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Eugenol is a phenolic monoterpenoid, emplyed in this study to obtain bio-based antimicrobial and antioxidant methacrylate polymers.

This study combines the use of corn starch and Tetradesmus obliquus microalgae for the production of antioxidant starch films as flexible packaging material. Starch was plasticized with glycerol and blended with 1 w% polyallylamine chosen as an agent to modify the film physical properties. The addition of polyallylamine improved film water stability and water vapor transmission rate as well as mechanical stiffness and tenacity. The dried Tetradesmus obliquus microalgae, which showed an EC50 value of 2.8 mg/mg DPPH (2.2-Diphenyl-1-picrylhydrazyl radical), was then used as antioxidant filler. The addition of microalgae provided the films with good antioxidant activity, which increased with microalgae content increasing. To our knowledge, this is the first study reporting the development of sustainable bioactive packaging films composed of almost 100% starch, and follows the European union’s goals on plastics strategy concerning the promotion of bio-based, compostable plastics and the setting up of approaches to prevent food waste with a simple plastic packaging.

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved.

The development of low-cost and eco-friendly materials for the removal of pollutants from water is one of the main modern challenges. For this purpose, molecularly imprinted polymers were prepared under optimized conditions starting from chitosan (CS), chemically or ionically modified with glycidyl methacrylate (GMA) or itaconic acid (ITA), respectively. 2,4-Dichlorophenoxyacetic acid (2,4-D) was used as a template, obtaining the CS_GMA and CS_ITA series. The influence of the template concentration on the MIPs’ (molecularly imprinted polymers) morphology, thermal behaviour and swelling ability, as well as on the 2,4-D removal capacity, were analyzed. The amount of the template used for the imprinting, together with the different permeability of the matrices, were the key factors driving the analyte uptake process. Despite the good performance shown by the non-imprinted CS_GMA sample, the best results were obtained when CS_GMA was imprinted with the highest amount (5%) of template (CS_GMA_5). This system was also more efficient when consecutive adsorption experiments were carried out. In addition, CS_GMA_5 had a desorption efficiency of 90–100% when a low pesticide concentration was used. These findings suggest that the presence of imprinted cavities could be useful in improving the performance of sorbent materials making CS_GMA_5 a possible candidate for 2,4-D removal., This research was funded by the Sapienza University of Rome, through a grant to A.P. (RM11916B6F8A0DF6).

This article focuses on the study related to the estimation of packaging material properties of cellulose–wax nanocomposite using molecular dynamics simulation (MDS). Cellulose based packaging material is gaining lot of importance due to its good material properties and low cost. Cellulose with small amount of plant-derived wax (nonacosane-10-ol and nonacosane-5,10-diol) offers higher mechanical strength and modulus of elasticity compared to the conventional synthetic polymer materials. In this article, in addition to the estimation of mechanical properties, the thermal stability of the proposed ecofriendly cellulose–wax composite is evaluated by estimating the glass transition temperature which essentially provides critical information on the glassy state and rubbery state of this biopolymer. The glass transition temperature of this composite changes significantly compared to that of pure cellulose (which also suffers from poor mechanical strength). Transport properties such as diffusion volume and diffusion coefficient of oxygen, nitrogen, and water are estimated using the results obtained from MDS. The diffusion coefficients of these species within the cellulose–wax composite are analyzed using the diffusion volume and interaction energies of these constituents with the wax and cellulose.

In this paper, the application of a temperature modulation to the temperature-resolved FTIR analysis is reported. The advantage offered by the spectroscopic investigation, able to follow the micro-structural and conformational sample modification involved in sample thermal transformation, was merged to that of temperature modulation, related to the possibility to separate the reversing (in-equilibrium within the experimental condition) to the non-reversing (non-equilibrium) processes. The potentiality of the technique (modulated temperature FTIR, MTFTIR) is highlighted through the study of the thermal transitions of amorphous poly(ethylene terephthalate) from 50 °C to the cold-crystallization. After the presentation of the theoretical framework and the experimental conditions, a step-by-step description of acquired data elaboration is given. The total variation of a selected band intensity as function of mean temperature as well as its reversing and non-reversing components are obtained. The evolution of the bands at 1340 and 971 cm−1, assigned to the trans conformation of the ethylenic unit and to the all-trans conformation of the repeating unit, respectively, are investigated. As expected, the glass transition is observed in the reversing components meanwhile the recovery of the glass relaxation and cold crystallization in non-reversing ones. Particularly interesting resulted the behaviour of the sample in the supercooled liquid state, between the glass transition and the cold-crystallization onset, in which the results show that the ethylenic conformers are in-equilibrium while the all-trans sequences are not. MTFTIR is confirmed to be a technique particularly suitable for the characterization of non-equilibrium conformational states of polymers.

Solid-phase extraction (SPE) coupled to LC/MS/MS analysis is a valid approach for the determination of organic micropollutants (OMPs) in liquid samples. To remove the greatest number of OMPs from environmental matrices, the development of innovative sorbent materials is crucial. Recently, much attention has been paid to inorganic nanosystems such as graphite-derived materials. Graphene oxide has been employed in water-purification processes, including the removal of several micropollutants such as dyes, flame retardants, or pharmaceutical products. Polysaccharides have also been widely used as convenient media for the dispersion of sorbent materials, thanks to their unique properties such as biodegradability, biocompatibility, nontoxicity, and low cost. In this work, chitosan–graphene oxide (CS_GO) composite membranes containing different amounts of GO were prepared and used as sorbents for the SPE of pesticides. To improve their dimensional stability in aqueous medium, the CS_GO membranes were surface crosslinked with glutaraldehyde. The composite systems were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, swelling degree, contact angle, and mechanical measurements. As the GO content increased, a decrease in surface homogeneity, an improvement of mechanical properties, and a reduction of thermal stability of the CS-based membranes were observed. The increased dimensional stability in water, together with the presence of high GO amounts, made the prepared composite membranes more efficacious than the ones based just on CS in isolating and preconcentrating different hydrophilic/hydrophobic pollutants.

In this study, a new scaffold fabrication method based on the combination of a series of stabilization processes was set up to obtain chitosan scaffolds with improved mechanical properties for regeneration of load-bearing tissues. Specifically, thermally induced phase separation (TIPS) of chitosan solutions was used to obtain an open structure which was then stabilized by freeze-gelation and photo cross-linking. Freeze-gelation combined with freeze-drying permitted to obtain a porous structure with a 95 μm-mean pore size suitable for osteoblast cells' housing. Photo-crosslinking improved by ca. three times the scaffold compressive modulus, passing from 0,8 MPa of the uncrosslinked scaffolds to 2,2 MPa of the crosslinked one. Hydrated crosslinked scaffolds showed a good elastic response, with an 80% elastic recovery for at least 5 consecutive compressive cycles. The herein reported method has the advantage to not require the use of potentially toxic cross-linking agents and may be extended to other soft materials.

Chitosan is very effective in removing metal ions through their adsorption. A preliminary investigation of the adsorption of chromium(III) by chitosan was carried out by means of batch tests as a function of contact time, pH, ion competition, and initial chromium(III) concentration. The rate of adsorption was rather rapid (t1/2 &lt, 18 min) and influenced by the presence of other metal ions. The obtained data were tested using the Langmuir and Freundlich isotherm models and, based on R2 values, the former appeared better applicable than the latter. Chitosan was found to have an excellent loading capacity for chromium(III), namely 138.0 mg Cr per g of chitosan at pH = 3.8, but metal ions adsorption was strongly influenced by the pH. About 76% of the recovered chromium was then removed simply by washing the used chitosan with 0.1 M EDTA (Ethylenediaminetetraacetic acid) solution. This study demonstrates that chitosan has the potential to become an effective and low-cost agent for wastewater treatment (e.g., tannery waste) and in situ environmental remediation.

Background: Antioxidants are multifaceted molecules playing a crucial role in several cellular functions. There is by now a well-established knowledge about their involvement in numerous processes associated with aging, including vascular damage, neurodegenerative diseases and cancer. An emerging area of application has been lately identified for these compounds in relation to the recent findings indicating their ability to affect biofilm formation by some microbial pathogens, including Staphylococcus aureus, Streptococcus mutans, and Pseudomonas aeruginosa. Methods: A structured search of bibliographic databases for peer-reviewed research literature was performed using a focused review question. The quality of retrieved papers was appraised using standard tools. Results: One hundred sixty-five papers extracted from pubmed database and published in the last fifteen years were included in this review focused on the assessment of the antimicrobial and antibiofilm activity of antioxidant compounds, including vitamins, flavonoids, non-flavonoid polyphenols, and antioxidant polymers. Mechanisms of action of some important antioxidant compounds, especially for vitamin C and phenolic acids, were identified. Conclusion: The findings of this review confirm the potential benefits of the use of natural antioxidants as antimicrobial/antibiofilm compounds. Generally, gram-positive bacteria were found to be more sensitive to antioxidants than gram-negatives. Antioxidant polymeric systems have also been developed mainly derived from functionalization of polysaccharides with antioxidant molecules. The application of such systems in clinics may permit to overcome some issues related to the systemic delivery of antioxidants, such as poor absorption, loss of bioactivity, and limited half-life. However, investigations focused on the study of antibiofilm activity of antioxidant polymers are still very limited in number and therefore they are strongly encouraged in order to lay the foundations for application of antioxidant polymers in treatment of biofilm-based infections.

Wound healing is a dynamic process that can be seriously delayed by many factors including infectious complications. The development of dressings with intrinsic wound healing activity and/or releasing bioactive compounds may help with addressing such an issue. In this study, hyaluronic acid (HA) at different percentages (1&ndash, 35%) was used to modify chitosan (CS) biological and physico-chemical properties in order to obtain 2D-matrices able to promote healing and protect from infection. HA incorporation in the CS matrix decreased film transparency and homogeneity, but improved film water uptake and surface wettability. The water vapor transmission rate (WVTR) increased up to a 5% HA content, where it reached the highest value (672 g/m2 day), and decreased for higher HA contents. At all of the tested HA concentrations, HA affected mechanical properties providing matrices more flexible than pure CS with benefit for wound care. Pure CS films permitted S. epidermidis adhesion and biofilm formation. That was not true for CS/HA matrices, where HA at concentrations equal to or greater than 5% was able to avoid S. epidermidis adhesion. Fibroblasts adhesion also took benefit from the HA presence in the film, especially at 5% content, where the best adhesion and proliferation was found.

The aim of this work was to prepare and characterize solid dispersions of abietic acid (AB) and chitosan (CS) to investigate how formulation of the mixture may help in the battle against microbial colonization in different areas, such as the biomedical field or the food industry. Solid dispersions were characterized by differential scanning calorimetry, infrared spectroscopy, Raman spectroscopy, polarized optical microscopy, zeta potential and size analysis. The data showed that the dispersion/solvent evaporation method formed solid dispersions in which abietic acid was molecularly dispersed in the carrier. A synergistic effect between the two components in terms of antioxidant and antimicrobial properties was found, especially in the formulations obtained with 1/1 AB/CS molar ratio. Interestingly, the aggregation state (amorphous/crystalline) of AB seemed to affect the antimicrobial activity of the formulation, suggesting increased bioactivity when the drug was in the amorphous state. These findings, together with the demonstrated biocompatibility of the formulations, seem to open promising perspectives for a successful application of the developed AB/CS formulations in the biomedical field or in the food industry.

Lipase-immobilized nanomaterials with high activity and stable reusability would have a great impact in different fields. However, developing such materials has proven to be challenging. Herein, polymer (pAcDED)-coated magnetic nanoparticles (MNPs) displaying long alkyl chains, either octyl (C8) or hexadecyl (C16), have been prepared and used for immobilization of Candida rugosa lipase. The aim of the study was to develop magnetic supports able to bind enzyme via interfacial activation thus to stabilized the lipase open conformation. Among the developed nanosupports, the one endowed with the longest alkyl chains (MNPs-pAcDED-C16) provided the best efficiencies of the immobilized enzyme (70% vs. tributyrin and 130% vs. ethyl butyrate). Such results suggest both enzyme adsorption in open conformation and a change of enzyme specificity during immobilization. The MNPs-pAcDED-C16 system also showed better resistance to temperature inactivation in the 25–70 °C temperature range compared to free lipase and good reusability (4 consecutive cycles). The overall performances together with the convenience in the recovery offered by magnetic separation indicate our surface-modified MNPs as efficient and environmentally compatible materials for lipase immobilization.

Tissue engineering is a highly interdisciplinary field of medicine aiming at regenerating damaged tissues by combining cells with porous scaffolds materials. Scaffolds are templates for tissue regeneration and should ensure suitable cell adhesion and mechanical stability throughout the application period. Chitosan (CS) is a biocompatible polymer highly investigated for scaffold preparation but suffers from poor mechanical strength. In this study, graphene oxide (GO) was conjugated to chitosan at two weight ratios 0.3% and 1%, and the resulting conjugates were used to prepare composite scaffolds with improved mechanical strength. To study the effect of GO oxidation degree on scaffold mechanical and biological properties, GO samples at two different oxygen contents were employed. The obtained GO/CS scaffolds were highly porous and showed good swelling in water, though to a lesser extent than pure CS scaffold. In contrast, GO increased scaffold thermal stability and mechanical strength with respect to pure CS, especially when the GO at low oxygen content was used. The scaffold in vitro cytocompatibility using human primary dermal fibroblasts was also affected by the type of used GO. Specifically, the GO with less content of oxygen provided the scaffold with the best biocompatibility.

Despite advances in material sciences and clinical procedures for surgical hygiene, medical device implantation still exposes patients to the risk of developing local or systemic infections. The development of efficacious antimicrobial/antifouling materials may help with addressing such an issue. In this framework, polyethylene glycol (PEG)-grafted segmented polyurethanes were synthesized, physico-chemically characterized, and evaluated with respect to their bacterial fouling-resistance properties. PEG grafting significantly altered the polymer bulk and surface properties. Specifically, the PEG-grafted polyurethanes possessed a more pronounced hard/soft phase segregated microstructure, which contributed to improving the mechanical resistance of the polymers. The better flexibility of the soft phase in the PEG-functionalized polyurethanes compared to the pristine polyurethane (PU) was presumably also responsible for the higher ability of the polymer to uptake water. Additionally, dynamic contact angle measurements evidenced phenomena of surface reorganization of the PEG-functionalized polyurethanes, presumably involving the exposition of the polar PEG chains towards water. As a consequence, Staphylococcus epidermidis initial adhesion onto the surface of the PEG-functionalized PU was essentially inhibited. That was not true for the pristine PU. Biofilm formation was also strongly reduced.

Usnic acid (UA) is a secondary lichen metabolite extensively studied for the broad variety of biological features. The most interesting property of UA is its antimicrobial activity against Gram-positive bacteria growing either in planktonic or in biofilm mode. In this chapter, the most relevant studies assessing usnic acid activity against microbial biofilms have been summarized and the potential role of UA in the management of biofilm-based wound infections has been critically discussed. Additionally, an overview of the main strategies adopted so far to reduce drug toxicity and increase bioavailability is given in the perspective of a safe use of UA in the clinical management of infected wounds.

The rapid increase in the emergence of antibiotic-resistant bacterial strains combined with a dwindling rate of discovery of novel antibiotic molecules has lately created an alarming issue worldwide [...]

Because of the increased incidence of infections caused by resistant pathogens, due to the intensive use of antibiotics, there is an urgent need to develop new therapeutic strategies against bacteria, possibly based on non conventional drugs. (+)-Usnic acid is a natural compound that exerts a potent antibacterial activity, however its clinical application is hampered by its scarce solubility in water. Usnic acid was included, by both passive and active loading techniques, in liposomes containing structurally related glucosylated amphiphiles. Liposome formulations were characterized from the physicochemical point of view and their activity against biofilm associated Staphylococcus epidermidis was also evaluated. The inclusion of usnic acid in glucosylated cationic liposomes promotes its penetration in biofilm matrix with a consequent increase of its antimicrobial activity. The effect of both cationic charge and sugar residue seems to be synergistic.

Liposomes functionalized on their surface with carbohydrates (glycoliposomes) represent an optimal approach for targeting of drugs to diseased tissues in vivo, thanks to biocompatibility, low toxicity and easy manufacturing of these lipid nanoparticles. Here we report on the study of liposomes including a novel glycosylated amphiphile and on the comparison of their features with those of glycosylated analogues described previously. Further, the capability of the different glucosylated formulations to interact with three breast cancer cell lines was investigated. Our results show that the hydrophobic portion of the lipid bilayer strongly influences both the properties and the internalization of glycosylated liposomes.

The inclusion of pH-sensitive components in liposome formulations can allow a more controlled and efficient release in response to low pH typical of some pathological tissues and/or subcellular compartments. On the other hand decorating the surface of liposomes with sugar moieties attributes to lipid vesicles specificity toward lectins, sugar-binding proteins overexpressed in many tumor tissues. A novel multifunctional pH-sensitive glucosylated amphiphile was synthesized and characterized as pure aggregate component and in mixtures with a natural phospholipid. The comparison of the properties of the new glucosylated amphiphile with respect to those of a previously described cationic structural analogue demonstrates that the pH-sensitivity can strongly affect drug release, lipid organization, as well as the exposure of the glucose residues on liposome surface and their ability to interact with Concanavalin A, a plant lectin used as model system.

A novel hydroxytyrosol-based polyacrylate polymer material (pAcHTy) endowed with metal ion adsorption ability was obtained by free radical polymerization of a monomer containing a hydroxytyrosol precursor (tyrosol). Hydroxytyrosol (HTy) is the main natural polyphenolic compound with antioxidant activity occurring in virgin olive oil and in olive oil wastewaters. pAcHTy showed a good chelating activity with respect to Cu2+ ions, especially at pH 6 where short equilibrium times and high adsorption capacity were observed (146 mg/g). From thermodynamic parameters, it has been found that the sorption process was spontaneous at low temperature and exothermic in nature. The adsorption process has been studied by employing three simplified kinetic models, including a pseudo-first-order equation, pseudo-second-order equation, and intraparticle diffusion equation. Kinetic parameters, rate constants, equilibrium sorption capacities, and related correlation coefficients, for each kinetic model, were calculated and discussed. It was shown that the adsorption of Cu2+ ions could be described by the pseudo-second-order equation, suggesting that the adsorption process is presumable a chemisorption. The pAcHTy polymer could find an important application in the medical field, particularly in chelation therapy as well as in the wastewater and drinking water treatment plants.

Scaffolds are three-dimensional porous structures that must have specific requirements to be applied in tissue engineering. Therefore, the study of factors affecting scaffold performance is of great importance. In this work, the optimal conditions for cross-linking preformed chitosan (CS) scaffolds by the tripolyphosphate polyanion (TPP) were investigated. The effect on scaffold physico-chemical properties of different concentrations of chitosan (1 and 2% w/v) and tripolyphosphate (1 and 2% w/v) as well as of cross-linking reaction times (2, 4, or 8 h) were studied. It was evidenced that a low CS concentration favored the formation of three-dimensional porous structures with a good pore interconnection while the use of more severe conditions in the cross-linking reaction (high TPP concentration and crosslinking reaction time) led to scaffolds with a suitable pore homogeneity, thermal stability, swelling behavior, and mechanical properties, but having a low pore interconnectivity. Preliminary biocompatibility tests showed a good osteoblasts&rsquo, viability when cultured on the scaffold obtained by CS 1%, TPP 1%, and an 8-h crosslinking time. These findings suggest how modulation of scaffold cross-linking conditions may permit to obtain chitosan scaffold with properly tuned morphological, mechanical and biological properties for application in the tissue regeneration field.

Usnic acid (UA) is a secondary lichen metabolite extensively studied for the broad variety of biological features. The most interesting property of UA is its antimicrobial activity against Gram-positive bacteria growing either in planktonic or in biofilm mode. In this chapter, the most relevant studies assessing usnic acid activity against microbial biofilms have been summarized and the potential role of UA in the management of biofilm-based wound infections has been critically discussed. Additionally, an overview of the main strategies adopted so far to reduce drug toxicity and increase bioavailability is given in the perspective of a safe use of UA in the clinical management of infected wounds.

Protein mussel-inspired adhesive polymers, characterized by the presence of catechol groups, possess superior muco-adhesive properties and have great potentiality in wound healing. Suitable materials for wound dressing should properly combine muco-adhesiveness and antimicrobial activity. In this work, catechol-functionalized chitosan was obtained by reaction with hydrocaffeic acid (HCAF), in order to investigate how catechol introduction at different content could affect the intrinsic antimicrobial activity of the polymer itself. Unexpectedly, an enhancement of chitosan antimicrobial activity was observed after catechol functionalization, with a fourfold reduction in the polymer minimum inhibitory concentration versus Staphylococcus epidermidis. Additionally, a commercial wound dressing coated with one of the synthesized CS-HCAF derivatives showed a significant reduction in the adhesion of S. epidermidis compared to the uncoated dressing (3-log reduction). The CS-HCAF derivatives also showed an interesting antioxidant property (EC50 ranging from 20 to 60 μg/mL), which further confirms the potentiality of these materials as wound dressings. © 2017 Elsevier Ltd

Microbial biofilms are known to support a number of human infections, including those related to medical devices. This work is focused on the development of novel dual-function amphiphilic random copolymers to be employed as coatings for medical devices. Particularly, copolymers were obtained by polymerization of an antimicrobial cationic monomer (bearing tertiary amine) and an antioxidant and antimicrobial hydrophobic monomer (containing hydroxytyrosol, HTy). To obtain copolymers with various amphiphilic balance, different molar ratios of the two monomers were used. 1H NMR and DSC analyses evidenced that HTy aromatic rings are able to interact with each other leading to a supra-macromolecular re-arrangement and decrease the copolymer size in water. All copolymers showed good antioxidant activity and Fe2+ chelating ability. Cytotoxicity and hemolytic tests evidenced that the amphiphilic balance, cationic charge density and polymer size in solution are key determinants for polymer biocompatibility. As for the antimicrobial properties, the lowest minimal inhibitory concentration (MIC = 40 μg/mL) against Staphylococcus epidermidis was shown by the water-soluble copolymer having the highest HTy molar content (0.3). This copolymer layered onto catheter surfaces was also able to prevent staphylococcal adhesion. This approach permits not only prevention of biofilm infections but also reduction of the risk of emergence of drug-resistant bacteria. Indeed, the combination of two active compounds in the same polymer can provide a synergistic action against biofilms and suppress reactive species oxygen (ROS), known to promote the occurrence of antibiotic resistance. © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The application of magnetic nanoparticles (MNPs) in medicine is considered much promising especially because they can be handled and directed to specific body sites by external magnetic fields. MNPs have been investigated in magnetic resonance imaging, hyperthermia and drug targeting. In this study, properly functionalized core/shell MNPs with antimicrobial properties were developed to be used for the prevention and treatment of medical device-related infections. Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro-emulsion method, were coated with two different polymers and loaded with usnic acid (UA), a dibenzofuran natural extract possessing antimicrobial activity. Between the two polymer coatings, the one based on an intrinsically antimicrobial cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper magnetic properties and basic groups for UA loading. Thanks to the establishment of acid-base interactions, pAcDED-coated MNPs were able to load and release significant drug amounts resulting in good antimicrobial properties versus Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic antimicrobial activity as MNP coating in combination with UA likely contributed to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could be injected in the patient soon after device implantation to prevent biofilm formation, or, later, in presence of signs of infection to treat the biofilm grown on the device surfaces.

Biocompatible and degradable poly(α-hydroxy acids) are one of the most widely used materials in scaffolds for tissue engineering. Nevertheless, they often need surface modification to improve interaction with cells. Aminolysis is a common method to increase the polymer hydrophilicity and to introduce surface functional groups, able to covalently link or absorb, through electrostatic interaction, bioactive molecules or macromolecules. For this purpose, multi-functional amines, such as diethylenediamine or hexamethylenediamine are used. However, common drawbacks are their toxicity and the introduction of positive charges on the surface. Thus, these kind of modified surfaces are unable to link directly proteins, such as collagens, a promising substrate for many cell types, in particular chondrocytes and osteoblasts. In this work, poly(L-lactide) (PLLA) film surface was labelled with negatively charged sulfonate groups by grafting taurine (TAU) through an aminolysis reaction. The novel modified PLLA film (PLLA-TAU) was able to interact directly with collagen. The reaction was carried out in mild conditions by using a solution of tetrabutylammonium salt of TAU in methanol. ATR-FTIR, XPS and contact angle measurements were used to verify the outcome of the reaction. After the exchange of tetrabutylamonium cation with Na+, collagen was absorbed on the TAU grafted PLLA film (PLLA-TAU-COLL). In vitro biological tests with human primary chondrocytes showed that PLLA-TAU and PLLA-TAU-COLL improved cell viability and adhesion, compared to the unmodified polymer, suggesting that these modifications make PLLA substrate suitable for cartilage repair.

Poly(ethylene glycol) (PEG) stabilized liposomes are widely used in drug delivery research because these surface grafted polymers stabilize liposomes in blood stream. However, hydrophilic polymers also affect lipid membrane organization and it is fundamental to investigate their effect on the physicochemical properties of lipid bilayers as well as on their interaction with biological membrane. PEG monolaurate was included in liposomes formulated with dimyristoyl-sn-glycero-3-phosphocholine and one of two cationic gemini surfactants that differ each other for the configuration of a stereogenic center on the polar headgroup. These formulations previously showed good efficiency as drug and DNA delivery systems. The effect of the presence of different amounts of a PEG-lipid and of the liposome preparation protocol was investigated by turbidimetry, dynamic laser light scattering, differential scanning calorimetry and electrophoretic mobility. Flow cytometry and laser scanning confocal microscopy on murine (C6) and on human glioblastoma (LN229) cell lines were also carried out to evaluate the influence of pegylation and of the protocol of preparation on the interaction of liposomes with the biological milieu.

Buckypaper (BP) is the general definition of a macroscopic assembly of entangled carbon nanotubes. In this paper, a new property of a BP film produced from oxidized multiwalled carbon nanotubes was investigated. In particular, BP shows to be able to promptly and strongly adhere to animal internal soft and wet tissues, as evaluated by peeling and shear tests. BP adhesion strength is higher than that recorded for a commercial prosthetic fabric (sealed to the tissue by fibrin glue) and comparable with that of other reported optimized nanopatterned surfaces. In order to give an interpretation of the observed behavior, the BP composition, morphology, porosity, water wettability, and mechanical properties were analyzed by AFM, X-ray photoelectron spectroscopy, wicking tests, contact angle, and stress-strain measurements. Although further investigations are needed to assess the biocompatibility and safety of the BP film used in this work, the obtained results pave the way for a possible future use of buckypaper as adhesive tape in abdominal prosthetic surgery. This would allow the substitution of conventional sealants or the reduction in the use of perforating fixation.

The use of implantable medical devices is a common and indispensable part of medical care for both diagnostic and therapeutic purposes. However, as side effect, the implant of medical devices quite often leads to the occurrence of difficult-to-treat infections, as a consequence of the colonization of their abiotic surfaces by biofilm-growing microorganisms increasingly resistant to antimicrobial therapies. A promising strategy to combat device-related infections is based on anti-infective biomaterials that either repel microbes, so they cannot attach to the device surfaces, or kill them in the surrounding areas. In general, such biomaterials are characterized by antifouling coatings, exhibiting low adhesion or even repellent properties towards microorganisms, or antimicrobial coatings, able to kill microbes approaching the surface. In this light, the present overview will address the development in the last two decades of antifouling and antimicrobial biomaterials designed to potentially limit the initial stages of microbial adhesion, as well as the microbial growth and biofilm formation on medical device surfaces.

The accumulation of reactive oxygen species (ROS) in microbial biofilms has been recently recognized to play a role in promoting antibiotic resistance in biofilm-growing bacteria. ROS are also over-produced when a medical device is implanted and they can promote device susceptibility to infection or aseptic loosening. High levels of ROS seem also to be responsible for the establishment of chronic wounds.

Intravascular devices are indispensable tools for clinicians. However, complications are still associated with their use, the most common of which is the onset of infections. These infections are usually resistant to antibiotic chemotherapy since they are supported by microbial biofilms. The application of antimicrobial and antifouling polyurethanes (PUs) to intravascular devices represents a valid strategy for reducing the development of device-related infections. Antifouling PUs repel microorganisms approaching the device while antimicrobial polymers are expected to kill microbes either floating in proximity of the device or adhering to the device. Antimicrobial PUs can either release antimicrobials or be intrinsically active. While many antimicrobial agent-releasing PUs have been evaluated in clinics, intrinsically antimicrobial PUs have been mainly studied in vitro . In this chapter, antimicrobial PUs are reviewed and discussed.

The aim of the present work was to study the possibility of building a porous scaffold for tissue engineering with a new bottom-up approach, obtained by assembling two-dimensional-micro, one-dimensional-nano sized poly(L-lactide) lamellar single crystals. This choice was dictated by the fact that polymer single crystals have structural and morphological features which can be exploited for chemical surface modifications to give a system characterized by a high specific active surface area. Indeed, the outermost amorphous regions can undergo functionalization reactions easily, whereas the inner, relatively inaccessible and inert crystalline core ensures morphological and mechanical stability. The assembling method employed to give the porous structures is based on a mould pressing, salt leaching technique and was found to be facile and versatile. In the first part of this paper we report the experimental results obtained to find the best conditions to achieve a suitable frame in terms of morphology, porosity and mechanical properties. In the second part of the paper, we describe the biological tests performed by using mouse fibroblasts seeded onto scaffolds prepared from pristine and surface hydrolysed lamellae. The results show that the samples obtained are suitable for sustaining cells which can proliferate and reach the inner pores of the scaffold containing hydrolysed single crystals much better than those prepared from pristine lamellae. Copyright © 2012 Society of Chemical Industry

The effect of the holding temperature and time in the melt state of poly(L-lactide) (PLLA) samples on the nonisothermal melt crystallization process and on the structure have been investigated by means of DSC, polarized optical microscopy and wide angle X-ray scattering. As standard starting material, single crystals grown from dilute solution were used. In the mild melting condition, the survived athermal nuclei favor high temperature polymer crystallization, while the more severe treatment leads the PLLA to crystallize at higher supercooling with a sporadic nucleation. At the intermediate melting temperature a distinct double nucleation mechanism was observed while at the lower nuclei concentration, a double crystallization rate was also found. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

In recent years the employment of implantable medical devices has increased remarkably, notwithstanding that microbial infections are a frequent complication associated with their use. Different strategies have been attempted to overcome this problem, including the incorporation of antimicrobial agents into the device itself. In this study a new approach to obtain intrinsically antimicrobial materials was developed. Polymer anionomers containing Ag(I), Cu(II), Zn(II), Al(III) and Fe(III) were prepared by neutralization of a carboxylated polyurethane. In the case of the PEUA-Ag, PEUA-Fe and PEUA-Cu ionomers the ion aggregates behaved as reinforcing filler particles, increasing the mechanical properties of the systems in terms of hardness and strength at break over the pristine carboxylated polymer. With the exception of the Al-containing polymer, all the other experimented ionomers showed satisfactory antimicrobial properties. The best antibacterial effect was obtained with the silver ion-containing polymer, which inhibited Staphylococcus epidermidis growth for up to 16 days. Ciprofloxacin was also adsorbed onto the above mentioned ionomers. A synergistic effect of the antibiotic and silver ions on bacterial growth inhibition was observed for at least 25 days.

BACKGROUND: Micellar systems are widely applied as reactors to encapsulate inorganic nanoparticles in polymeric materials. However, only low inorganic contents and microscale dimensions are often achieved. RESULTS: The adsorption of albumin protein on ferrite nanoparticles permits to increase the stability of inorganic dispersions in water by inhibiting particle flocculation. Subsequent glutaraldehyde addition induces protein crosslinking and ferrite entrapment. Polymer–ferrite composite nanoparticles were obtained in this way. The magnetic albumin nanoparticles (25 nm mean diameter) obtained contain about 40 wt% of ferrite and show superparamagnetic behaviour. The composite powder was successfully functionalized with a model drug and the biological activity was evaluated. CONCLUSION: Using a reverse micelle approach, ferrite–albumin composite nanoparticles with a high inorganic content were obtained. The method permits the formulation of biocompatible magnetic particles of nanoscale dimensions. The exhibited superparamagnetic behaviour permits to hypothesize an application of the powder composite as a carrier in biomedical technologies. Copyright © 2009 Society of Chemical Industry

Heparin–Toluidine Blue (C.I. Basic Blue 17) interaction was studied using UV–vis spectroscopic analysis of the titration of the functional groups present on the polyanion chain. The study took into consideration both the pH and relative amount of the dye as a function of the Heparin repeat unit number; formation of a dye/polysaccharide aggregate was studied under the same conditions and structural models of the two types of aggregates were proposed. As a consequence of such an investigation a new Heparin determination methodology was developed.

Antibiotic therapies to eradicate medical device-associated infections often fail because of the ability of sessile bacteria, encased in their exopolysaccharide matrix, to be more drug resistant than planktonic organisms. In the last two decades, several strategies to prevent microbial adhesion and biofilm formation on the surfaces of medical devices, based mainly on the use of antiadhesive, antiseptic, and antibiotic coatings on polymer surfaces, have been developed. More recent alternative approaches are based on molecules able to interfere with quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified β- N -acetylglucosaminidase, dispersin B, produced by the gram-negative periodontal pathogen Actinobacillus actinomycetemcomitans , is able to dissolve mature biofilms produced by Staphylococcus epidermidis as well as some other bacterial species. Therefore, in this study, we developed new polymeric matrices able to bind dispersin B either alone or in combination with an antibiotic molecule, cefamandole nafate (CEF). We showed that our functionalized polyurethanes could adsorb a significant amount of dispersin B, which was able to exert its hydrolytic activity against the exopolysaccharide matrix produced by staphylococcal strains. When microbial biofilms were exposed to both dispersin B and CEF, a synergistic action became evident, thus characterizing these polymer-dispersin B-antibiotic systems as promising, highly effective tools for preventing bacterial colonization of medical devices.

Central venous catheters are a major cause of nosocomial bloodstream infections. Different attempts have been made to incorporate antimicrobial agents into catheters, particularly directed at the surface-coating of devices. To facilitate the antimicrobial adsorption, various cationic surfactants, which however showed several problems, have been used. On the other hand, impregnated catheters with only antimicrobials have demonstrated a short-term duration due to the difficulties to deliver the drug slowly. Thus, in order to obtain high antimicrobial-polymer affinity we synthesized or modified polyurethanes to introduce different functional groups. Polymers were loaded with two antibiotics, cefamandole nafate and rifampin (RIF), chosen for both their functional groups and their action spectrum. The in vitro release behavior showed that the elution of drugs depended on the matrix hydrophilicity and on the antibiotic-polymer and antibiotic-antibiotic interactions. To increase the amount of drug released, polyethylene glycol (PEG) used as a pore forming agent at different molecular weights was incorporated in the polymer bulk with antibiotics. As for the in vitro antimicrobial activity of matrices, assessed by Kirby-Bauer test, it was seen that antibiotics released from various formulations inhibited the bacterial growth and exerted a synergistic effect when both were present. In particular, PEG10000-containing polymer was active against the RIF-resistant S. aureus strain up to 23 days. These results suggest that the combined entrapping of antibiotics and pore formers in these novel polymer systems could be promising to prevent the bacterial colonization and to control the emergence of bacterial resistance.

The accumulation of reactive oxygen species (ROS) in microbial biofilms has been recently recognized to play a role in promoting antibiotic resistance in biofilm-growing bacteria. ROS are also over-produced when a medical device is implanted and they can promote device susceptibility to infection or aseptic loosening. High levels of ROS seem also to be responsible for the establishment of chronic wounds.In this study, a novel antioxidant polyacrylate was synthesized and investigated in terms of antimicrobial and antibiofilm activity. The polymer possesses in side-chain hydroxytyrosol (HTy), that is a polyphenolic compound extracted from olive oil wastewaters.The obtained 60 nm in size polymer nanoparticles showed good scavenging and antibacterial activity versus a strain of Staphylococcus epidermidis. Microbial adherence assays evidenced that the hydroxytyrosol-containing polymer was able to significantly reduce bacterial adhesion compared to the control. These findings open novel perspective for a successful use of this antioxidant polymer for the prevention or treatment of biofilm-based infections as those related to medical devices or chronic wounds.

The functionalization of liposomes with glycosylated amphiphiles is an optimal strategy for targeted drug delivery, leading to enhanced efficacy as well as to reduced side effects of drugs. In fact, the presence of natural or synthetic glycolipids in vesicle formulations might increase their specificity toward lectins, a class of non-enzymatic sugar-binding proteins involved in cellular recognition and adhesion. The capability of a new glucosylated synthetic amphiphile to interact with Concanavalin A (Con A), a plant lectin used as model system, was investigated by a synergic experimental and computational approach, both as pure component and in formulation with a natural phospholipid. The comparison of the affinity with Con A of the new glucosylated amphiphile with respect to that of a previously described structural analogue demonstrates that the hydrophilic spacer length controls the exposure of the glucose residue on liposome surface, and consequently the recognition by the lectin.

Paola Di Bonito,1 Linda Petrone,1 Gabriele Casini,2 Iolanda Francolini,2 Maria Grazia Ammendolia,3 Luisa Accardi,1 Antonella Piozzi,2 Lucio D’Ilario,2 Andrea Martinelli2 1Department of Infectious, Parasitic and Immune-mediated Diseases, Italian National Institute of Health, 2Department of Chemistry, Sapienza University of Rome, Rome, Italy; 3Department of Technology and Health, Italian National Institute of Health, Rome, Italy Background: Poly(L-lactide) (PLLA) is a biodegradable polymer currently used in many biomedical applications, including the production of resorbable surgical devices, porous scaffolds for tissue engineering, nanoparticles and microparticles for the controlled release of drugs or antigens. The surfaces of lamellar PLLA single crystals (PLLAsc) were provided with amino groups by reaction with a multifunctional amine and used to adsorb an Escherichia coli-produced human papillomavirus (HPV)16-E7 protein to evaluate its possible use in antigen delivery for vaccine development.Methods: PLLA single crystals were made to react with tetraethylenepentamine to obtain amino-functionalized PLLA single crystals (APLLAsc). Pristine and amino-functionalized PLLAsc showed a two-dimensional microsized and one-dimensional nanosized lamellar morphology, with a lateral dimension of about 15–20 µm, a thickness of about 12 nm, and a surface specific area of about 130 m2/g. Both particles were characterized and loaded with HPV16-E7 before being administered to C57BL/6 mice for immunogenicity studies. The E7-specific humoral-mediated and cell-mediated immune response as well as tumor protective immunity were analyzed in mice challenged with TC-1 cancer cells.Results: Pristine and amino-functionalized PLLAsc adsorbed similar amounts of E7 protein, but in protein-release experiments E7-PLLAsc released a higher amount of protein than E7-APLLAsc. When the complexes were dried for observation by scanning electron microscopy, both samples showed a compact layer, but E7-APLLAsc showed greater roughness than E7-PLLAsc. Immunization experiments in mice showed that E7-APLLAsc induced a stronger E7-specific immune response when compared with E7-PLLAsc. Immunoglobulin G isotyping and interferon gamma analysis suggested a mixed Th1/Th2 immune response in both E7-PLLAsc-immunized and E7-APLLAsc-immunized mice. However, only the mice receiving E7-APLLAsc were fully protected from TC-1 tumor growth after three doses of vaccine.Conclusion: Our results show that APLLA single crystals improve the immunogenicity of HPV16-E7 and indicate that E7-APLLAsc could be used for development of an HPV16 therapeutic vaccine against HPV16-related tumors. Keywords: poly(L-lactide), lamellar crystals, human papillomavirus, HPV16-E7, therapeutic vaccine

In this study the ability of chitosan to remove acid, basic, reactive, and direct dyestuffs by adsorption was studied. The effect of several factors influencing dye adsorption such as dye concentration, grain size, pH, and temperature were investigated. Desorption of dyes at different pH was also examined. It was shown that the adsorption capacities of chitosan were comparatively high for acid and direct dyes and that the adsorption was controlled by the acidity of the solution. The kinetics of adsorption were found to be of pseudo second order. Batch isotherm studies showed that adsorption of dyes from aqueous solution by chitosan was described by the Langmuir equation. © , Copyright © Taylor & Francis Group, LLC.