyrene, PET, PDMS, or silicon-based urinary catheter) in water containing poly(DMA-mPEGMA-AA), followed by characterization by X-ray photoelectron spectroscopy (XPS). The antibacterial adhesion properties of the polymer-coated surface were assessed for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) growth under static (incubation in the presence of a bacterial suspension) and dynamic (bacteria suspended in a solution under flow) conditions. Regardless of the conditions, the polymer-coated surface displayed significantly reduced attachment of the bacteria (antiadhesion effect > ∼8-fold) compared to the bare noncoated substrates. Treatment of the implanted catheters with S. aureus in vivo further confirmed that the polymer-coated silicon urinary catheters could significantly reduce bacterial adhesion and biofilm formation in a bacterial infection animal model. Furthermore, the polymer-coated catheters did not induce hemolysis and were resistant to the adhesion of blood-circulating cells, indicative of high biocompatibility. Collectively, the present amphiphilic antifouling polymer is potentially useful as a coating platform that renders existing medical devices resistant to biofilm formation.
In recent years, the environmental problems accompanying the extensive application of biomedical polymer materials produced from fossil fuels have attracted more and more attentions. As many biomedical polymer products are disposable, their life cycle is relatively short. Most of the used or overdue biomedical polymer products need to be burned after destruction, which increases the emission of carbon dioxide (CO 2 ). Developing biomedical products based on CO 2 fixation derived polymers with reproducible sources, and gradually replacing their unsustainable fossil-based counterparts, will promote the recycling of CO 2 in this field and do good to control the greenhouse effect. Unfortunately, most of the existing polymer materials from renewable raw materials have some property shortages, which make them unable to meet the gradually improved quality and property requirements of biomedical products. In order to overcome these shortages, much time and effort has been dedicated to applying nanotechnology in this field. The present paper reviews recent advances in nanocomposites of CO 2 fixation derived reproducible polymers for biomedical applications, and several promising strategies for further research directions in this field are highlighted.
Clinical application of silicone rubber often encounters challenges. Here a strategy of free radical polymerization with 2-ethylhexyl acrylate (2-EHA) and maleic anhydride (MAh) to introduce durable crosslinked antimicrobial coating that covalently attached on silicone rubber substrate. The 2-EHA and MAh component endow the copolymer with good flexibility and further functionalization respectively. The copolymer coating is covalently bonded to the amine functionalized silicone rubber surface using a simple dip-coating technique and the thickness is adjustable. Poly (hexamethylene biguanide) (PHMB) is covalently coupled on the coating under mild conditions, and the immobilization density of PHMB is up to 3 mg cm⁻². The coating layer crosslinked by 1,4-butanediamine gas to enhance the durability of the coating and inhibit undesired swelling and remains intact after 500 bending cycles. The modified substrate exhibits excellent antibacterial activity, with 99.9% and 95.1% inhibition rate towards S. aureus and E. coli, respectively. It still maintained 96.2% of inhibition activity even after 12-day-long culturing with bacteria in simulated urine environment, exhibiting excellent long-term antibacterial stability. The results show that a simple, universal and scalable method to introduce antibacterial properties on polymer substrates, which also provides a new idea for the preparation of flexible cross-linking layers.
Biopolymer-based hydrophilic membranes with very high stability in aqueous systems were developed by using pectin as a non-toxic crosslinker. The unique properties of pectin as an efficient crosslinker were demonstrated using poly(vinyl alcohol) as a model for a highly water-soluble biopolymer. The chemical crosslinking strategy using glutaraldhehyde has proven successful in improving the stability of poly(vinyl alcohol) membranes. However, the use of non-toxic biological crosslinking agents has not been fully explored. We hypothesized that pectin, as a biopolymer bearing numerous carboxyl groups, could be a very efficient crosslinker compared to carboxylic acids, promoting unprecedented membrane stability. A systematic characterization of the chemical, thermal, mechanical, and functional properties of membranes prepared from poly(vinyl alcohol) crosslinked with pectin confirmed the excellent stability of the membranes in water, tested at the boiling point and at acidic and basic pH. The use of pectin also resulted in membranes with very high tensile strength, resistance to microbial degradation, antiradical and antibacterial activity, and improved water vapor barrier properties.
In this study, we report the facile surface modification of reverse osmosis (RO) membranes for improved filtration as
well as bacterial resistance properties. Thin films of two silanes, 3-aminopropyltriethoxysilane (3-APS) and 6-aminohexylaminotriethoxysilane (6-AHAS), were dip-coated on commercial RO membranes, and their nitrogen atoms subsequently
quaternized. Analyses of the modified membranes via scanning electron microscopy, Fourier transform infrared, and X-ray
photoelectron spectroscopy confirmed the “peak and valley” morphology of the original membrane, silane deposition, and N
quaternization, respectively. The original membrane showed a water contact angle of ∼90−100° that was significantly decreased
after silane coating: 63° for 3-APS and ∼52° for 6-AHAS. Filtration experiments with a high-salinity feed revealed significant
improvements in the permeate flux (∼25−40%) and salt rejection (∼10−15%) after the surface modification. Bacterial adhesion
studies with two different species, Bacillus subtilis and Pseudomonas aeruginosa, showed significantly reduced cell attachment on the
modified membranes. In addition, the coated and quaternized membranes significantly restricted the biological activity and colony
formation of both strains with a bacteriostasis rate of ∼75%. The enhanced filtration and antifouling capabilities of the modified
membranes were attributed to the presence of polar functionalities (R4N+).
A novel g-C3N4@InVO4 semiconductor catalyzed surface-initiated photo atom transfer radical polymerization without catalysts residues problem has been developed. This method proceeded in N-methyl pyrrolidone/aqueous under atmospheric conditions. To verify the versatility of this method and enhance the antifouling properties of polyvinyl alcohol (PVA) hydrogel, two types of fluorinated polymer brushes (p6F/p13F) were successfully constructed on PVA hydrogel surface instead of the subsurface. The chemical bonds between PVA matrix and fluorinated polymer brushes (p6F/p13F) enhanced the surface cross link density and resulted in an increase of thermal stability and mechanical properties. All fluorinated PVA hydrogels demonstrated excellent antifouling properties to tackle the biofouling problem in complex environment of the human body. In addition, all fluorinated PVA hydrogels was no cytotoxicity for L929 and NDHF according to ISO 10993.5:2009. g-C3N4@InVO4 catalyzed SI-photoATRP provides a novel surface modification technology for various biological or medical materials in the industrial-scale application.
Currently, it is highly desirable to develop a novel antifouling resin with a controllable hydrolysis rate and stable and effective antifouling performance for marine antifouling coatings. In our study, we prepared natural rosin-based zinc (RZn-x) resins by a relatively facile and green synthetic method from Zn(OH)2 and antimicrobial natural rosin, which is considered a toxicity-free raw material, thus ensuring the green and antimicrobial character of the material. In their optimal combination, the RZn-x coating surface exhibited ideal peeling behaviour upon immersion in seawater, which caused the WCA of the material surface to change from 55° before immersion to 135° after immersion for 60 days and enhanced the antifouling properties. Dynamic simulation experiments of these resins also demonstrated that the hydrolysis rate of this material immersed in dynamic seawater was related to the zinc content, and we could control the self-polishing ability of the resins by adjusting the content of Zn(OH)2 participating in the reaction. Moreover, hydrolysis led to a hydrophobic surface, which could prevent fouling organisms from adhering. Laboratory bioassays against BSA adsorption (immersed for 4 h: 1.986 μg/cm²), bacterial (over 95 % reduction) and marine algal adhesion (more than 60 % reduction) revealed outstanding anti-protein, bacteriostasis and anti-algal growth and adhesion properties compared to pure rosin and the control sample. The long-term antifouling capability in marine field tests indicated that the RZn-x resins maintained their antifouling activity for more than 6 months, especially RZn-50, which showed excellent antifouling performance.
Aliphatic polycarbonates have gained increased attention as biomaterials largely owing to their biocompatibility and tunable degradation. Moreover, the ability to introduce functional handles in the polymer backbone through careful design of cyclic carbonate monomers or copolymerization with other biodegradable polymers has significantly contributed to the interest in exploiting this class of materials for biomedical applications. Such investigations have enabled their utility to be expanded to a wide variety of applications in the biomedical field, from drug delivery to tissue regeneration and the design of vascular grafts. Herein, we review the synthesis, degradation, and studies into biomedical applications of aliphatic polycarbonates obtained by ring-opening polymerization of cyclic carbonate monomers (ring sizes between 6 and 8). While all synthetic methods will be covered, particular emphasis will be given to materials that have been exploited for therapeutic applications in vitro and in vivo.
Bacterial infections associated with biomedical devices and implants have posed a great challenge to global healthcare systems. These infections are mainly caused by bacterial biofilm formed on the surface of biomaterials, protecting the encapsulated bacteria from conventional antibiotic treatment and attack of the immune system. As the bacterial biofilm is difficult to eradicate, bactericidal and antifouling coatings have emerged as promising strategies to prevent biofilm formation and subsequent infections. Hydrogels with three-dimensional crosslinked hydrophilic networks, tunable mechanical property and large drug-loading capacity are desirable coating materials, which can kill bacteria and/or prevent bacterial adhesion on the surface, inhibiting biofilm formation. Herein, we review recent developments of hydrogels as anti-infective coatings. Particularly, we highlight two chemical approaches (graft-from and graft-to), which have been used to immobilize hydrogels on surfaces, and present advances in the development of bactericidal (contact-killing and antimicrobial-releasing), antifouling (hydrophilic polymer network) and bifunctional hydrogel coatings with both bactericidal and antifouling activities. In addition, the challenges of hydrogel coatings for clinical applications are discussed, and future research directions of anti-infective hydrogel coatings are proposed.
Tackling fogging and microbial infection problems related to the endoscope lens remain challenges due to visual disturbances and bacterial threats to human health. Herein, highly transparent antifogging and antibacterial coatings were developed in a facile way by thermal curing of zwitterionic copolymers poly(n-butyl methacrylate-co-2-aminoethyl methacrylate-co-sulfobetaine methacrylate)s with 1,3,5-triformylbenzene. Characterizations of surface chemical composition and wettability suggested that the copolymer coatings exhibited amphiphilicity with a hydrophobic surface and internal hydrophilicity. The prepared amphiphilic coating exhibited excellent antifogging properties both in vivo and in vitro. The introduction of hydrophobic n-butyl methacrylate and cationic aminoethylmethacrylate could improve the stability and antibacterial capability of the coating. The growth inhibition rates of the coatings against Staphylococcus aureus and Escherichia coli were up to 99% and the copolymer coatings with the zwitterionic groups had low hemolytic rates less than 3%. The amphiphilic copolymer coatings combined antifogging and antibacterial properties may have a promising potential for applications in biomedical devices.
Creating hierarchical polymer brushes possessing the antifouling and bactericidal functionalities is a promising approach to combat biomaterial-associated infections. Hence, a well-constructed hierarchical structure is required to obtain the optimized antibacterial performance. In this work, contact-killing cationic bactericidal poly(quaternary ammonium salts) (PQAs) bearing different alkyl chain lengths and zwitterionic antifouling poly(sulfobetaine methacrylate) (PSBMA) functional segments were grafted onto the activated substrate via surface-initiated atom transfer radical polymerization (SI-ATRP), and three kinds of polymer brushes with different architectures (Si-PQAs-b-PSBMA, Si-PSBMA-b-PQAs and Si-PQAs-r-PSBMA) were constructed. We demonstrate that the antibacterial effect simultaneously depends on the alkyl chain lengths of PQAs and the hierarchical structure of cationic/zwitterionic segments in polymer brushes. When the polymer brushes composed of a bactericidal bottom layer and an antifouling top layer, the ideal alkyl chain length of PQAs should be eight carbon atoms (Si-PQA8C-b-PSBMA), while in the opposite hierarchical structure, the optimized alkyl chain length of PQAs to synergize with PSBMA was four carbon atoms (Si-PSBMA-b-PQA4C). By appropriately adjusting the alkyl chain length or the hierarchical architecture, the interference between the antifouling and bactericidal functions could be avoided, thus achieving the outstanding long-term antibacterial performance against S. aureus, as well as good hemocompatibility and low cytotoxicity. This work provides fundamental guidance for the design and optimization of efficient and reliable antibacterial surfaces to inhibit biofilm formation.
Owing to the biodegradability and good biocompatibility polycarbonates show the versatile class of applications in biomedical fields. While their poor functional ability seriously limited the development of functional polycarbonates. Herein, a new Br‐containing cyclic carbonate (MTC‐Br) and a polycarbonate atom transfer radical polymerization (ATRP) macro‐initiator (PEG‐PMTC‐Br) is synthesized. Then, by initiating the side‐chain ATRP of 2‐(dimethyl amino)ethyl methacrylate (DMAEMA) on PEG‐PMTC‐Br, a series of comb‐like amphiphilic cationic polycarbonates, PEG‐b‐(PMTC‐g‐PDMAEMA) (GMDMs), with different lengths of cationic branches are successfully prepared. All these poly(ethylene glycol)‐b‐(poly((5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐yl) methyl 2‐bromo‐2‐methylpropanoate/1,3‐dioxane‐2‐one)‐g‐poly(2‐dimethyl aminoethyl methacrylate) (GMDMs) self‐assembled nanoparticles (NPs) (≈180 nm, +40 mV) can well bind siRNA to form GMDM/siRNA NPs. The gene silence efficiency of GMDM/siRNA high to 80%, which is even higher than the commercial transfection reagent lipo2000 (76%). But GMDM/siRNA shows lower cell uptake than lipo2000. So, the high gene silence ability of GMDM/siRNA NPs can be attributed to the strong intracellular siRNA trafficking capacity. Therefore, GMDM NPs are potential siRNA vectors and the successful preparation of comb‐like polycarbonates also provides a facile way for diverse side‐chain functional polycarbonates, expanding the application of polycarbonates. In this study, a new Br‐containing cyclic carbonate MTC‐Br and a polycarbonate ATRP macroinitiator (PEG‐PMTC‐Br) are first synthesized successfully. Then a series of comb‐like polycarbonates with the different cationic length of cationic branches, PEG‐b‐(PMTC‐g‐P(DMAEMA)) (GMDM), are prepared for siRNA delivery. This design shows the GMDM/siRNA nanoparticles have 80% gene silence efficiency, which is even higher than commercial transfection reagent lipo2000 (76%) .
Endoscopic surgery has gained widespread applications in various clinical departments, and endoscope surfaces with antifogging and antibacterial properties are essential for elaborate procedures. In this work, novel antifogging/antibacterial coatings were developed from a cationic copolymer and a hydrophilic copolymer, polyhedral oligomeric silsesquioxane-poly(quaternary ammonium compound-co-2-aminoethyl methacrylate hydrochloride) (POSS-P(QAC-co-AEMA)) and poly(N-hydroxyethylacrylamide-co-glycidyl methacrylate) (P(HEAA-co-GMA)), via a facile and green blending method. Such transparent coatings showed excellent antifogging performance under both in vitro and in vivo fogging conditions, mainly attributed to the high water-absorbing capability of HEAA and QAC. Antibacterial assays proved that the blending coatings had superior antibacterial property, which could be improved with the proportion of POSS-P(QAC-co-AEMA) due to the bactericidal efficiency of cationic QAC. Meanwhile, owing to the high hydratability of HEAA, the blending coatings exhibited bacteria-repelling property. By simply tuning the blending ratio of POSS-P(QAC-co-AEMA) and P(HEAA-co-GMA), the comprehensive bacteria-killing and bacteria-repelling properties of the coatings were achieved. Moreover, after incubating with red blood cells, the prepared blending coatings presented lower hemolytic rate of less than 5%. The findings provided a potential means for addressing the challenge of fogging and bacterial contamination occurred in endoscopic lens and other medical devices.
Bacterial pathogens are responsible for millions of cases of illnesses and deaths each year throughout the world. The development of novel surfaces and coatings that effectively inhibit and prevent bacterial attachment, proliferation, and growth is one of the crucial steps for tackling this global challenge. Herein, we report a dual-functional coating for aluminum surfaces that relies on the controlled immobilization of lysozyme enzyme (muramidase) into interstitial spaces of presintered, nanostructured thin film based on ∼200 nm silica nanoparticles and the sequential chemisorption of an organofluorosilane to the available interfacial areas. The mean diameter of the resultant lysozyme microdomains was 3.1 ± 2.5 μm with an average spacing of 8.01 ± 6.8 μm, leading to a surface coverage of 15.32%. The coating had an overall root-mean-square (rms) roughness of 539 ± 137 nm and roughness factor of 1.50 ± 0.1, and demonstrated static, advancing, and receding water contact angles of 159.0 ± 1.0°, 155.4 ± 0.6°, and 154.4 ± 0.6°, respectively. Compared to the planar aluminum, the coated surfaces produced a 6.5 ± 0.1 (>99.99997%) and 4.0 ± 0.1 (>99.99%) log-cycle reductions in bacterial surfaces colonization against Gram-negative Salmonella Typhimurium LT2 and Gram-positive Listeria innocua, respectively. We anticipate that the implementation of such a coating strategy on healthcare environments and surfaces and food-contact surfaces can significantly reduce or eliminate potential risks associated with various contamination and cross-contamination scenarios.
Biocompatible poly(ε-caprolactone) (PCL) was definitely endowed with antibacterial efficiency via blending with cationic − zwitterionic block copolymers of 2-(dimethylamino)ethyl methacrylate and sulfobetaine methacrylate (pDMA-b-pSBMA). The involved pDMA-b-pSBMA, obtained via reversible addition-fragmentation chain transfer polymerization, was prominent with well-defined structure and efficient antibacterial ability. In dip coatable PCL/pDMA-b-pSBMA blends, the zwitterionic moiety was detected prior in migration towards the surface, which favored passive function of anti-bacterial adhesion. The antibacterial abilities of the blends against Escherichia coli and Staphylococcus aureus were significant, which evolved with the surface morphology, composition and wettability, and were demonstrated with membrane disruption and/or permeabilization mechanism. The relative cell viability of the surface for vascular smooth muscle cells was around 80%, while the hemolysis of all the blends was lower than 2%. Derived from popular matrix of PCL and cationic − zwitterionic copolymer, the blends are endowed with antibacterial ability as well as biocompatibility, presenting potential for biomedical devices.
In recent years, continuous and stable antibacterial ability has received extensive attention in the field of antibacterial composite materials. The researchers expect a kind of antibacterial composites with continuous and stable antibacterial acting and good biocompatibility. Herein we used a unique in-situ modification methods which inspired self-polymerization of dopamine to fix the nano-Ag on the bacterial cellulose (BC). The antibacterial properties of composites were tested in two new methods (antibacterial stability and antibacterial durability). We researched the cause of the antibacterial properties by analyzing the valence state and binding energy of Ag. The chelation between PDA and Ag is considered to the key to stable release of Ag⁺. The three-dimensional network of BC is also thought to play some role in making Ag⁺ release stability. Moreover, PDA as a reducing agent, reacting with Tollens reagent to produce nano-Ag nanoparticles, is a good method for reducing the toxicity of nano-Ag and enhancing the biological compatibility of composites. Our results hence illustrate that the BC antimicrobial composites by PDA in-situ reduction nano-Ag has a great potential as an antibacterial dressing with stable antimicrobial properties and biocompatibility.
The colonization of undesired bacteria on the surface of devices used in biomedical and clinical applications has become a persistent problem. Different types of single-function (cell resistance or bactericidal) bioresponsive materials have been developed to cope with this problem. Even though these materials meet the basic requirements of many biomedical and clinical applications, dual-function (cell resistance and biocidal) bioresponsive materials with superior design and function could be better suited for these applications. The past few years have witnessed the emergence of a new class of dual-function materials that can reversibly switch between cell-resistance and biocidal functions in response to external stimuli. These materials are finding increased applications in biomedical devices, tissue engineering, and drug-delivery systems. This review highlights the recent advances in design, structure, and fabrication of dual-function bioresponsive materials, and discusses translational challenges and future prospects for research involving these materials.
A series of fluorinated polyurethane (FPU) with different content of fluorinated chain extenders (EF) and the same amount of PTMG and MDI have been synthesized in this study to explore the relationship between the surface physicochemical properties, bulk microphase separation structures of these FPUs and their antifouling activities against model bacteria and platelets. The bulk microphase separation of FPUs increased with the amount of EF incorporated in. It was found that all the surface of FPUs were saturated by a layer of fluorocarbon chains which resulted the similar chemical composition and wetting activities for the three kinds of FPUs. The FPUs with lower or similar microphase separation compared with non fluorinated PU which was chain extended by BDO showed similar or even increased adhesion of bacteria and platelet. Notable, FPU with a higher degree of microphase separation than non fluorinated PU displayed excellent antifouling activities against both model bacteria and blood platelet. It is therefore concluded that the increased microphase separation of the fluorinated PUs results in enhanced antifouling properties.
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Most synthetic antimicrobial polymers are not biodegradable, thus limiting their potential for large-scale applications in personal care disinfection and environmental contaminations. Poly(ϵ-caprolactone) (PCL) is known to be both biodegradable and biocompatible, thus representing an ideal candidate biopolymer for antimicrobial applications. Here we successfully grafted alkylimidazolium (Im) onto PCL to mimic the cationic properties of antimicrobial peptides. The poly(ϵ-caprolactone)-graft-butylimidazolium had only moderate MICs (32 μg/mL), reasonably good red blood cell selectivity (36) and relatively good fibroblast compatibility (81% cell viability at 100 μg/mL), indicating that combining the hydrophobic PCL backbone with the most hydrophilic butylimidazolium gives a good balance of MIC and cytotoxicity. On the other hand, the PCL-graft-hexylimidazolium and -octylimidazolium demonstrated better MICs (4-32 μg/mL), but considerably worse cytotoxicity. We postulated that the worse hydrophilicity of hexylimidazolium and octylimidazolium was responsible for their higher cytotoxicity and sought to moderate their cytotoxicity with different sugar compositions and lengths. Through our screening, we identified a candidate polymer, P(C6Im)0.35CL-co-P(Man)0.65CL, that demonstrated both superior MIC and very low cytotoxicity. We further demonstrated that our biopolymer hit had superior antimicrobial kinetics compared to the antibiotic vancomycin. This work paves the way forward for the use of biodegradable polyesters as the backbone scaffold for biocompatible antibacterial agents, by clicking with different types and ratios of alkylimidazolium and carbohydrate moieties.
Abstract
The purpose of this paper was to develop the hydrophobic nanocomposite coatings of polydimethylsiloxane (PDMS)-SiO2-CuO to improve biocompatibility, corrosion resistance and antibacterial property of 316 L stainless. In this research, after synthesize of CuO and SiO2 nanopowders using wet-chemical approaches, PDMS-SiO2-CuO coatings consisting of various amounts of CuO nanoparticles were developed using dip-coating process. The nanocomposite coatings were characterized with regard to the structural and physical properties, corrosion resistance, antibacterial activity and cellular interactive responses. The results showed that incorporation of CuO nanoparticles <2 wt% improved the corrosion resistance of 316 L stainless steel. At higher CuO nanoparticle contents (>1 wt%), the agglomeration of nanoparticles and their cytotoxic effects resulted in reduced antibacterial characteristics and MG63 cell viability and proliferation. In summary, PDMS-SiO2-CuO nanocomposite coating with significant antibacterial and anticorrosion behavior could be a promising coating for biomedical implants.
Cationic polycarbonates are a class of very important polymers owing to their positively charged moieties and biodegradability. The positively charged moieties in cationic polycarbonates are able to combine anionic compounds such as nucleic acids and proteins to form the polyplexes. The biodegradability of cationic polycarbonates can reduce their toxicity. Here we summarized the reports on cationic polycarbonates via ring-opening polymerization from design and synthesis to applications. The synthetic methods of cationic polycarbonates mainly include ring-opening polymerization of cyclic carbonates containing amino groups and amination of functional polycarbonates. Cationic polycarbonates have been widely applied in biomedical fields such as drug release, gene delivery, and antimicrobial polymers.
Carbohydrates are the fundamental building blocks of many natural polymers, their wide bioavailability, high chemical functionality, and stereochemical diversity make them attractive starting materials for the development of new synthetic polymers. In this work, one such carbohydrate, d‐glucopyranoside, was utilized to produce a hydrophobic five‐membered cyclic carbonate monomer to afford sugar‐based amphiphilic copolymers and block copolymers via organocatalyzed ring‐opening polymerizations with 4‐methylbenzyl alcohol and methoxy poly(ethylene glycol) as initiator and macroinitiator, respectively. To modulate the amphiphilicities of these polymers acidic benzylidene cleavage reactions were performed to deprotect the sugar repeat units and present hydrophilic hydroxyl side chain groups. Assembly of the polymers under aqueous conditions revealed interesting morphological differences, based on the polymer molar mass and repeat unit composition. The initial polymers, prior to the removal of the benzylidenes, underwent a morphological change from micelles to vesicles as the sugar block length was increased, causing a decrease in the hydrophilic–hydrophobic ratio. Deprotection of the sugar block increased the hydrophilicity and gave micellar morphologies. This tunable polymeric platform holds promise for the production of advanced materials for implementation in a diverse range of applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018
Smart materials with both bactericidal and bacteria-resistant functions are promising to combat the infection concern of medical devices. Current work mostly utilizes hydrolysis to switch materials from antimicrobial to antifouling forms, by incubating materials in aqueous solutions for hours to days. In this work, a new photoresponsive poly[2-((4,5-dimethoxy-2-nitrobenzyl)oxy)-N-(2-(methacryloyloxy)ethyl)-N,N-dimethyl-2-oxoethan-1-aminium] (polyCBNA) hydrogel was developed, incorporating the photolabile 4,5-dimethoxy-2-nitrobenzyl and the cationic quaternary ammonium groups. The photolabile groups were readily cleaved from the hydrogel shortly upon UV irradiation at 365 nm (a long wavelength widely used for biomedical applications), leading to polymer surface charge switching from cationic to zwitterionic form. Protein adsorbed significantly on polyCBNA, but easily desorbed from surfaces after UV irradiation. The cationic hydrogel as a precursor was shown to effectively kill the attached bacteria, then quickly switched to zwitterionic antifouling form via photolysis, which released the attached bacteria from surfaces and prevented further bacterial attachment. Moreover, the adhered endothelial cells were easily detached from polyCBNA surfaces triggered by light, providing a facile and less destructive non-enzymatic approach to harvest cells. This smart photoresponsive polyCBNA polymer, with integrated antimicrobial and antifouling properties, holds great potential in biomedical applications such as self-sterilizing and self-cleaning coatings for implants, cell harvesting, and cell patterning.
Integrated antibacterial and antifouling surfaces in favor of avoiding implant-related infections are necessarily required for biomaterials when they contact with the body fluid. In this work, an antibacterial and antifouling membrane was developed via cross-linking chitosan-g-eugenol and the zwitterionic copolymer poly(sulfobetaine methylacrylate-co-2-aminoethyl methacrylate) on the electrospun polycarbonate urethane substrate using genipin as a cross-linker. Antibacterial assays demonstrated that the prepared membranes had efficient antibacterial activity with 92.8 ± 2.5% and 95.2 ± 1.3% growth inhibition rates against Escherichia coli and Staphylococcus aureus, respectively. The investigations on antifouling activity and hemocompatibility of the membranes showed significant resistances to bacterial attachment, non-specific protein adsorption and platelet adhesion, and presented lower hemolytic activity and good anticoagulant activity as well. Moreover, cell culture assays indicated that the prepared membranes exerted no obvious cytotoxicity with more than 80% of relative L929 fibroblast viability. Therefore, the membranes with integrated antibacterial and antifouling properties could be potentially applied in promising indwelling devices.
A novel approach for preparing self-cleaning anti-fouling surfaces with compositional heterogeneous polymer brushes at a molecular-length scale was developed. The approach exploits three critical elements including hydrophilic poly(ethylene glycol) (PEG) brushes with non-fouling functionality, self-cleaning fouling-release hydrophobic poly(2,2,3,3,3-pentafluoropropyl acrylate) (PPFA) brushes and catechol moieties, an important component of mussel adhesive proteins (MAPs), to anchor asymmetric polymer brushes onto surfaces. Well-defined PtBBPMA-co-PPEGMEMA-co-PDOMA macroinitiators were first prepared by RAFT copolymerization of tert-butyl 2-((2-bromopropanoyloxy)methyl)acrylate (tBBPMA) bearing a Br-containing ATRP initiating group, poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) macromonomer, and N-(3,4-dihydroxy- phenethyl) methacrylamide (DOMA) with an adhesive anchoring group of catechol moiety. The target asymmetric polymer brushes were obtained by ATRP of PFA initiated by the macroinitiator via the grafting-from strategy. By using the drop coating method, the asymmetric polymer brush surface could form a layer of amphiphilic brushes onto the substrate with the assistance of adhesive anchoring groups. With dense heterogeneous brush conformation at a molecular-length scale, (PtBA-co-PPEGMEMA-co-PDOMA)-g-PPFA-based surface shows considerable self-cleaning anti-fouling performance with less protein adsorption (up to 93% off) and cell adhesion (up to 88% off) compared to bare surface.
Aliphatic polycarbonates are promising materials in the biomedical field due to their low toxicity, biocompatibility, and biodegradability. A popular approach in obtaining these materials is through the organocatalyzed ring-opening polymerization (ROP) of cyclic carbonates. Functional polycarbonates can be obtained by (co)polymerizing allyl functional cyclic monomers, which can be chemically modified via radical thiol-ene click reactions after the ROP process. To date, allyl bearing 6-membered cyclic carbonates have been reported, however their polymerization kinetics are slow. In previous works, larger cyclic carbonates (e.g. N-substituted eight membered cyclic carbonates) have demonstrated superior reactivites over their smaller counterparts and hence, in this work, we investigated the preparation and ROP of two allyl bearing N-substituted eight membered cyclic carbonates. One of these monomers, with a pendent carbamate group, displayed substantially enhanced polymerization kinetics that allowed for efficient homopolymerizations and co-polymerizations with commercially available monomers (e.g. trimethylene carbonate, or TMC). Lastly, the polymers underwent almost quantitative post-polymerization modification via thiol-ene chemistry to yield different functionalized polycarbonates. We also demonstrated that the post-polymerization reaction could be used to form polycarbonate-based gels with multifunctional thiols.
Confronted with the risk of stenosis and bacterial infection, vascular grafts are necessarily required with rapid endothelialization and antibacterial activity. In this work, dual-functional electrospun membranes of poly(ε-caprolactone) (PCL)/gelatin were developed. A short active peptide, REDV, was covalently conjugated with a low molecular weight PCL to obtain REDV-PCL-REDV, which was introduced into the electrospun fibers to improve the adhesion and proliferation of vascular endothelial cells (VECs) on the electrospun membranes. Additionally, a plant-extracted antibacterial agent, eugenol, was loaded for the antibacterial purpose. Results suggested that the electrospun membranes demonstrated acceptable mechanical properties and release profiles. The electrospun membrane containing 30% of eugenol could inhibit Escherichia coli and Staphylococcus aureus with 71.6±3.3% and 78.6±2.5% of growth inhibition rates, respectively. Further results showed all the electrospun membranes exhibited lower cytotoxicity towards L929 fibroblasts with more than 80% of relative cell viability. The VEC culture assays indicated that the REDV-modified electrospun membranes by the incorporation of REDV-PCL-REDV could significantly promote VEC adhesion and proliferation. Therefore, the dual-functional electrospun membranes with endothelialization and antibacterial abilities by incorporating REDV and eugenol could be potentially applied as promising vascular grafts.
In this work, antibacterial and anti-adhesive polymeric thin films were constructed on polyacrylonitrile (PAN) nanofibrous membranes in order to extend their applications. Polyhexamethylene guanidine hydrochloride (PHGH) as an antibacterial agent and heparin (HP) as an anti-adhesive agent have been successfully coated onto the membranes via a layer-by-layer (LBL) assembly technique confirmed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM). The antibacterial properties of LBL-functionalized PAN nanofibrous membranes were evaluated using the Gram-positive bacterium Staphylococcus aureus and the Gram-negative Escherichia coli. Furthermore, the dependence of the antibacterial activity and anti-biofouling performance on the number of layers in the LBL films was investigated quantitatively. It was found that these LBL-modified nanofibrous membranes possessed high antibacterial activities, easy-cleaning properties and stability under physiological conditions, thus qualifying them as candidates for anti-biofouling coatings.
A novel strategy to synthesize and functionalize maleimide containing thiol reactive biodegradable polymers by the organocatalyzed (co)polymerization of a novel furan-protected maleimide-functional carbonate monomer was described. The furan-protected maleimide-containing cyclic carbonate monomer was synthesized using the protected diol. Monitoring the monomer conversion with time in the DBU catalyzed homopolymerization revealed that the polymerization became retarded at ca. 60% monomer conversion, likely a consequence of the ring-chain equilibrium associated with sterically hindered monomers. The retro Diels-Alder reaction partially occurs upon ionization by the laser. Following exposure of the furan-protected copolymers to high vacuum at 100°C, the efficiency of the rDA reaction was clearly evident from the 1H NMR spectra of the polymers observing a complete disappearance of the resonances.
A wide range of biomedical devices is applied clinically in contact with blood. Tailoring the surface properties of the involved biomaterials is a common approach to enhance performance and to limit adverse reactions. This review summarizes current trends in coating technologies developed for that purpose. Inorganic coatings were shown to substantially improve the durability and inertness of biomaterials while a number of advanced polymer coatings were demonstrated to be very effective by targeting specific biochemical pathways. However, to fully utilize the power of these bioactive coatings safety issues need to be thoroughly addressed in future studies.
The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated-infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice showed bioluminescence and were culture-positive. In an antibiotic treated group, no bioluminescence was detected and only 20% of all primary implants and no tissue samples were culture-positive. After revision surgery, bioluminescence was detected in all control mice. All the implants and 80% of all tissue samples were culture-positive. In contrast, in the antibiotic treated group, 17% of all secondary implants and 33% of all tissue samples were culture-positive, despite antibiotic treatment. The study illustrates that due to the BAI of a primary implant, the infection risk of biomaterial implants is higher in revision surgery than in primary surgery, emphasizing the need for full clearance of the infection, as well as from surrounding tissues prior to implantation of a secondary implant.
Biofilm-associated infections in trauma surgery are difficult to treat with conventional therapies. Therefore, it is important to develop new treatment modalities. Maggots in captured bags, which are permeable for larval excretions/secretions, aid in healing severe, infected wounds, suspect for biofilm formation. Therefore we presumed maggot excretions/secretions would reduce biofilm formation.
We studied biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella oxytoca, Enterococcus faecalis, and Enterobacter cloacae on polyethylene, titanium, and stainless steel. We compared the quantities of biofilm formation between the bacterial species on the various biomaterials and the quantity of biofilm formation after various incubation times. Maggot excretions/secretions were added to existing biofilms to examine their effect.
Comb-like models of the biomaterials, made to fit in a 96-well microtiter plate, were incubated with bacterial suspension. The formed biofilms were stained in crystal violet, which was eluted in ethanol. The optical density (at 595 nm) of the eluate was determined to quantify biofilm formation. Maggot excretions/secretions were pipetted in different concentrations to (nonstained) 7-day-old biofilms, incubated 24 hours, and finally measured.
The strongest biofilms were formed by S. aureus and S. epidermidis on polyethylene and the weakest on titanium. The highest quantity of biofilm formation was reached within 7 days for both bacteria. The presence of excretions/secretions reduced biofilm formation on all biomaterials. A maximum of 92% of biofilm reduction was measured.
Our observations suggest maggot excretions/secretions decrease biofilm formation and could provide a new treatment for biofilm formation on infected biomaterials.
Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.
Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
Two quaternary ammonium silanes (QAS) were used to coat silicone rubber tracheoesophageal shunt prostheses, yielding a positively charged surface. One QAS coating [(trimethoxysilyl)-propyldimethyloctadecylammonium chloride] was applied through chemical bonding, while the other coating, Biocidal ZF, was sprayed onto the silicone rubber surface. The sprayed coating lost its stability within an hour, while the chemically bonded coating appeared stable. Upon incubation in an artificial throat model, allowing simultaneous adhesion and growth of yeast and bacteria, all coated prostheses showed significant reductions in the numbers of viable yeast (to 12% to 16%) and bacteria (to 27% to 36%) compared with those for silicone rubber controls, as confirmed using confocal laser scanning microscopy after live/dead staining of the biofilms. In situ hybridization with fluorescently labeled oligonucleotide probes showed that yeasts expressed hyphae on the untreated and Biocidal ZF-coated prostheses but not on the QAS-coated prostheses. Whether this is a result of the positive QAS coating or is due to the reduced number of bacteria is currently unknown. In summary, this is the first report on the inhibitory effects of positively charged coatings on the viability of yeasts and bacteria in mixed biofilms. Although the study initially aimed at reducing voice prosthetic biofilms, its relevance extends to all biomedical and environmental surfaces where mixed biofilms develop and present a problem.
Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.
A series of brush-like polycarbonates containing all three key components, namely a pendent dopamine, short chain PEG, and antibacterial cations for electrostatic targeting of bacteria as well as membrane lysis, were synthesized with precise control over molecular composition by organocatalytic ring-opening polymerization (ROP). The bio-inspired adhesive moiety was conjugated to the polycarbonate via facile chemistry to provide catecholamines, which mimics the side chain chemistry of the repetitive di-peptide of 3,4-dihydroxy-L-phenylalanine (DOPA, Y)-histidine (H) in the adhesive catecholamine. The brush-like polycarbonates were synthesized by copolymerization of a cyclic carbonate monomer containing a pendent benzyl chloride group (MTC-BnCl) with a cyclic carbonate monomer containing a pendent short chain PEG group (MTC-PEG using 4-methylbenzyl alcohol (4-MBA) as the initiator, and N-(3,5-trifluoromethyl)phenyl-N'-cyclohexylthiourea (TU)/1,8-diazabicyclo[5,4,0]undec-7-ene) (DBU) as co-catalysts to facilitate polymerization. Free dopamine was incorporated into the polycarbonate via nucleophilic substitution of the pendent benzyl chloride (BnCl) groups with the primary amine group of dopamine. The presence of dopamine molecules facilitates the polymers to anchor on the surface. The polymer coating synthesized with the optimal hydrophobic quaternizing agent is able to kill both Gram-positive and Gram-negative bacteria in solution and prevent bacterial fouling on the catheter surface.
The introduction of reversible covalent bonds into polymeric systems afford robust, yet dynamic, materials that can respond to external stimuli. A series of aliphatic polycarbonate polymers were synthesized via ring-opening polymerization of furanyl and maleimido-bearing cyclic carbonate monomers. These side chains undergo thermally induced Diels–Alder reactions to afford cross-linked films. Because both the diene and dienophile were incorporated into the same polymer backbone, a protected maleimido group, in the form of the furan adduct, was used. Both the forward and reverse Diels–Alder reaction are triggered thermally, which allows the deprotection of the maleimido group and the subsequent reaction with the furanyl side chains to form cross-links. Random copolymers and poly(ethylene glycol) containing block copolymers were formed using diazabicyclo[5.4.0]undec-7-ene as the catalyst and a thiourea cocatalyst. The polymers form uniform films that can be cross-linked in the bulk state. To further illustrate the dynamic nature of the covalent bonds within the cross-linked films, a patterned silicon mold was used to transfer a series of nanoscale patterns using a thermal nanoimprint process.
A series of biodegradable polycarbonate polymers was designed and synthesized via organocatalytic ring-opening polymerization of functional cyclic carbonate monomer (MTC–OCH2BnCl). By adopting a facile postpolymerization functionalization strategy, the polycarbonates were quaternized to yield cationic polymers with quaternary ammonium groups of various pendant structures (e.g., alkyl, aromatic, imidazolinium). The biological properties of these polymers were investigated by microbial growth inhibition assays against clinically relevant Gram-positive and Gram-negative bacteria, fungus as well as hemolysis assays using rat red blood cells. A judicious choice in the structure of the cationic appendages elucidated that the amphiphilic balance of the polymers is a pertinent determinant to render substantial antimicrobial potency and low hemolysis, consequently affording the polymer pButyl_20 (degree of polymerization, 20; quaternary ammonium group, N,N-dimethylbutylammonium) as a highly efficacious and nonhemolytic antimicrobial agent with a remarkable selectivity of more than 1026. To ameliorate the selectivity against a wider spectrum of microbes including the difficult-to-kill Pseudomonas aeruginosa, it was shown that polymers containing N,N-dimethylbutylammonium and N,N-dimethylbenzylammonium groups in 1:1 molar ratio exerted considerable antimicrobial potency while remaining relatively nonhemolytic. Biophysical studies encompassing the determination of water-octanol partition coefficients (log P) and dye leakage studies from model liposomes provided useful insights which delineate the pivotal role of cationic group structure in the antimicrobial activity and mechanism of these polymers. Through field emission scanning electron microscopy (FE-SEM), a physical lysis of microbial cell membranes was deemed operative in the antimicrobial action of these macromolecular agents, which would consequently reduce the propensity toward resistance development. These polymers are envisaged to be promising antimicrobial agents for the prevention and treatment of multidrug-resistant pathogenic infections.
This work describes the covalently binding of 2-hydroxyethyl methacrylate (HEMA) and 2-(dimethylamino)ethyl methacrylate(DMAEMA) brushes onto the poly(vinylidene fluoride) (PVDF) membrane surfaces via surface-initiated atom transfer radical polymerization (ATRP). Prior to ATRP, PVDF was coated with 3,4-dihydroxyphenylalanine (DOPA). The hydroxyl groups on the polyDOPA-coated PVDF membrane surface and pore surface were used for the immobilization of alkyl halide ATRP initiator. The grafting yield of poly(hydroxyethyl methacrylate) (PHEMA) and poly((dimethylamino)ethyl methacrylate) (PDMAEMA) was determined by weight gain which was linearly increased with the polymerization time. Fourier transform infrared spectrometer (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscope (AFM) were used to characterize the chemical composition and surface morphology of PVDF membrane and modified membrane, respectively. Water contact angles and water intake measurements indicated that the introduction of PHEMA graft chains promoted remarkably the surface hydrophilicity of PVDF membranes. It was also found that PHEMA graft chains provided higher pure water flux and better anti-protein absorption ability to PVDF membranes. Water flux decreased with increasing polymerization times, while the BSA rejection curves shifted to lower molecular weight cutoff values. The quaternized PVDF-g-PDMAEMA, PVDF-g-PDMAEMA-b-PHEMA membranes exhibited excellent antibacterial properties against Staphylococcus aureus. This study not only introduces a modification approach to obtain a PVDF membrane grafting hydrophilic PHEMA, but also provides the antibacterial properties for PVDF membrane with PDMAEMA.
A series of vitamin E-containing biodegradable antimicrobial cationic polycarbonates is designed and synthesized via controlled organocatalytic ring-opening polymerization. The incorporation of vitamin E significantly enhances antimicrobial activity. These polymers demonstrate broad-spectrum antimicrobial activity against various microbes, e.g., S. aureus (Gram-positive), E-coli (Gram-negative) and C. albicans (fungi). More importantly, the co-delivery of such polymers with selected antibiotics (e.g., doxycycline) shows high synergism towards difficult-to-kill bacteria P. aeruginosa. These findings suggest that these vitamin E-functionalized polycarbonates are potentially useful antimicrobial agents against challenging bacterial/fungal infections.
Purpose: To review the literature on prevention of intravascular catheter-related infections. Data Sources: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. Primary authors were contacted directly if data were incomplete. Study Selection: Studies met the following criteria unless otherwise stated: Trials were prospective and randomized; catheters were inserted into new sites, not into old sites over guidewires; catheter cultures were done by using semi-quantitative or quantitative methods; and, for prospective studies, catheter-related bloodstream infection was confirmed by microbial growth from percutaneously drawn blood cultures that matched catheter cultures. Data Extraction: Data on population, methods, preventive strategy, and outcome (measured as catheter-related bloodstream infections) were gathered. The quality of the data was graded by using preestablished criteria. Data Synthesis: The recommended preventive strategies with the strongest supportive evidence are full barrier precautions during central venous catheter insertion; subcutaneous tunneling short-term catheters inserted in the internal jugular or femoral veins when catheters are not used for drawing blood; contamination shields for pulmonary artery catheters; povidone-iodine ointment applied to insertion sites of hemodialysis catheters; specialized nursing teams caring for patients with short-term peripheral venous catheters, especially at institutions with a high incidence of catheter-related infection; no routine replacement of central venous catheters; antiseptic chamber-filled hub or hub-protective antiseptic sponge for central venous catheters; and use of chlorhexidine-silver sulfadiazine-impregnated or minocycline-rifampin-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies that do not incorporate antimicrobial agents (for example, maximal barrier precautions). Conclusions: Simple interventions can reduce the risk for serious catheter-related infection. Adequately powered randomized trials are needed.
The structural flexibility and efficacy of thiourea−amine catalysts for the supramolecular activation and ring-opening polymerization (ROP) of lactide are described. The nature of the hydrogen bonding group and its strength as well as the steric congestion have been altered, leading to shorter polymerization times, better control, and pathways to influence the stereochemistry of the resulting polymer. The tolerance to functionality and the mild conditions of the ROP mechanism allow for block copolymer synthesis by combination of nitroxide-mediated polymerization as well as reversible addition fragmentation and chain transfer polymerization using dual-headed initiators. Tandem hydrogen bond activation to organocatalyze ROP of lactide is an effective, versatile means to generate polymers with predictable molecular weights, narrow polydispersities, control of microstructure and a variety of complex architectures and block copolymers.
A novel class of antimicrobial cationic polycarbonate/PEG hydrogels are designed and synthesized by Michael addition chemistry. These hydrogels demonstrate strong broad-spectrum antimicrobial activities against various clinically isolated multidrug-resistant microbes. Moreover, they exhibit nonfouling properties and prevent the substrate from microbial adhesion. These antimicrobial and antifouling gels are promising materials as catheter coatings and wound dressings to prevent infections.
This paper examines the hypothesis that surfaces resistant to protein adsorption should also be resistant to the adhesion of bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and the attachment and spreading of mammalian cells (bovine capillary endothelial (BCE) cells). The surfaces tested were those of self-assembled monolayers (SAMs) terminated with derivatives of tri(sarcosine) (Sarc), N-acetylpiperazine, permethylated sorbitol, hexamethylphosphoramide, phosphoryl choline, and an intramolecular zwitterion (-CH2N + (CH3)2CH2CH2CH2SO3 -) (ZW); all are known to resist the adsorption of proteins. There seems to be little or no correlation between the adsorption of protein (fibrinogen and lysozyme) and the adhesion of cells. Surfaces terminated with derivatives of Sarc and N-acetylpiperazine resisted the adhesion of S. aureus and S. epidermidis as well as did surfaces terminated with tri(ethylene glycol). A surface that presented Sarc groups was the only one that resisted the adhesion of BCE cells as well as did a surface terminated with tri(ethylene glycol). The attachment of BCE cells to surfaces could be patterned using SAMs terminated with derivatives of Sarc, N-acetylpiperazine, phosphoramide, and the ZW as the attachment-resistant component and methyl-terminated SAMs as the adhesive component.
Intravascular catheter-associated infections (CAIs), which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, strategies to prevent CAIs are in great demand. In this study, a series of diblock copolymers of PEG and cationic polycarbonate with various compositions were synthesized by metal-free organocatalytic ring-opening polymerization, and coated onto silicone rubber (a commonly used catheter material) at different concentrations via a reactive polydopamine coating. Static contact angle and X-ray photoelectron spectroscopy measurements proved the successful coating, and quartz crystal microbalance results showed that the coating thickness increased as polymer concentration increased. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates - leading causes of intravascular CAIs - were employed to evaluate the antibacterial and antifouling activities of the polymer coatings. Polymer coatings with a hydrophobic component effectively killed planktonic MSSA and MRSA in solution and prevented their fouling on silicone rubber surface. Live/dead cell staining experiments revealed that polymer coatings with the optimal polymer composition possessed significantly higher antifouling activity than PEG coating. In addition, scanning electron microscopic studies showed that the polymer coating inhibited S. aureus biofilm formation over a period of 7 days. Furthermore, the polymer coating caused no significant hemolysis, and there was no blood protein adsorption or platelet adhesion observed. Therefore, PEG-b-cationic polycarbonates with optimal compositions are effective antifouling and antibacterial coatings for the prevention of intravascular CAIs.
Plasma treatment is a useful way of enhancing the wettability of polydimethylsiloxane (PDMS). The subsequent recovery of hydrophobicity in air once treatment is discontinued is well known, but less has been reported about the effect of the storage environment. Water storage is the most relevant, with some reports that this stops the hydrophobic recovery of plasma-treated Medical Grade PDMS elastomer. This is not our experience with a commercial industrial PDMS sealant that had been treated by a helium radio-frequency plasma and stored in pure water and in artificial sea water. Substantial hydrophobic recovery occurs on storage in these environments. The commercial sealant is likely to have more low molecular weight diffusible species and more pre-existing silanol groups than the Medical Grade material. Both of these factors could affect the recovery mechanism by diffusion of untreated polymer chains to the surface or reorientation of polar and non-polar groups in the surface region.
Poly(dimethyl siloxane) (PDMS) is extensively used for biomedical applications due to its low cost, ease of fabrication, high durability and flexibility, oxygen permeability, and self-healing properties. PDMS, however, has some significant drawbacks. PDMS endures unacceptably high levels of nonspecific protein fouling when used with biological samples due to its superhydrophobic characteristics. Unfortunately, conventional surface modification methods do not work for PDMS due to its low glass transition temperature. This phenomenon has been well-known for years as "hydrophobic regeneration". For the same reason, it is also very difficult to bring functionalities onto PDMS surfaces. Herein, we demonstrate how a superhydrophilic zwitterionic material, poly(carboxybetaine methacrylate) (pCBMA), can provide a highly stable coating with long-term stabilty due to the sharp contrast in hydrophobicity between pCBMA and PDMS. This material is able to suppress nonspecific protein adsorption in complex media and functionalize desired biomolecules needed in applications, such as diagnostics, without sacrificing its nonfouling characteristics.
Polyurethane surface was modified with poly(ethylene glycol) (mol. wt. 1000, PEG1k) carrying terminal hydroxyl, amino and sulfonate groups, poly(ethylene glucol) (mol. wt. 3350, PEG3.4k) and PEG3.4k-Heparin, respectively. These surfaces were investigatted for bacterial adhesion using S. epidermidis and E. coli in tryptic soya broth (TSB), brain heart infusion (BHI), and human plasma. All PEG modified surfaces reduced bacterial adhesion significantly and the adhesion level differs depending on surfaces as well as media. In the case of PEG1k surfaces, no reduction of S. epidermidis adhesion was demonstrated in TSB media, regardless of terminal functional groups of PEG1k. However, adhesioin in plasma was reduced to the different degree, depending on terminal groups of PEG1k (least adhesion on sulfonated PEG surface). Relatively longer PEG surface (PEG3.4k) and PEG3.4k-heparin surface minimized bacterial adhesion in both media. In the case of E. coli adhesion, significant reduction in adherent bacteria was observed on all PEG1k, PEG3.4k, and PEG-heparin surfaces in both media compared to controls. In contrast, no reductioin in bacterial adhesion was demonstrated on poly(propylene glycol) (PPG1k) grafted PU surface as compared to control PU. These results suggest that surface modification with PEG1k-SO3, PEG3.4k and PEG3.4k-heparin seems to be effective for prevention of bacterial adhesion and subsequent infection.
Continuous culture is a powerful technique for studying microbial biofilms because it allows for the control of growth rate through nutrient limitation. These conditions offer a realistic view of how microorganisms interact in natural ecosystems. The vast majority of biofilm research is performed with batch cultures, due to the high cost of commercially produced chemostats. We describe a chemostat that could be assembled on a limited budget and could be used in a variety of continuous culture experiments, including biofilm assays. Our design consists of an Erlenmeyer flask with custom-blown ports for aeration and waste removal/direct sampling, and a third port that allows microorganisms in the reaction flask to be circulated through a modified Robbins device and returned via the mouth of the flask. This device enables the formation of highly reproducible biofilm populations, of for example, Aeromonas hydrophila, at various growth rates. As such, it is well-suited for the study of the physiology and genetics of biofilm bacteria.
Osteoclast differentiation is affected by substrate characteristics and environmental conditions; these parameters are therefore of interest for understanding bone remodeling. As a step toward osteoclast mechanotransduction experiments, we aimed to optimize conditions for osteoclast differentiation on extendable poly(dimethylsiloxane) (PDMS) substrates. Because cells attach poorly on PDMS alone, chemical modification by covalent attachment of collagen type I was performed. Effects of collagen surface concentrations on monocyte fusion and osteoclast differentiation were examined. Osteoclasts differentiated on modified PDMS were fewer in number (by ∼50%) than controls on polystyrene physically modified by nonspecific attachment of collagen, and exhibited somewhat different morphologies. Nevertheless, for certain choices of the chemical modification procedures, appropriate differentiation on PDMS was still evident by qRT-PCR analysis for tartrate-resistant acid phosphate (TRAP) and cathepsin K (CTSK) gene expression, positive TRAP staining, fluorescent phalloidin staining showing actin ring formation and bone resorption assays. At relatively high collagen surface densities, monocyte clumps appeared on PDMS suggesting substrate-induced alterations to monocyte fusion. Covalently bound collagen can therefore be used to promote osteoclast differentiation on extendable PDMS substrates. Under appropriate conditions osteoclasts retain similar functionality as on polystyrene, which will enable future studies of osteoclast interactions with microstructured surfaces and mechanostimulation.
Water-soluble, thermoresponsive block copolymers based on a biodegradable platform were synthesized by the ring opening polymerization of cyclic carbonate monomers functionalized with hydrophilic and hydrophobic groups for application as nanocarriers in medicine. The approach based on cyclic carbonate monomers derived from 2,2-bis(methylol)propionic acid (bis-MPA) allowed a simple and versatile route to functional monomers capable of undergoing ring opening polymerization (ROP). The resulting polymers possessed the predicted molecular weights based on the molar ratio between monomers to initiators and the narrow molecular weight distributions. Transmittance measurement for aqueous polymer solutions provided an evidence for temperature-responsiveness with lower critical solution temperature (LCST) in the range of 36 °C-60 °C, depending on the molecular weight of hydrophilic poly(ethylene glycol) (PEG) chains, compositions of copolymers, molar ratios of hydrophilic to hydrophobic monomers in the corona, and the hydrophobic core. This study showed synthetic advancement toward the design and preparation of biodegradable thermoresponsive polymers with extremely low CMC values for injectable drug delivery systems. TRC350-10,30,60, which possessed an LCST of 36 °C in PBS, was identified as a useful model polymer. Paclitaxel, an anti-cancer drug, was loaded into the micelles efficiently, giving rise to nano-sized particles with a narrow size distribution. Paclitaxel release from the micelles was faster, and cellular uptake of the micelles was higher at the body temperature (i.e. 37 °C) as compared to a temperature below the LCST. While the polymer was not cytotoxic, paclitaxel-loaded micelles killed HepG2 human liver carcinoma cells more efficiently at the body temperature as compared to free paclitaxel and paclitaxel-loaded micelles at the temperature below the LCST. These micelles are ideally suited to deliver anti-cancer drugs to tumor tissues through local injection.
Macromolecular antimicrobial agents such as cationic polymers and peptides have recently been under an increased level of scrutiny because they can combat multi-drug-resistant microbes. Most of these polymers are non-biodegradable and are designed to mimic the facially amphiphilic structure of peptides so that they may form a secondary structure on interaction with negatively charged microbial membranes. The resulting secondary structure can insert into and disintegrate the cell membrane after recruiting additional polymer molecules. Here, we report the first biodegradable and in vivo applicable antimicrobial polymer nanoparticles synthesized by metal-free organocatalytic ring-opening polymerization of functional cyclic carbonate. We demonstrate that the nanoparticles disrupt microbial walls/membranes selectively and efficiently, thus inhibiting the growth of Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and fungi, without inducing significant haemolysis over a wide range of concentrations. These biodegradable nanoparticles, which can be synthesized in large quantities and at low cost, are promising as antimicrobial drugs, and can be used to treat various infectious diseases such as MRSA-associated infections, which are often linked with high mortality.
Bacterial adherence to the urinary catheter is an early step in biofilm formation and the pathogenesis of catheter associated urinary tract infection. We studied in vitro the effect of silver or nitrofurazone impregnation of urinary catheters on uropathogen ability to adhere to urinary catheters.
We studied commercially available nitrofurazone-silicone, silicone only, silver-silicone-hydrogel, silicone-hydrogel, silver-latex-hydrogel and latex-hydrogel catheters. Catheters were incubated in sterile broth for 0, 3, 5, 7 and 10 days, respectively, before inoculation and overnight incubation with Escherichia coli or Enterococcus faecalis.
Adherence of E. coli and E. faecalis to nitrofurazone catheters was significantly decreased compared to that of silicone-only catheters when catheters were fresh. The anti-adherence effect of nitrofurazone on E. coli decreased with time but was still significant at 5 days. For E. faecalis the effect of nitrofurazone was lost by 3 days of pre-incubation. E. coli adherence was not significantly decreased on silver impregnated catheters compared to that on control catheters of the same base material. Silver was associated with a significant decrease in E. faecalis adherence to latex-hydrogel catheters but not to silicone-hydrogel catheters. The adherence of each species to silicone catheters with hydrogel was significantly lower than that to silicone-only control catheters.
Silver impregnation had little effect on bacterial adherence in our model and nitrofurazone impregnation had a significant effect only for the first 5 days. Our results do not support a role for silver urinary catheters to prevent catheter associated urinary tract infection by decreasing bacterial adherence.
The major strategies for designing surfaces that prevent fouling due to proteins, bacteria, and marine organisms are reviewed. Biofouling is of great concern in numerous applications ranging from biosensors to biomedical implants and devices, and from food packaging to industrial and marine equipment. The two major approaches to combat surface fouling are based on either preventing biofoulants from attaching or degrading them. One of the key strategies for imparting adhesion resistance involves the functionalization of surfaces with poly(ethylene glycol) (PEG) or oligo(ethylene glycol). Several alternatives to PEG-based coatings have also been designed over the past decade. While protein-resistant coatings may also resist bacterial attachment and subsequent biofilm formation, in order to overcome the fouling-mediated risk of bacterial infection it is highly desirable to design coatings that are bactericidal. Traditional techniques involve the design of coatings that release biocidal agents, including antibiotics, quaternary ammonium salts (QAS), and silver, into the surrounding aqueous environment. However, the emergence of antibiotic- and silver-resistant pathogenic strains has necessitated the development of alternative strategies. Therefore, other techniques based on the use of polycations, enzymes, nanomaterials, and photoactive agents are being investigated. With regard to marine antifouling coatings, restrictions on the use of biocide-releasing coatings have made the generation of nontoxic antifouling surfaces more important. While considerable progress has been made in the design of antifouling coatings, ongoing research in this area should result in the development of even better antifouling materials in the future.
Ring-opening polymerization (ROP) of functionalized cyclic carbonates derived from 2,2-bis(methylol)propionic acid (bis-MPA) allows for incorporation of H-bonding urea-functional groups into block copolymers with a potential application of supramolecular drug-delivery systems. The strong H-bonding functionalities of poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E(1-x)-U(x))C) block copolymers not only lowered critical micelles concentration (cmc) of the block copolymer (to 1/4x) in aqueous environment compared to conventional PEG-poly(trimethylene carbonate) (PEG-PTMC) block copolymer without the non-covalent stabilization, but also improved kinetic stability of micelles and Dox-loaded micelles in the presence of a destabilizing agent. It was observed that the incorporation of anticancer drug doxorubicin affected the micellization process of block copolymers in water and caused a sudden increase in sizes of drug-loaded micelles above 200 nm. This phenomenon that can be a significant drawback in drug delivery applications was considerably mitigated in urea-bearing block copolymer/Dox micelles with simultaneously accompanying a significant improvement in drug loading. In vitro drug release profile showed that the increase in urea content led to a slight decrease in Dox release rate. Block copolymer did not have any significant cytotoxicity against HEK293 and HepG2 cells up to 400 mg/L. Importantly, Dox-loaded micelles exerted cytotoxic effect against HepG2 cells.
Ureteral stents find wide application in urology. The majority of patients with indwelling ureteral stents are at an increased risk of urinary tract infection. Stent encrustation and its associated complications lead to significant morbidity. This review critically evaluates various polymers that find their application as ureteral stents with regard to various issues such as encrustation, bacterial colonization, urinary tract infections, and related clinical issues. A complete literature survey was performed, and all the relevant articles were scrutinized thoroughly. We discuss issues of encrustation/biofilm formation, new approaches to their testing, polymers currently available for use, new biomaterials, coatings, and novel ureteral stent designs, thereby providing a complete update on recent advances in the development of stents. Finally, we discuss the future of biomaterial use in the urinary tract.